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Zhou H, Gelernter J. Human genetics and epigenetics of alcohol use disorder. J Clin Invest 2024; 134:e172885. [PMID: 39145449 PMCID: PMC11324314 DOI: 10.1172/jci172885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024] Open
Abstract
Alcohol use disorder (AUD) is a prominent contributor to global morbidity and mortality. Its complex etiology involves genetics, epigenetics, and environmental factors. We review progress in understanding the genetics and epigenetics of AUD, summarizing the key findings. Advancements in technology over the decades have elevated research from early candidate gene studies to present-day genome-wide scans, unveiling numerous genetic and epigenetic risk factors for AUD. The latest GWAS on more than one million participants identified more than 100 genetic variants, and the largest epigenome-wide association studies (EWAS) in blood and brain samples have revealed tissue-specific epigenetic changes. Downstream analyses revealed enriched pathways, genetic correlations with other traits, transcriptome-wide association in brain tissues, and drug-gene interactions for AUD. We also discuss limitations and future directions, including increasing the power of GWAS and EWAS studies as well as expanding the diversity of populations included in these analyses. Larger samples, novel technologies, and analytic approaches are essential; these include whole-genome sequencing, multiomics, single-cell sequencing, spatial transcriptomics, deep-learning prediction of variant function, and integrated methods for disease risk prediction.
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Affiliation(s)
- Hang Zhou
- Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
- Department of Biomedical Informatics and Data Science
- Center for Brain and Mind Health
| | - Joel Gelernter
- Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA
- Department of Genetics, and
- Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, USA
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Kang B, Kim C, Shin SH, Shin H, Cho Y. Impact of Alcohol-Induced Facial Flushing Phenotype on Alcohol Consumption Among Korean Adults: 2-Year Cross-Sectional Study. JMIR Public Health Surveill 2024; 10:e49826. [PMID: 38796304 PMCID: PMC11325126 DOI: 10.2196/49826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 04/29/2024] [Accepted: 05/23/2024] [Indexed: 05/28/2024] Open
Abstract
BACKGROUND The alcohol-induced facial flushing phenotype (flushing) is common among East Asians. Despite a small intake of alcohol, they experience heightened levels of acetaldehyde, a group-1 carcinogen, which, in turn, causes unpleasant symptoms such as redness, acting as a robust protective mechanism against consuming alcohol. However, some individuals with this genetic trait exhibit weakened alcohol restraint, which increases the risk of developing alcohol-related cancers, such as esophageal and head or neck cancer, by several times. Although this flushing phenomenon is crucial for public health, there is a paucity of studies that have comprehensively investigated the effect of flushing or its genotype on alcohol consumption in a large group of East Asians while controlling for various sociodemographic and health-related variables at a country level. OBJECTIVE This 2-year cross-sectional study aims to explore the effect of flushing on drinking behavior in Koreans and to examine whether the effect varies across sociodemographic and health-related factors. METHODS We used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for 2019 and 2020 conducted by the Korea Disease Control and Prevention Agency. Our sample comprised 10,660 Korean adults. The study investigated the association of 26 variables, including flushing, with drinking frequency and amount. The effect of flushing was examined with and without adjusting for the other 25 variables using multinomial logistic regression analysis. In addition, we tested the interaction effect with flushing and conducted a simple effect analysis. We used complex sample design elements, including strata, clusters, and weights, to obtain unbiased results for the Rao-Scott χ2 test, 2-tailed t test, and multinomial logistic regression analysis. RESULTS The suppressive effect of flushing was significant (P<.001) across all pronounced categories of alcohol consumption in 2019. The ranges of standardized regression slopes and odds ratios (ORs) were -6.70≥β≥-11.25 and 0.78≥OR≥0.50 for frequency and -5.37≥β≥-17.64 and 0.73≥OR≥0.36 for amount, respectively. The effect became somewhat stronger when adjusted for confounders. The effect also exhibited an overall stronger trend as the severity of alcohol consumption increased. The β values and ORs were consistently smaller in 2020 compared to the previous year. A simple effect analysis revealed a diminished alcohol-suppressive effect of flushing on alcohol consumption for specific groups (eg, those with low levels of education, limited family support, physical labor, or health-related issues). CONCLUSIONS Our findings suggest that flushing suppresses drinking in Koreans overall but has little or no effect in certain susceptible populations. Therefore, health authorities should conduct targeted epidemiological studies to assess drinking patterns and disease profiles, particularly regarding alcohol-related cancers, and establish effective preventive measures tailored to this population.
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Affiliation(s)
- Bossng Kang
- Department of Emergency Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Changsun Kim
- Department of Emergency Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Seon-Hi Shin
- Biostatistical Consulting and Research Lab, Medical Research Collaborating Center, Hanyang University, Seoul, Republic of Korea
| | - Hyungoo Shin
- Department of Emergency Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Yongil Cho
- Department of Emergency Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
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Trang KB, Chesi A, Toikumo S, Pippin JA, Pahl MC, O’Brien JM, Amundadottir LT, Brown KM, Yang W, Welles J, Santoleri D, Titchenell PM, Seale P, Zemel BS, Wagley Y, Hankenson KD, Kaestner KH, Anderson SA, Kayser MS, Wells AD, Kranzler HR, Kember RL, Grant SF. Shared and unique 3D genomic features of substance use disorders across multiple cell types. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.07.18.24310649. [PMID: 39072016 PMCID: PMC11275669 DOI: 10.1101/2024.07.18.24310649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Recent genome-wide association studies (GWAS) have revealed shared genetic components among alcohol, opioid, tobacco and cannabis use disorders. However, the extent of the underlying shared causal variants and effector genes, along with their cellular context, remain unclear. We leveraged our existing 3D genomic datasets comprising high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq and RNA-seq across >50 diverse human cell types to focus on genomic regions that coincide with GWAS loci. Using stratified LD regression, we determined the proportion of genomewide SNP heritability attributable to the features assayed across our cell types by integrating recent GWAS summary statistics for the relevant traits: alcohol use disorder (AUD), tobacco use disorder (TUD), opioid use disorder (OUD) and cannabis use disorder (CanUD). Statistically significant enrichments (P<0.05) were observed in 14 specific cell types, with heritability reaching 9.2-fold for iPSC-derived cortical neurons and neural progenitors, confirming that they are crucial cell types for further functional exploration. Additionally, several pancreatic cell types, notably pancreatic beta cells, showed enrichment for TUD, with heritability enrichments up to 4.8-fold, suggesting genomic overlap with metabolic processes. Further investigation revealed significant positive genetic correlations between T2D with both TUD and CanUD (FDR<0.05) and a significant negative genetic correlation with AUD. Interestingly, after partitioning the heritability for each cell type's cis-regulatory elements, the correlation between T2D and TUD for pancreatic beta cells was greater (r=0.2) than the global genetic correlation value. Our study provides new genomic insights into substance use disorders and implicates cell types where functional follow-up studies could reveal causal variant-gene mechanisms underpinning these disorders.
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Affiliation(s)
- Khanh B. Trang
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Alessandra Chesi
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sylvanus Toikumo
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - James A. Pippin
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Matthew C. Pahl
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Joan M. O’Brien
- Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA, USA
- Penn Medicine Center for Ophthalmic Genetics in Complex Disease, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA, USA
| | - Laufey T. Amundadottir
- Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Kevin M. Brown
- Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Wenli Yang
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jaclyn Welles
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Dominic Santoleri
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Paul M. Titchenell
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Patrick Seale
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Babette S. Zemel
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, PA, USA
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Yadav Wagley
- Department of Orthopedic Surgery, University of Michigan Medical School Ann Arbor, MI, USA
| | - Kurt D. Hankenson
- Department of Orthopedic Surgery, University of Michigan Medical School Ann Arbor, MI, USA
| | - Klaus H. Kaestner
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Stewart A. Anderson
- Department of Child and Adolescent Psychiatry, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Matthew S. Kayser
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Chronobiology Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Andrew D. Wells
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Henry R. Kranzler
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rachel L. Kember
- Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Struan F.A. Grant
- Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
- Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
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Faniyan OO, Marcotulli D, Simayi R, Del Gallo F, De Carlo S, Ficiarà E, Caramaschi D, Richmond R, Franchini D, Bellesi M, Ciccocioppo R, de Vivo L. Adolescent chronic sleep restriction promotes alcohol drinking in adulthood: evidence from epidemiological and preclinical data. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.10.11.561858. [PMID: 38659740 PMCID: PMC11042206 DOI: 10.1101/2023.10.11.561858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
Epidemiological investigations have indicated that insufficient sleep is prevalent among adolescents, posing a globally underestimated health risk. Sleep fragmentation and sleep loss during adolescence have been linked to concurrent emotional dysregulation and an increase in impulsive, risk-taking behaviors, including a higher likelihood of substance abuse. Among the most widely used substances, alcohol stands as the primary risk factor for deaths and disability among individuals aged 15-49 worldwide. While the association between sleep loss and alcohol consumption during adolescence is well documented, the extent to which prior exposure to sleep loss in adolescence contributes to heightened alcohol use later in adulthood remains less clearly delineated. Here, we analyzed longitudinal epidemiological data spanning 9 years, from adolescence to adulthood, including 5497 participants of the Avon Longitudinal Study of Parents And Children cohort. Sleep and alcohol measures collected from interviews and questionnaires at 15 and 24 years of age were analyzed with multivariable linear regression and a cross-lagged autoregressive path model. Additionally, we employed a controlled preclinical experimental setting to investigate the causal relationship underlying the associations found in the human study and to assess comorbid behavioral alterations. Preclinical data were collected by sleep restricting Marchigian Sardinian alcohol preferring rats (msP, n=40) during adolescence and measuring voluntary alcohol drinking concurrently and in adulthood. Polysomnography was used to validate the efficacy of the sleep restriction procedure. Behavioral tests were used to assess anxiety, risky behavior, and despair. In humans, after adjusting for covariates, we found a cross-sectional association between all sleep parameters and alcohol consumption at 15 years of age but not at 24 years. Notably, alcohol consumption (Alcohol Use Disorder Identification Test for Consumption) at 24 years was predicted by insufficient sleep at 15 years whilst alcohol drinking at 15 years could not predict sleep problems at 24. In msP rats, adolescent chronic sleep restriction escalated alcohol consumption and led to increased propensity for risk-taking behavior in adolescence and adulthood. Our findings demonstrate that adolescent insufficient sleep causally contributes to higher adult alcohol consumption, potentially by promoting risky behavior.
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Affiliation(s)
- Oluwatomisin O. Faniyan
- International School of Advanced Studies, University of Camerino, 62032 Camerino (MC), Italy
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Daniele Marcotulli
- Department of Sciences of Public Health and Pediatrics, University of Torino, 10126 Turin, Italy
| | - Reyila Simayi
- International School of Advanced Studies, University of Camerino, 62032 Camerino (MC), Italy
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Federico Del Gallo
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Sara De Carlo
- International School of Advanced Studies, University of Camerino, 62032 Camerino (MC), Italy
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Eleonora Ficiarà
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Doretta Caramaschi
- Faculty of Health and Life Sciences, Department of Psychology, University of Exeter, Washington Singer Laboratories, Perry Road, Exeter EX4 4QG, UK
| | - Rebecca Richmond
- Bristol Medical School, Bristol Population Health Science Institute, University of Bristol, BS8 2BN Bristol, UK
| | - Daniela Franchini
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, BS8 1TD Bristol, UK
| | - Michele Bellesi
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, BS8 1TD Bristol, UK
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Roberto Ciccocioppo
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
| | - Luisa de Vivo
- School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy
- Center for Neuroscience, University of Camerino, 62032 Camerino (MC), Italy
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Han MJ, Kim ST, Park CI, Hwang SS, Kim HW, Kang JI, Kim SJ. Serial mediating effects of childhood trauma and conduct behaviors on the impact of family history among patients with alcohol use disorder. Sci Rep 2024; 14:7196. [PMID: 38532019 DOI: 10.1038/s41598-024-57861-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/22/2024] [Indexed: 03/28/2024] Open
Abstract
Family history (FH) of alcoholism increases the risk of alcohol use disorder (AUD); however, the contribution of childhood trauma (CT) in this respect remains unclear. This study investigated the relationship between FH and AUD-related clinical characteristics (social onset, antisocial tendency, and severity of problematic alcohol consumption) through the mediating effects of childhood trauma (CT) and conduct behaviors (CB) in a Korean male population with AUD. A total of 304 patients hospitalized for AUD at 16 psychiatric hospitals completed standardized questionnaires, including self-rated scales. Mediation analyses were performed using the SPSS macro PROCESS. Individuals with positive FH (133, 44%) had greater CT and CB and more severe AUD-related clinical characteristics than those without FH (171, 56%). In the present serial mediation model, FH had significant direct and indirect effects on AUD-related clinical characteristics through CT and CB. Indirect effects were 21.3% for social onset, 46.3%, antisocial tendency, and 37.9% for problematic drinking. FH directly contributed to AUD-related clinical characteristics, and CT and CB played mediating roles. This highlights the importance of careful intervention and surveillance of adverse childhood experiences and conduct disorder to prevent and mitigate alcohol-related problems in individuals with FH of AUD.
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Affiliation(s)
- Min Jeong Han
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Shin Tae Kim
- Graduate School, Yonsei University College of Medicine, Seoul, South Korea
| | - Chun Il Park
- Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
| | - Syung Shick Hwang
- Graduate School, Yonsei University College of Medicine, Seoul, South Korea
| | - Hae Won Kim
- Department of Medical Education, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jee In Kang
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
- Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea.
| | - Se Joo Kim
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
- Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea.
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Lai D, Kuo SIC, Wetherill L, Aliev F, Zhang M, Abreu M, Schwantes-An TH, Dick D, Francis MW, Johnson EC, Kamarajan C, Kinreich S, Kuperman S, Meyers J, Nurnberger JI, Liu Y, Edenberg HJ, Porjesz B, Agrawal A, Foroud T, Schuckit M, Plawecki MH, Bucholz KK, McCutcheon VV. Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:283-294. [PMID: 38054532 PMCID: PMC10922306 DOI: 10.1111/acer.15239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/29/2023] [Accepted: 11/29/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. METHODS Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. RESULTS In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, βs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, β = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, β = 0.15). CONCLUSIONS PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.
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Affiliation(s)
- Dongbing Lai
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Sally I-Chun Kuo
- Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ
| | - Leah Wetherill
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Fazil Aliev
- Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ
| | - Michael Zhang
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Marco Abreu
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Tae-Hwi Schwantes-An
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Danielle Dick
- Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ
| | | | - Emma C. Johnson
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO
| | - Chella Kamarajan
- Henri Begleiter Neurodynamics Lab, Department of Psychiatry, SUNY Downstate Health Science University, NY
| | - Sivan Kinreich
- Henri Begleiter Neurodynamics Lab, Department of Psychiatry, SUNY Downstate Health Science University, NY
| | - Samuel Kuperman
- Department of Psychiatry, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA
| | - Jacquelyn Meyers
- Henri Begleiter Neurodynamics Lab, Department of Psychiatry, SUNY Downstate Health Science University, NY
| | - John I Nurnberger
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN
| | - Yunlong Liu
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Howard J Edenberg
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
| | - Bernice Porjesz
- Henri Begleiter Neurodynamics Lab, Department of Psychiatry, SUNY Downstate Health Science University, NY
| | - Arpana Agrawal
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO
| | - Tatiana Foroud
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Marc Schuckit
- Department of Psychiatry, University of California, San Diego Medical School, San Diego, CA
| | - Martin H. Plawecki
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN
| | - Kathleen K. Bucholz
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO
| | - Vivia V. McCutcheon
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO
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Zheng Q, Wang H, Yan A, Yin F, Qiao X. DNA Methylation in Alcohol Use Disorder. Int J Mol Sci 2023; 24:10130. [PMID: 37373281 DOI: 10.3390/ijms241210130] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Excessive drinking damages the central nervous system of individuals and can even cause alcohol use disorder (AUD). AUD is regulated by both genetic and environmental factors. Genes determine susceptibility to alcohol, and the dysregulation of epigenome drives the abnormal transcription program and promotes the occurrence and development of AUD. DNA methylation is one of the earliest and most widely studied epigenetic mechanisms that can be inherited stably. In ontogeny, DNA methylation pattern is a dynamic process, showing differences and characteristics at different stages. DNA dysmethylation is prevalent in human cancer and alcohol-related psychiatric disorders, resulting in local hypermethylation and transcriptional silencing of related genes. Here, we summarize recent findings on the roles and regulatory mechanisms of DNA methylation, the development of methyltransferase inhibitors, methylation alteration during alcohol exposure at different stages of life, and possible therapeutic options for targeting methylation in human and animal studies.
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Affiliation(s)
- Qingmeng Zheng
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Heng Wang
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - An Yan
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Fangyuan Yin
- School of Medicine, College of Forensic Science, Xi'an Jiaotong University, Xi'an 710061, China
| | - Xiaomeng Qiao
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
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Gentry AE, Alexander JC, Ahangari M, Peterson RE, Miles MF, Bettinger JC, Davies AG, Groteweil M, Bacanu SA, Kendler KS, Riley BP, Webb BT. Case-only exome variation analysis of severe alcohol dependence using a multivariate hierarchical gene clustering approach. PLoS One 2023; 18:e0283985. [PMID: 37098020 PMCID: PMC10128939 DOI: 10.1371/journal.pone.0283985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/21/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Variation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria. OBJECTIVE Leverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes. METHODS First, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively. RESULTS Three non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated. CONCLUSION The proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence.
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Affiliation(s)
- Amanda Elswick Gentry
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Jeffry C. Alexander
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Mohammad Ahangari
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Integrative Life Sciences Ph.D. Program, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Roseann E. Peterson
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry and Behavioral Sciences, Institute for Genomics in Health, SUNY Downstate Health Sciences University, Brooklyn, New York, United States of America
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Michael F. Miles
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Jill C. Bettinger
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Andrew G. Davies
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Mike Groteweil
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Silviu A. Bacanu
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Kenneth S. Kendler
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Brien P. Riley
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Bradley T. Webb
- VCU Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States of America
- GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Caroline, United States of America
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9
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Netope RN, Nghitanwa EM, Endjala T. Investigation of the determinants of alcohol use among women in Oshikoto region, Namibia. J Public Health Afr 2023; 14:2241. [PMID: 37197260 PMCID: PMC10184179 DOI: 10.4081/jphia.2023.2241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 07/03/2022] [Indexed: 05/19/2023] Open
Abstract
Background Alcohol abuse is one of the world's main public health issues. Alcohol use is growing among African women, and it has become an underlying factor in women's health risk profiles. Objective The purpose of this study is to investigate the factors that influence women's alcohol consumption in the Oshikoto Region. Materials and Methods The study used a quantitative research method with a cross-sectional, analytical design. Data were gathered using interview-led questionnaires from 121 women aged 18-49 years at two state hospitals in the Oshikoto region's two selected constituencies. The Statistical Package for the Social Sciences, version 26, was used to evaluate the data. Results The subjects' median age was 33 years old. The bulk of the participants, 84 (69.4%), resided in rural areas. 49 (40.5%) of the participants were unmarried, and the majority (62%) had children. According to the results, 64 (52.89%) of respondents use alcohol to cope with their problems on occasion. When they are anxious, approximately 56 (46.28%) of the respondents use alcohol to relax and ignore their problems. In the univariable log-binomial regression analysis, a family history of alcohol use (p-value 0.019), peer pressure (p-value 0.004), and spending the majority of time at Cuca shops (p-value 0.000) were all linked with an increased risk of harmful alcohol use. Conclusion Identifying the determinants of alcohol use may aid in the creation of recommendations for preventative measures and alcohol awareness programs.
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Affiliation(s)
| | - Emma Maano Nghitanwa
- School of Nursing and Public Health, University of Namibia, P/Bag 13301, Windhoek, Namibia.
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10
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Scholl JL, King ZR, Pearson K, Kallsen NA, Ehli EA, Fercho KA, Brown-Rice KA, Forster GL, Baugh LA. Methylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents. Brain Behav Immun Health 2022; 25:100505. [PMID: 36110145 PMCID: PMC9468507 DOI: 10.1016/j.bbih.2022.100505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 10/31/2022] Open
Abstract
Many Americans are adult children of an alcoholic parent (ACoA), which can confer an increased risk of trauma and hazardous alcohol use, as well as heritable and environmental genetic influence. Psychological health and related neural activity can be influenced by inflammation responses, but it is not clear how these factors interact regarding risk or resilience to hazardous alcohol use. The goals of this study were to better understand the relationships between current alcohol use and inflammation, how these are modified by single nucleotide polymorphisms (SNPs) and/or epigenetic modifications of inflammation-associated genes; and how these alter neural reactivity to emotionally-salient stimuli. To do so, ACoA participants were dichotomized as resilient (not engaged in hazardous alcohol use) or vulnerable (currently engaged in hazardous alcohol use). Measures of blood-oxygen-level-dependent (BOLD) activity within regions of interest (ROIs), SNPs and DNA methylation of specific inflammation regulatory genes, and biological markers of inflammation were compared between these groups. Vulnerable ACoAs exhibited higher plasma C-reactive protein (CRP) and greater BOLD activity in the right hippocampus and ventral anterior cingulate cortex in response to emotional cues as well as reduced methylation of CRP and glucocorticoid-related genes. Path analysis revealed significant relationships between alcohol use, SNPs, DNA methylation of inflammatory-related genes, CRP levels, and BOLD activity to emotional stimuli. Taken together, these findings suggest a complex association related to hazardous alcohol use in ACoAs that may predict current inflammation and neural reactivity to emotional stimuli. A better understanding of these associations could direct the future of individual treatment options.
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Affiliation(s)
- Jamie L. Scholl
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | - Zach R. King
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | - Kami Pearson
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
| | | | - Erik A. Ehli
- Avera Institute for Human Genetics, Sioux Falls, SD, USA
| | | | - Kathleen A. Brown-Rice
- Department of Counselor Education, College of Education, Sam Houston State University, Huntsville, TX, USA
| | - Gina L. Forster
- Department of Anatomy, University of Otago, Dunedin, New Zealand
| | - Lee A. Baugh
- Basic Biomedical Sciences & Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, USA
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11
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Guzman DM, Chakka K, Shi T, Marron A, Fiorito AE, Rahman NS, Ro S, Sucich DG, Pierce JT. Transgenerational effects of alcohol on behavioral sensitivity to alcohol in Caenorhabditis elegans. PLoS One 2022; 17:e0271849. [PMID: 36256641 PMCID: PMC9578632 DOI: 10.1371/journal.pone.0271849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 09/29/2022] [Indexed: 11/06/2022] Open
Abstract
Alcohol abuse and dependence have a substantial heritable component. Although the genome has been considered the sole vehicle of heritable phenotypes, recent studies suggest that drug or alcohol exposure may induce alterations in gene expression that are transmitted across generations. Still, the transgenerational impact of alcohol use (and abuse) remains largely unexplored in part because multigenerational studies using rodent models present challenges for time, sample size, and genetic heterogeneity. Here, we took advantage of the extremely short generation time, large broods, and clonal form of reproduction of the nematode Caenorhabditis elegans. We developed a model of pre-fertilization parental alcohol exposure to test alterations in behavioral responses to acute alcohol treatment (referred to in short as intoxication) in subsequent F1, F2 and F3 generations. We found that chronic and intermittent alcohol-treatment paradigms resulted in opposite changes to intoxication sensitivity of F3 progeny that were only apparent when controlling for yoked trials. Chronic alcohol-treatment paradigm in the parental generation resulted in alcohol-naïve F3 progeny displaying moderate resistance to intoxication. Intermittent treatment resulted in alcohol-naïve F3 progeny displaying moderate hypersensitivity to intoxication. Further study of these phenomena using this new C. elegans model may yield mechanistic insights into how transgenerational effects may occur in other animals.
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Affiliation(s)
- Dawn M. Guzman
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Keerthana Chakka
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Ted Shi
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Alyssa Marron
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Ansley E. Fiorito
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Nima S. Rahman
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Stephanie Ro
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
| | - Dylan G. Sucich
- Department of Biology, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Jonathan T. Pierce
- Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, Center for Learning and Memory, University of Texas at Austin, Austin, Texas, United States of America
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12
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Co-Inheritance of Variation in All-Cause Mortality and Biochemical Risk Factors. Twin Res Hum Genet 2022; 25:107-114. [PMID: 35818962 DOI: 10.1017/thg.2022.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Biomarkers may be useful endophenotypes for genetic studies if they share genetic sources of variation with the outcome, for example, with all-cause mortality. Australian adult study participants who had reported their parental survival information were included in the study: 14,169 participants had polygenic risk scores (PRS) from genotyping and up to 13,365 had biomarker results. We assessed associations between participants' biomarker results and parental survival, and between biomarker results and eight parental survival PRS at varying p-value cut-offs. Survival in parents was associated with participants' serum bilirubin, C-reactive protein, HDL cholesterol, triglycerides and uric acid, and with LDL cholesterol for participants' fathers but not for their mothers. PRS for all-cause mortality were associated with liver function tests (alkaline phosphatase, butyrylcholinesterase, gamma-glutamyl transferase), metabolic tests (LDL and HDL cholesterol, triglycerides, uric acid), and acute-phase reactants (C-reactive protein, globulins). Association between offspring biomarker results and parental survival demonstrates the existence of familial effects common to both, while associations between biomarker results and PRS for mortality favor at least a partial genetic cause of this covariation. Identification of genetic loci affecting mortality-associated biomarkers offers a route to the identification of additional loci affecting mortality.
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13
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Tsermpini EE, Goričar K, Kores Plesničar B, Plemenitaš Ilješ A, Dolžan V. Genetic Variability of Incretin Receptors and Alcohol Dependence: A Pilot Study. Front Mol Neurosci 2022; 15:908948. [PMID: 35754710 PMCID: PMC9218814 DOI: 10.3389/fnmol.2022.908948] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/09/2022] [Indexed: 11/13/2022] Open
Abstract
Alcohol dependence is a chronic mental disorder that leads to decreased quality of life for patients and their relatives and presents a considerable burden to society. Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are endogenous gut-brain peptides, which can travel across the blood-brain barrier and access the nervous system. Their respective receptors, GIPR and GLP-1R, are expressed in the reward-related brain areas and are involved in memory formation and neurogenesis, which results in behavioral changes in rodent models. The current study investigated the potential association of genetic variability of incretin receptors with alcohol dependence and alcohol-related psychosymptomatology. Alcohol dependence and comorbid psychosymptomatology were assessed in a cohort of Slovenian male participants, comprised of 89 hospitalized alcohol-dependent patients, 98 abstinent alcohol-dependent patients, and 93 healthy blood donors. All participants were genotyped for GIPR rs1800437 and GLP1R rs10305420 and rs6923761 polymorphisms. For the statistical analysis Kruskal-Wall and Mann-Whitney tests were used in additive and dominant genetic models. Our findings indicated that GIPR rs1800437 genotypes were associated with an increased risk of alcohol dependence. Statistically significant association between GIPR rs1800437 GG genotype and Brief Social Phobia Scale scores were observed in the abstinent alcohol-dependent patients, while GLP1R rs6923761 GG genotype was associated with Zung anxiety scores in healthy controls. Our pilot study indicates that GIPR rs1800437 may play some role in susceptibility to alcohol dependence, as well as in alcohol-related psychosymptomatology symptoms. To our knowledge, this is the first study that indicates the involvement of GIPR in alcohol dependence. However, studies with larger cohorts are needed to confirm these preliminary findings.
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Affiliation(s)
- Evangelia Eirini Tsermpini
- Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Katja Goričar
- Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Blanka Kores Plesničar
- University Psychiatric Clinic, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | - Vita Dolžan
- Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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14
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Kaya-Akyüzlü D, Özkan-Kotiloğlu S, Yalçın-Şahiner Ş, Ağtaş-Ertan E, Özgür-İlhan İ. Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use. Eur J Pharmacol 2022; 921:174862. [PMID: 35271823 DOI: 10.1016/j.ejphar.2022.174862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 02/17/2022] [Accepted: 02/22/2022] [Indexed: 11/03/2022]
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15
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Yang JJ, Luo X, Trucco EM, Buu A. Polygenic risk prediction based on singular value decomposition with applications to alcohol use disorder. BMC Bioinformatics 2022; 23:28. [PMID: 35012447 PMCID: PMC8744290 DOI: 10.1186/s12859-022-04566-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIM The polygenic risk score (PRS) shows promise as a potentially effective approach to summarize genetic risk for complex diseases such as alcohol use disorder that is influenced by a combination of multiple variants, each of which has a very small effect. Yet, conventional PRS methods tend to over-adjust confounding factors in the discovery sample and thus have low power to predict the phenotype in the target sample. This study aims to address this important methodological issue. METHODS This study proposed a new method to construct PRS by (1) approximating the polygenic model using a few principal components selected based on eigen-correlation in the discovery data; and (2) conducting principal component projection on the target data. Secondary data analysis was conducted on two large scale databases: the Study of Addiction: Genetics and Environment (SAGE; discovery data) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; target data) to compare performance of the conventional and proposed methods. RESULT AND CONCLUSION The results show that the proposed method has higher prediction power and can handle participants from different ancestry backgrounds. We also provide practical recommendations for setting the linkage disequilibrium (LD) and p value thresholds.
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Affiliation(s)
- James J. Yang
- grid.267308.80000 0000 9206 2401Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, USA
| | - Xi Luo
- grid.267308.80000 0000 9206 2401Department of Biostatistics and Data Science, University of Texas Health Science Center, Houston, USA
| | - Elisa M. Trucco
- grid.65456.340000 0001 2110 1845Department of Psychology, Florida International University, Miami, USA ,grid.214458.e0000000086837370Department of Psychiatry, University of Michigan, Ann Arbor, USA
| | - Anne Buu
- grid.267308.80000 0000 9206 2401Department of Health Promotion and Behavioral Sciences, University of Texas Health Science Center, Houston, USA
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16
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Common Features in Compulsive Sexual Behavior, Substance Use Disorders, Personality, Temperament, and Attachment-A Narrative Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 19:ijerph19010296. [PMID: 35010552 PMCID: PMC8751077 DOI: 10.3390/ijerph19010296] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/24/2021] [Accepted: 12/25/2021] [Indexed: 12/23/2022]
Abstract
Do addictions share common traits of an “addictive personality” or do different addictions have distinct personality profiles? This narrative review examines the differences in the associations between substance use disorder (SUD) and compulsive sexual behavior disorder (CSBD), on the one hand, and personality traits, attachment dispositions, and temperament, on the other hand. We found that both people with a SUD and people with CSBD tended to be more spontaneous, careless, and less reliable, to place self-interest above getting along with others, to show emotional instability and experience negative emotions such as anger, anxiety, and/or depression, to be less able to control their attention and/or behavior, and to be engulfed with a constant sensation of “wanting”. Only people with CSBD, but not SUD, noted concerns with their social ties, fear of losing close others, and/or trusting others around them. Results also suggested that people with a SUD and people with CSBD share high commonalities in personality traits and temperament, yet there are noted differences in their social tendencies, especially with close others. People with CSBD reported more concerns with possible relationship losses compared to people with SUD issues, who may be more worried about losing their source of escapism.
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17
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Smith AJ, Farmer R, Pilarzyk K, Porcher L, Kelly MP. A genetic basis for friendship? Homophily for membrane-associated PDE11A-cAMP-CREB signaling in CA1 of hippocampus dictates mutual social preference in male and female mice. Mol Psychiatry 2021; 26:7107-7117. [PMID: 34321593 PMCID: PMC9583245 DOI: 10.1038/s41380-021-01237-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/25/2021] [Accepted: 07/09/2021] [Indexed: 12/18/2022]
Abstract
Although the physical and mental benefits of friendships are clear, the neurobiological mechanisms driving mutual social preferences are not well understood. Studies in humans suggest friends are more genetically similar, particularly for targets within the 3',5'-cyclic adenosine monophosphate (cAMP) cascade. Unfortunately, human studies can not provide conclusive evidence for such a biological driver of friendship given that other genetically related factors tend to co-segregate with friendship (e.g., geographical proximity). As such, here we use mice under controlled conditions to test the hypothesis that homophily in the cAMP-degrading enzyme phosphodiesterase 11A4 (PDE11A4) can dictate mutual social preference. Using C57BL/6J and BALB/cJ mice in two different behavioral assays, we showed that mice with two intact alleles of Pde11a prefer to interact with Pde11 wild-type (WT) mice of the same genetic background over knockout (KO) mice or novel objects; whereas, Pde11 KO mice prefer to interact with Pde11 KO mice over WT mice or novel objects. This mutual social preference was seen in both adult and adolescent mice, and social preference could be eliminated or artificially elicited by strengthening or weakening PDE11A homodimerization, respectively. Stereotactic delivery of an isolated PDE11A GAF-B domain to the mouse hippocampus revealed the membrane-associated pool of PDE11A-cAMP-CREB signaling specifically within the CA1 subfield of hippocampus is most critical for regulating social preference. Our study here not only identifies PDE11A homophily as a key driver of mutual social preference across the lifespan, it offers a paradigm in which other mechanisms can be identified in a controlled fashion.
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Affiliation(s)
- Abigail J Smith
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Reagan Farmer
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Katy Pilarzyk
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Latarsha Porcher
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Michy P Kelly
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
- Center for Research on Aging, University of Maryland School of Medicine, Baltimore, MD, USA.
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Veerappa A, Pendyala G, Guda C. A systems omics-based approach to decode substance use disorders and neuroadaptations. Neurosci Biobehav Rev 2021; 130:61-80. [PMID: 34411560 PMCID: PMC8511293 DOI: 10.1016/j.neubiorev.2021.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/23/2021] [Accepted: 08/14/2021] [Indexed: 11/15/2022]
Abstract
Substance use disorders (SUDs) are a group of neuropsychiatric conditions manifesting due to excessive dependence on potential drugs of abuse such as psychostimulants, opioids including prescription opioids, alcohol, inhalants, etc. Experimental studies have generated enormous data in the area of SUDs, but outcomes from such data have remained largely fragmented. In this review, we attempt to coalesce these data points providing an important first step towards our understanding of the etiology of SUDs. We propose and describe a 'core addictome' pathway that behaves central to all SUDs. Besides, we also have made some notable observations paving way for several hypotheses; MECP2 behaves as a master switch during substance use; five distinct gene clusters were identified based on respective substance addiction; a central cluster of genes serves as a hub of the addiction pathway connecting all other substance addiction clusters. In addition to describing these findings, we have emphasized the importance of some candidate genes that are of substantial interest for further investigation and serve as high-value targets for translational efforts.
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Affiliation(s)
- Avinash Veerappa
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Gurudutt Pendyala
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Child Health Research Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Chittibabu Guda
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Center for Biomedical Informatics Research and Innovation, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
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Vornholt E, Drake J, Mamdani M, McMichael G, Taylor ZN, Bacanu S, Miles MF, Vladimirov VI. Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges. Addict Biol 2021; 26:e13071. [PMID: 34164896 PMCID: PMC8590811 DOI: 10.1111/adb.13071] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 04/21/2021] [Accepted: 05/31/2021] [Indexed: 12/11/2022]
Abstract
Our lab and others have shown that chronic alcohol use leads to gene and miRNA expression changes across the mesocorticolimbic (MCL) system. Circular RNAs (circRNAs) are noncoding RNAs that form closed-loop structures and are reported to alter gene expression through miRNA sequestration, thus providing a potentially novel neurobiological mechanism for the development of alcohol dependence (AD). Genome-wide expression of circRNA was assessed in the nucleus accumbens (NAc) from 32 AD-matched cases/controls. Significant circRNAs (unadj. p ≤ 0.05) were identified via regression and clustered in circRNA networks via weighted gene co-expression network analysis (WGCNA). CircRNA interactions with previously generated mRNA and miRNA were detected via correlation and bioinformatic analyses. Significant circRNAs (N = 542) clustered in nine significant AD modules (FWER p ≤ 0.05), within which we identified 137 circRNA hubs. We detected 23 significant circRNA-miRNA-mRNA interactions (FDR ≤ 0.10). Among these, circRNA-406742 and miR-1200 significantly interact with the highest number of mRNA, including genes associated with neuronal functioning and alcohol addiction (HRAS, PRKCB, HOMER1, and PCLO). Finally, we integrate genotypic information that revealed 96 significant circRNA expression quantitative trait loci (eQTLs) (unadj. p ≤ 0.002) that showed significant enrichment within recent alcohol use disorder (AUD) and smoking genome-wide association study (GWAS). To our knowledge, this is the first study to examine the role of circRNA in the neuropathology of AD. We show that circRNAs impact mRNA expression by interacting with miRNA in the NAc of AD subjects. More importantly, we provide indirect evidence for the clinical importance of circRNA in the development of AUD by detecting a significant enrichment of our circRNA eQTLs among GWAS of substance abuse.
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Affiliation(s)
- Eric Vornholt
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
- Integrative Life Sciences Doctoral ProgramVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of Genetics and Genomic SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - John Drake
- Department of Psychiatry and Behavioral SciencesTexas A&M UniversityCollege StationTexasUSA
| | - Mohammed Mamdani
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Gowon McMichael
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Zachary N. Taylor
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Silviu‐Alin Bacanu
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of PsychiatryVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Michael F. Miles
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
- VCU‐Alcohol Research CenterVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of Pharmacology and ToxicologyVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of NeurologyVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Vladimir I. Vladimirov
- Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of Genetics and Genomic SciencesIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
- Center for Biomarker Research and Precision MedicineVirginia Commonwealth UniversityRichmondVirginiaUSA
- Department of Physiology & BiophysicsVirginia Commonwealth UniversityRichmondVirginiaUSA
- School of PharmacyVirginia Commonwealth UniversityRichmondVirginiaUSA
- Lieber Institute for Brain DevelopmentJohns Hopkins UniversityBaltimoreMarylandUSA
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20
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Abstract
Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.
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Affiliation(s)
- Joseph D. Deak
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA
| | - Emma C. Johnson
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
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21
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Kapoor M, Chao MJ, Johnson EC, Novikova G, Lai D, Meyers JL, Schulman J, Nurnberger JI, Porjesz B, Liu Y, Foroud T, Edenberg HJ, Marcora E, Agrawal A, Goate A. Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases. Nat Commun 2021; 12:5071. [PMID: 34417470 PMCID: PMC8379159 DOI: 10.1038/s41467-021-25392-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 08/03/2021] [Indexed: 11/27/2022] Open
Abstract
Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.
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Affiliation(s)
- Manav Kapoor
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Michael J Chao
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Emma C Johnson
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - Gloriia Novikova
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Dongbing Lai
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jacquelyn L Meyers
- Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, NY, USA
| | - Jessica Schulman
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - John I Nurnberger
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Bernice Porjesz
- Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, NY, USA
| | - Yunlong Liu
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tatiana Foroud
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Howard J Edenberg
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Edoardo Marcora
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Arpana Agrawal
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - Alison Goate
- Departments of Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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22
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence. Mol Psychiatry 2021; 26:4367-4382. [PMID: 31745236 DOI: 10.1038/s41380-019-0588-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 10/22/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022]
Abstract
Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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23
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Szabó Á, Towers A, Newcombe D, Sheridan J. Alcohol use trajectories across the life course: Influences of childhood predictors and consequences for late-life health. Drug Alcohol Depend 2021; 224:108713. [PMID: 33940326 DOI: 10.1016/j.drugalcdep.2021.108713] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND The cumulative, negative health effects of alcohol consumption are exacerbated in older adulthood. We used a 'life course epidemiology' approach to explore how alcohol use trajectories develop across the lifespan, what early life events influence these trajectories and their associations with late-life health. METHODS Survey data combined with retrospective life course history interviews were collected from 749 non-lifetime alcohol abstainer adults aged 61-81 years (51 % female). Frequency and quantity items of the AUDIT-C assessed alcohol use across each decade of life. Early life factors were childhood socioeconomic status, parental health behaviours, and age of drinking onset. Health outcomes were alcohol-related conditions. RESULTS Latent class growth analysis yielded two life course trajectories for women: consistently infrequent, low quantity drinking (Group 1: 48 %) and increasingly frequent, low quantity drinking (Group 2: 52 %). Men showed three trajectories: consistently infrequent, low quantity drinking (Group 3: 36 %); increasingly frequent, low quantity drinking (Group 4: 51 %); and drinking with increasing frequency and quantity until midlife, after which consumption gradually declined (Group 5: 13 %). Better childhood socioeconomic status was associated with Groups 2 and 4. Later drinking onset was associated with Groups 1 and 3. Parental alcohol misuse, early drinking initiation and childhood socioeconomic adversity were predictive of Group 5. Those in Group 5 were five-to-seven times more likely to have alcohol-related comorbidities. CONCLUSIONS Early life experiences influence life course hazardous alcohol use. Interventions across the life course, from childhood, when drinking may be initiated, through to older adulthood, when sensitivity to alcohol increases, are needed.
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Affiliation(s)
- Ágnes Szabó
- School of Health Sciences, Massey University, New Zealand; School of Health, Victoria University of Wellington, New Zealand.
| | - Andy Towers
- School of Health Sciences, Massey University, New Zealand
| | - David Newcombe
- Centre for Addiction Research, Faculty of Medical and Health Sciences, the University of Auckland, New Zealand; School of Population Health, Faculty of Medical and Health Sciences, the University of Auckland, New Zealand
| | - Janie Sheridan
- Centre for Addiction Research, Faculty of Medical and Health Sciences, the University of Auckland, New Zealand; School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, New Zealand
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24
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Szentkereszty-Kovács Z, Gáspár K, Szegedi A, Kemény L, Kovács D, Törőcsik D. Alcohol in Psoriasis-From Bench to Bedside. Int J Mol Sci 2021; 22:ijms22094987. [PMID: 34067223 PMCID: PMC8125812 DOI: 10.3390/ijms22094987] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/02/2021] [Accepted: 05/03/2021] [Indexed: 01/22/2023] Open
Abstract
Alcohol affects the symptoms, compliance and comorbidities as well as the safety and efficacy of treatments in psoriatic patients. In this review, we aim to summarize and link clinical observations with a molecular background, such as signaling pathways at the cellular level and genetic variations, and to provide an overview of how this knowledge could influence our treatment selection and patient management.
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Affiliation(s)
- Zita Szentkereszty-Kovács
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary; (Z.S.-K.); (K.G.); (A.S.); (D.K.)
| | - Krisztián Gáspár
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary; (Z.S.-K.); (K.G.); (A.S.); (D.K.)
- Division of Dermatological Allergology, Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary
| | - Andrea Szegedi
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary; (Z.S.-K.); (K.G.); (A.S.); (D.K.)
- Division of Dermatological Allergology, Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary
| | - Lajos Kemény
- HCEMM-USZ Skin Research Group, Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6720 Szeged, Hungary;
- MTA-SZTE Dermatological Research Group, Eötvös Loránd Research Network (ELKH), Korányi fasor 6, 6720 Szeged, Hungary
| | - Dóra Kovács
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary; (Z.S.-K.); (K.G.); (A.S.); (D.K.)
| | - Dániel Törőcsik
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary; (Z.S.-K.); (K.G.); (A.S.); (D.K.)
- Correspondence: ; Tel.: +36-52-255-602
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25
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Dash GF, Martin NG, Agrawal A, Lynskey MT, Slutske WS. Typologies of illicit drug use in mid-adulthood: a quasi-longitudinal latent class analysis in a community-based sample of twins. Addiction 2021; 116:1101-1112. [PMID: 33463859 PMCID: PMC7882637 DOI: 10.1111/add.15225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 04/15/2020] [Accepted: 08/12/2020] [Indexed: 01/04/2023]
Abstract
AIMS To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued ("desistant") and persistent drug use on drug use correlates. DESIGN Latent class analysis was applied to data from a cross-sectional self-report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes. SETTING Computer-assisted telephone interview in respondents' homes. PARTICIPANTS A total of 3785 individual twins and siblings (1365 men, 2420 women; Mage = 32) from the Australian Twin Registry Cohort III. MEASUREMENTS A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality. FINDINGS A five-class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30-0.35) than dizygotic pairs (same-sex k = 0.19-0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a2 = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14-28.01), younger first substance use (OR = 0.82-0.83), more drug use opportunity (OR = 10.66-66.06), and more drug-using peers (OR = 4.66-9.20). CONCLUSIONS Unique patterns of declined/discontinued ("desistant") and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes.
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Affiliation(s)
- Genevieve F. Dash
- University of Missouri, Department of Psychological Sciences, Columbia, MO, 65211, USA
| | | | - Arpana Agrawal
- Washington University School of Medicine, St. Louis, MO, 63110, USA
| | | | - Wendy S. Slutske
- University of Missouri, Department of Psychological Sciences, Columbia, MO, 65211, USA
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26
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Pinheiro-da-Silva J, Araujo-Silva H, Luchiari AC. Does early ethanol exposure increase seeking-like behavior in zebrafish? Int J Dev Neurosci 2021; 81:416-427. [PMID: 33837569 DOI: 10.1002/jdn.10112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/16/2021] [Accepted: 04/05/2021] [Indexed: 01/22/2023] Open
Abstract
Fetal alcohol spectrum disorder (FASD) is the most common cause of birth defects. The severe variations are in fetal alcohol syndrome (FAS) but the most frequent cases are alcohol-related neurodevelopmental disorder (ARND), which is of a difficult diagnosis. ARND characteristics include impaired social behavior, anxiety and depression prevalence, cognitive deficits, and an increased chance for drug addiction. Here, we aimed to test whether early alcohol exposure leads to later alcohol preference. We hypothesize that early alcohol exposure increases the reinforcing effects on later experiences, raising the chance of addiction in adult life. Lately, the zebrafish has been a valuable model on alcohol research, allowing embryonic exposure and the study of the ontogenetic effects. For this, embryos were exposed to three different alcohol treatments: 0.0%, 0.25% and 0.5%, for 2 hr, at 24-hr post-fertilization. Then we evaluated the effects of embryonic alcohol exposure on conditioned place preference in two developmental stage: fry (10 days post-fertilization (dpf)) and young (90 dpf) zebrafish. Results show that control fish presented alcohol associative learning, which means, changes in place preference due to alcohol exposure, at both ontogenetic phases. However, zebrafish exposed to 0.25 and 0.5% alcohol during embryogenesis did not show conditioning response at any evaluated stage. These results suggest perception and cognitive deficits due to embryonic alcohol exposure that can alter alcohol responsiveness throughout a lifetime. Although low alcohol doses do not provoke malformation, it has been shown to induce several neurological and behavioral changes that are termed as Alcohol-Related Neurodevelopmental Disorders. These results may contribute to future investigations on how embryonic exposure affects the neurocircuitry related to perception and associative learning processing.
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Affiliation(s)
| | - Heloysa Araujo-Silva
- Departamento de Fisiologia e Comportamento, Universidade Federal do Rio Grande do Norte, Natal, Brazil
| | - Ana Carolina Luchiari
- Departamento de Fisiologia e Comportamento, Universidade Federal do Rio Grande do Norte, Natal, Brazil
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27
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Bagley JR, Chesler EJ, Philip VM, Jentsch JD. Heritability of ethanol consumption and pharmacokinetics in a genetically diverse panel of collaborative cross mouse strains and their inbred founders. Alcohol Clin Exp Res 2021; 45:697-708. [PMID: 33619752 PMCID: PMC8441258 DOI: 10.1111/acer.14582] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 02/06/2021] [Accepted: 02/12/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Interindividual variation in voluntary ethanol consumption and ethanol response is partially influenced by genetic variation. Discovery of the genes and allelic variants that affect these phenotypes may clarify the etiology and pathophysiology of problematic alcohol use, including alcohol use disorder. Genetically diverse mouse populations, which demonstrate heritable variation in ethanol consumption, can be utilized to discover the genes and gene networks that influence this trait. The Collaborative Cross (CC) recombinant inbred strains, Diversity Outbred (DO) population and their 8 founder strains are complementary mouse resources that capture substantial genetic diversity and can demonstrate expansive phenotypic variation in heritable traits. These populations may be utilized to discover candidate genes and gene networks that moderate ethanol consumption and other ethanol-related traits. METHODS We characterized ethanol consumption, preference, and pharmacokinetics in the 8 founder strains and 10 CC strains in 12-hour drinking sessions during the dark phase of the circadian cycle. RESULTS Ethanol consumption was substantially heritable, both early in ethanol access and over a chronic intermittent access schedule. Ethanol pharmacokinetics were also heritable; however, no association between strain-level ethanol consumption and pharmacokinetics was detected. The PWK/PhJ strain was the highest drinking strain, with consumption substantially exceeding that of the C57BL/6J strain, which is commonly used as a model of "high" or "binge" drinking. Notably, we found strong evidence that sex moderated genetic effects on voluntary ethanol drinking. CONCLUSIONS Collectively, this research serves as a foundation for expanded genetic study of ethanol consumption in the CC/DO and related populations. Moreover, we identified reference strains with extreme consumption phenotypes that effectively represent polygenic models of excessive ethanol use.
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Affiliation(s)
- Jared R Bagley
- Department of Psychology, Binghamton University, Binghamton, NY, USA
| | - Elissa J Chesler
- The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA
| | - Vivek M Philip
- The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA
| | - James D Jentsch
- Department of Psychology, Binghamton University, Binghamton, NY, USA
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28
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Rai V, Kumar P. Methylenetetrahydrofolate reductase ( MTHFR) gene C677T (rs1801133) polymorphism and risk of alcohol dependence: a meta-analysis. AIMS Neurosci 2021; 8:212-225. [PMID: 33709025 PMCID: PMC7940109 DOI: 10.3934/neuroscience.2021011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 11/22/2020] [Indexed: 12/27/2022] Open
Abstract
Alcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between MTHFR gene C677T (rs1801133) polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the MTHFRC677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR = 1.02, 95% CI = 0.62-1.68; for TT+CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT+CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between MTHFR C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.
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Affiliation(s)
- Vandana Rai
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur-222 003, UP, India
| | - Pradeep Kumar
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur-222 003, UP, India
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29
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Abstract
Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17-93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04-1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.
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30
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Borruto AM, Stopponi S, Li H, Weiss F, Roberto M, Ciccocioppo R. Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation? Neuropharmacology 2021; 186:108446. [PMID: 33476639 DOI: 10.1016/j.neuropharm.2020.108446] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/24/2020] [Accepted: 12/29/2020] [Indexed: 12/15/2022]
Abstract
For several decades, genetically selected alcohol-preferring rats have been successfully used to mimic and study alcohol use disorders (AUD). These rat lines have been instrumental in advancing our understanding of the neurobiology of alcoholism and enabling pharmacological studies to evaluate drug efficacy on alcohol drinking and relapse. Moreover, the results of these studies have identified genetic variables that are linked to AUD vulnerability. This is an up-to-date review that focuses on genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. To support the translational relevance of the findings that are obtained from msP rats and highlight important similarities to AUD patients, we also discuss the results of recent brain imaging studies. Finally, to demonstrate the importance of studying sex differences in animal models of AUD, we present original data that highlight behavioral differences in the response to alcohol in male and female rats. Female msP rats exhibited higher alcohol consumption compared with males. Furthermore, msP rats of both sexes exhibit higher anxiety- and depressive-like behaviors in the elevated plus maze and forced swim test, respectively, compared with unselected Wistar controls. Notably, voluntary alcohol drinking decreases foot-shock stress and depressive-like behavior in both sexes, whereas anxiety-like behavior in the elevated plus maze is attenuated only in males. These findings suggest that male and female msP rats both drink high amounts of alcohol to self-medicate negative affective symptoms. For females, this behavior may be driven by an attempt to treat stress and depressive-like conditions. For males, generalized anxiety appears to be an important additional factor in the motivation to drink alcohol. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'
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Affiliation(s)
- Anna Maria Borruto
- School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy
| | - Serena Stopponi
- School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy
| | - Hongwu Li
- College of Chemical Engineering, Changchun University of Technology, Changchun, China
| | - Friedbert Weiss
- Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA
| | - Marisa Roberto
- Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA
| | - Roberto Ciccocioppo
- School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
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Sanvisens A, Zuluaga P, Short A, Rubio G, Gual A, Torrens M, Fuster D, Bolao F, Rodríguez de Fonseca F, Muga R. Sex-specific Associations of Alcohol Withdrawal in Patients Admitted for the Treatment of Alcohol Use Disorder. J Addict Med 2021; 15:68-73. [PMID: 32769772 DOI: 10.1097/adm.0000000000000704] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES There are sex differences in the pattern of alcohol consumption and in the complications of alcohol use disorder (AUD). We aimed to identify sex-specific differences in the factors associated with alcohol withdrawal syndrome (AWS) among patients that requested a first treatment for AUD. METHODS We enrolled 313 patients (75% men) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis that started treatment between 2014 and 2016. We collected socio-demographics, the type and amount of alcohol and other substances consumed, and clinical and laboratory parameters. According to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD criteria, AWS occurred when patients experienced 2 or more clinical signs/symptoms and/or consumed alcohol to relieve symptoms. Logistic regression models were used to determine factors associated with AWS according to sex. RESULTS The median age of participants was 50 years (interquartile range [IQR]: 43-54 years). The median age of starting alcohol consumption was 16 years (IQR: 14-18 years). Notably, 69% of participants smoked tobacco, and 61% had a family history of AUD; 18% currently used cannabis, and 7.7% used cocaine. Overall, 73% of patients exhibited AWS criteria, and men (76.5%) were more likely than women (64.6%) to report AWS (P = 0.038). In the adjusted analysis, factors associated with AWS were the age at starting alcohol consumption (odds ratio [OR] for every 5 years = 1.89, 95% confidence interval [CI]: 1.69-2.08), and cannabis use (OR = 2.8, 95% CI: 1.04-7.7) in men, and a family history of AUD in women (OR = 2.85 95% CI: 1.07-7.54). CONCLUSIONS factors associated with AWS differ by sex which may have clinical implications for proactive management of AWS during treatment for AUD.
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Affiliation(s)
- Arantza Sanvisens
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol - IGTP, Universitat Autònoma de Barcelona, Spain (AS, PZ, DF, RM); Alcohol Unit, Hospital Universitari Son Espases - IdISPa, Palma de Mallorca, Spain (AS); Department of Psychiatry, Hospital Universitario 12 de Octubre - Instituto i+12, Universidad Complutense de Madrid, Spain (GR); Department of Psychiatry, Hospital Clínic de Barcelona - IDIBAPS, Universitat de Barcelona, Spain (AG); Department of Neuropsychiatry and Addictions, Hospital del Mar - IMIM, Universitat Autònoma de Barcelona, Spain (MT); Department of Internal Medicine, Hospital Universitari de Bellvitge- IDIBELL, L'Hospitalet de Llobregat, Spain (FB); IBIMA Biomedical Research Institut - Málaga, Spain (FRdF)
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32
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Bender AK, Meyers JL, di Viteri SSS, Schuckit M, Chan G, Acion L, Kamarajan C, Kramer J, Anohkin A, Kinreich S, Pandey A, Hesselbrock V, Hesselbrock M, Bucholz KK, McCutcheon VV. A latent class analysis of alcohol and posttraumatic stress symptoms among offspring of parents with and without alcohol use disorder. Addict Behav 2021; 112:106640. [PMID: 32957005 PMCID: PMC10913466 DOI: 10.1016/j.addbeh.2020.106640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 08/28/2020] [Accepted: 08/30/2020] [Indexed: 11/27/2022]
Abstract
The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is widely known, yet few studies have examined whether and how AUD symptoms co-occur with PTSD symptom clusters of hypervigilance, avoidance/numbing, and re-experiencing. The purpose of this study was to examine potential overlap between AUD and posttraumatic stress symptomatology, and to characterize the resultant latent classes in terms of demographics, drinking behaviors, parental AUD, and specific traumas experienced (physical violence, sexual violence, and non-assaultive trauma). We hypothesized that classes would be differentiated by type and severity of AUD and PTS symptoms. Drawing from a sample of white and Black participants from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined young adults between the ages of 18-35 who had experienced trauma (N = 2478). A series of LCA models based on the type of trauma experienced, posttraumatic stress symptoms and problematic alcohol use were then fitted to the data. A four-class solution provided the best fit, consisting of a low symptom class (N = 1134), moderate alcohol/low PTS severity (N = 623), mild alcohol/high PTS severity (N = 544), and high symptom severity (N = 177). Higher prevalence of sexual assault was associated with membership in high PTS severity classes, and parent AUD was associated with membership in each class, particularly when the mother or both parents had the disorder. Using person-centered methods such as LCA is a commonsense approach to understanding the heterogeneity of symptoms, trauma types, and individual-level characteristics associated with trauma-exposed individuals and comorbid AUD-PTSD, and our study is one of relatively few to empirically ascertain the co-occurrence of alcohol and PTS symptoms in a high-risk family sample.
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Affiliation(s)
| | | | | | | | - Grace Chan
- University of Connecticut, United States
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33
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Munn‐Chernoff MA, Johnson EC, Chou Y, Coleman JR, Thornton LM, Walters RK, Yilmaz Z, Baker JH, Hübel C, Gordon S, Medland SE, Watson HJ, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Ripke S, Yao S, Giusti‐Rodríguez P, Hanscombe KB, Adan RA, Alfredsson L, Ando T, Andreassen OA, Berrettini WH, Boehm I, Boni C, Boraska Perica V, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OS, Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak‐Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández‐Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Gratacos Mayora M, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz‐Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez‐Murcia S, Julià A, Kalsi G, Kaminská D, Karhunen L, Karwautz A, Kas MJ, Kennedy JL, Keski‐Rahkonen A, Kiezebrink K, Kim Y, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Nacmias B, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn‐Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof‐Op't Landt MC, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz‐Nwafor M, Tziouvas K, Elburg AA, Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell J, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Grove J, Henders AK, Larsen JT, Parker R, Petersen LV, Jordan J, Kennedy MA, Birgegård A, Lichtenstein P, Norring C, Landén M, Mortensen PB, Polimanti R, McClintick JN, Adkins AE, Aliev F, Bacanu S, Batzler A, Bertelsen S, Biernacka JM, Bigdeli TB, Chen L, Clarke T, Degenhardt F, Docherty AR, Edwards AC, Foo JC, Fox L, Frank J, Hack LM, Hartmann AM, Hartz SM, Heilmann‐Heimbach S, Hodgkinson C, Hoffmann P, Hottenga J, Konte B, Lahti J, Lahti‐Pulkkinen M, Lai D, Ligthart L, Loukola A, Maher BS, Mbarek H, McIntosh AM, McQueen MB, Meyers JL, Milaneschi Y, Palviainen T, Peterson RE, Ryu E, Saccone NL, Salvatore JE, Sanchez‐Roige S, Schwandt M, Sherva R, Streit F, Strohmaier J, Thomas N, Wang J, Webb BT, Wedow R, Wetherill L, Wills AG, Zhou H, Boardman JD, Chen D, Choi D, Copeland WE, Culverhouse RC, Dahmen N, Degenhardt L, Domingue BW, Frye MA, Gäebel W, Hayward C, Ising M, Keyes M, Kiefer F, Koller G, Kramer J, Kuperman S, Lucae S, Lynskey MT, Maier W, Mann K, Männistö S, Müller‐Myhsok B, Murray AD, Nurnberger JI, Preuss U, Räikkönen K, Reynolds MD, Ridinger M, Scherbaum N, Schuckit MA, Soyka M, Treutlein J, Witt SH, Wodarz N, Zill P, Adkins DE, Boomsma DI, Bierut LJ, Brown SA, Bucholz KK, Costello EJ, Wit H, Diazgranados N, Eriksson JG, Farrer LA, Foroud TM, Gillespie NA, Goate AM, Goldman D, Grucza RA, Hancock DB, Harris KM, Hesselbrock V, Hewitt JK, Hopfer CJ, Iacono WG, Johnson EO, Karpyak VM, Kendler KS, Kranzler HR, Krauter K, Lind PA, McGue M, MacKillop J, Madden PA, Maes HH, Magnusson PK, Nelson EC, Nöthen MM, Palmer AA, Penninx BW, Porjesz B, Rice JP, Rietschel M, Riley BP, Rose RJ, Shen P, Silberg J, Stallings MC, Tarter RE, Vanyukov MM, Vrieze S, Wall TL, Whitfield JB, Zhao H, Neale BM, Wade TD, Heath AC, Montgomery GW, Martin NG, Sullivan PF, Kaprio J, Breen G, Gelernter J, Edenberg HJ, Bulik CM, Agrawal A. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies. Addict Biol 2021; 26:e12880. [DOI: 10.1111/adb.12880] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/09/2019] [Accepted: 01/13/2020] [Indexed: 02/01/2023]
Affiliation(s)
- Melissa A. Munn‐Chernoff
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Emma C. Johnson
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Yi‐Ling Chou
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Jonathan R.I. Coleman
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
- National Institute for Health Research Biomedical Research Centre King's College London and South London and Maudsley National Health Service Trust London UK
| | - Laura M. Thornton
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Raymond K. Walters
- Analytic and Translational Genetics Unit, Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA
- Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts USA
| | - Zeynep Yilmaz
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Jessica H. Baker
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Christopher Hübel
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
- National Institute for Health Research Biomedical Research Centre King's College London and South London and Maudsley National Health Service Trust London UK
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Scott Gordon
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Sarah E. Medland
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Hunna J. Watson
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- School of Psychology Curtin University Perth Western Australia Australia
- School of Paediatrics and Child Health University of Western Australia Perth Western Australia Australia
| | - Héléna A. Gaspar
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
- National Institute for Health Research Biomedical Research Centre King's College London and South London and Maudsley National Health Service Trust London UK
| | - Julien Bryois
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Anke Hinney
- Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg‐Essen Essen Germany
| | - Virpi M. Leppä
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Manuel Mattheisen
- Department of Biomedicine Aarhus University Aarhus Denmark
- Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
- Center for Psychiatry Research, Stockholm Health Care Services Stockholm County Council Stockholm Sweden
- Department of Psychiatry, Psychosomatics and Psychotherapy University of Würzburg Germany
| | - Stephan Ripke
- Analytic and Translational Genetics Unit, Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA
- Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts USA
- Department of Psychiatry and Psychotherapy Charité ‐ Universitätsmedizin Berlin Germany
| | - Shuyang Yao
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Paola Giusti‐Rodríguez
- Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Ken B. Hanscombe
- Department of Medical and Molecular Genetics King's College London, Guy's Hospital London UK
| | - Roger A.H. Adan
- Department of Translational Neuroscience, Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
- Center for Eating Disorders Rintveld Altrecht Mental Health Institute Zeist The Netherlands
- Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
| | - Lars Alfredsson
- Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
| | - Tetsuya Ando
- Department of Behavioral Medicine, National Institute of Mental Health National Center of Neurology and Psychiatry Kodaira Tokyo Japan
| | - Ole A. Andreassen
- NORMENT Centre, Division of Mental Health and Addiction, NORMENT Centre University of Oslo, Oslo University Hospital Oslo Norway
| | - Wade H. Berrettini
- Department of Psychiatry, Center for Neurobiology and Behavior University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA
| | - Ilka Boehm
- Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine Technische Universität Dresden Dresden Germany
| | - Claudette Boni
- Centre of Psychiatry and Neuroscience INSERM U894 Paris France
| | - Vesna Boraska Perica
- Wellcome Sanger Institute, Wellcome Genome Campus Hinxton Cambridge UK
- Department of Medical Biology, School of Medicine University of Split Split Croatia
| | - Katharina Buehren
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy RWTH Aachen University Aachen Germany
| | | | - Matteo Cassina
- Clinical Genetics Unit, Department of Woman and Child Health University of Padova Italy
| | - Sven Cichon
- Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
- Department of Biomedicine University of Basel Basel Switzerland
- Institute of Neuroscience and Medicine (INM‐1) Research Center Juelich Germany
| | - Maurizio Clementi
- Clinical Genetics Unit, Department of Woman and Child Health University of Padova Italy
| | - Roger D. Cone
- Department of Molecular and Integrative Physiology, Life Sciences Institute University of Michigan Ann Arbor Michigan USA
| | - Philippe Courtet
- Department of Emergency Psychiatry and Post‐Acute Care, CHRU Montpellier University of Montpellier Montpellier France
| | - Scott Crow
- Department of Psychiatry University of Minnesota Minneapolis Minnesota USA
| | - James J. Crowley
- Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
| | - Unna N. Danner
- Altrecht Eating Disorders Rintveld Altrecht Mental Health Institute Zeist The Netherlands
| | - Oliver S.P. Davis
- MRC Integrative Epidemiology Unit University of Bristol Bristol UK
- School of Social and Community Medicine University of Bristol Bristol UK
| | - Martina Zwaan
- Department of Psychosomatic Medicine and Psychotherapy Hannover Medical School Hannover Germany
| | - George Dedoussis
- Department of Nutrition and Dietetics Harokopio University Athens Greece
| | | | | | - Danielle M. Dick
- Department of Psychology Virginia Commonwealth University Richmond Virginia USA
- College Behavioral and Emotional Health Institute Virginia Commonwealth University Richmond Virginia USA
- Department of Human & Molecular Genetics Virginia Commonwealth University Richmond Virginia USA
| | - Dimitris Dikeos
- Department of Psychiatry, Athens University Medical School Athens University Athens Greece
| | - Christian Dina
- l'institut du thorax INSERM, CNRS, Univ Nantes Nantes France
| | | | - Elisa Docampo
- Barcelona Institute of Science and Technology Barcelona Spain
- Universitat Pompeu Fabra Barcelona Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP) Barcelona Spain
| | - Laramie E. Duncan
- Department of Psychiatry and Behavioral Sciences Stanford University Stanford California USA
| | - Karin Egberts
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health University Hospital of Würzburg Würzburg Germany
| | - Stefan Ehrlich
- Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine Technische Universität Dresden Dresden Germany
| | - Geòrgia Escaramís
- Barcelona Institute of Science and Technology Barcelona Spain
- Universitat Pompeu Fabra Barcelona Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP) Barcelona Spain
| | - Tõnu Esko
- Estonian Genome Center University of Tartu Tartu Estonia
- Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge Massachusetts USA
| | - Xavier Estivill
- Barcelona Institute of Science and Technology Barcelona Spain
- Universitat Pompeu Fabra Barcelona Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP) Barcelona Spain
- Genomics and Disease, Bioinformatics and Genomics Programme Centre for Genomic Regulation Barcelona Spain
| | - Anne Farmer
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | - Angela Favaro
- Department of Neurosciences University of Padova Padova Italy
| | - Fernando Fernández‐Aranda
- Department of Psychiatry University Hospital of Bellvitge –IDIBELL and CIBERobn Barcelona Spain
- Department of Clinical Sciences, School of Medicine University of Barcelona Barcelona Spain
| | - Manfred M. Fichter
- Department of Psychiatry and Psychotherapy Ludwig‐Maximilians‐University Munich Germany
- Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich Munich Germany
| | - Krista Fischer
- Estonian Genome Center University of Tartu Tartu Estonia
| | - Manuel Föcker
- Department of Child and Adolescent Psychiatry University of Münster Münster Germany
| | - Lenka Foretova
- Department of Cancer, Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
| | - Andreas J. Forstner
- Department of Biomedicine University of Basel Basel Switzerland
- Centre for Human Genetics University of Marburg Marburg Germany
- Institute of Human Genetics School of Medicine & University Hospital Bonn, University of Bonn Bonn Germany
- Department of Psychiatry (UPK) University of Basel Basel Switzerland
| | - Monica Forzan
- Clinical Genetics Unit, Department of Woman and Child Health University of Padova Italy
| | | | - Steven Gallinger
- Department of Surgery, Faculty of Medicine University of Toronto Toronto Ontario Canada
| | - Ina Giegling
- Department of Psychiatry, Psychotherapy and Psychosomatics Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) Germany
| | - Johanna Giuranna
- Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg‐Essen Essen Germany
| | - Fragiskos Gonidakis
- 1st Psychiatric Department National and Kapodistrian University of Athens, Medical School, Eginition Hospital Athens Greece
| | - Philip Gorwood
- Institute of Psychiatry and Neuroscience of Paris INSERM U1266 Paris France
- CMME (GHU Paris Psychiatrie et Neurosciences), Paris Descartes University Paris France
| | - Monica Gratacos Mayora
- Barcelona Institute of Science and Technology Barcelona Spain
- Universitat Pompeu Fabra Barcelona Spain
- Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP) Barcelona Spain
| | - Sébastien Guillaume
- Department of Emergency Psychiatry and Post‐Acute Care, CHRU Montpellier University of Montpellier Montpellier France
| | - Yiran Guo
- Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA
| | - Hakon Hakonarson
- Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA
- Department of Pediatrics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA
| | - Konstantinos Hatzikotoulas
- Wellcome Sanger Institute, Wellcome Genome Campus Hinxton Cambridge UK
- Institute of Translational Genomics, Helmholtz Zentrum München ‐ German Research Centre for Environmental Health Neuherberg Germany
| | - Joanna Hauser
- Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland
| | - Johannes Hebebrand
- Department of Child and Adolescent Psychiatry University Hospital Essen, University of Duisburg‐Essen Essen Germany
| | - Sietske G. Helder
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
- Zorg op Orde Delft The Netherlands
| | - Stefan Herms
- Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
- Department of Biomedicine University of Basel Basel Switzerland
| | - Beate Herpertz‐Dahlmann
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy RWTH Aachen University Aachen Germany
| | - Wolfgang Herzog
- Department of General Internal Medicine and Psychosomatics Heidelberg University Hospital, Heidelberg University Heidelberg Germany
| | - Laura M. Huckins
- Wellcome Sanger Institute, Wellcome Genome Campus Hinxton Cambridge UK
- Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics Icahn School of Medicine at Mount Sinai New York New York USA
| | - James I. Hudson
- Biological Psychiatry Laboratory McLean Hospital/Harvard Medical School Boston Massachusetts USA
| | - Hartmut Imgart
- Eating Disorders Unit Parklandklinik Bad Wildungen Germany
| | - Hidetoshi Inoko
- Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine Tokai University Isehara Japan
| | - Vladimir Janout
- Faculty of Health Sciences Palacky University Olomouc Czech Republic
| | - Susana Jiménez‐Murcia
- Department of Psychiatry University Hospital of Bellvitge –IDIBELL and CIBERobn Barcelona Spain
- Department of Clinical Sciences, School of Medicine University of Barcelona Barcelona Spain
| | - Antonio Julià
- Rheumatology Research Group Vall d'Hebron Research Institute Barcelona Spain
| | - Gursharan Kalsi
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | - Deborah Kaminská
- Department of Psychiatry, First Faculty of Medicine Charles University Prague Czech Republic
| | - Leila Karhunen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition University of Eastern Finland Kuopio Finland
| | - Andreas Karwautz
- Eating Disorders Unit, Department of Child and Adolescent Psychiatry Medical University of Vienna Vienna Austria
| | - Martien J.H. Kas
- Department of Translational Neuroscience, Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
- Groningen Institute for Evolutionary Life Sciences University of Groningen Groningen The Netherlands
| | - James L. Kennedy
- Centre for Addiction and Mental Health Toronto Ontario Canada
- Institute of Medical Science University of Toronto Toronto Ontario Canada
- Department of Psychiatry University of Toronto Toronto Ontario Canada
| | | | - Kirsty Kiezebrink
- Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition University of Aberdeen Aberdeen UK
| | - Youl‐Ri Kim
- Department of Psychiatry Seoul Paik Hospital, Inje University Seoul Korea
| | - Kelly L. Klump
- Department of Psychology Michigan State University East Lansing Michigan USA
| | | | - Maria C. La Via
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Stephanie Le Hellard
- Department of Clinical Science, Norwegian Centre for Mental Disorders Research (NORMENT) University of Bergen Bergen Norway
- Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway
- Department of Clinical Medicine, Laboratory Building Haukeland University Hospital Bergen Norway
| | - Robert D. Levitan
- Centre for Addiction and Mental Health Toronto Ontario Canada
- Institute of Medical Science University of Toronto Toronto Ontario Canada
- Department of Psychiatry University of Toronto Toronto Ontario Canada
| | - Dong Li
- Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA
| | - Lisa Lilenfeld
- The Chicago School of Professional Psychology, Washington DC Campus Washington District of Columbia USA
| | - Bochao Danae Lin
- Department of Translational Neuroscience, Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
| | - Jolanta Lissowska
- Department of Cancer Epidemiology and Prevention M Skłodowska‐Curie Cancer Center ‐ Oncology Center Warsaw Poland
| | - Jurjen Luykx
- Department of Translational Neuroscience, Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht The Netherlands
| | - Pierre J. Magistretti
- BESE Division King Abdullah University of Science and Technology Thuwal Saudi Arabia
- Department of Psychiatry University of Lausanne‐University Hospital of Lausanne (UNIL‐CHUV) Lausanne Switzerland
| | - Mario Maj
- Department of Psychiatry University of Campania "Luigi Vanvitelli" Naples Italy
| | - Katrin Mannik
- Estonian Genome Center University of Tartu Tartu Estonia
- Center for Integrative Genomics University of Lausanne Lausanne Switzerland
| | - Sara Marsal
- Rheumatology Research Group Vall d'Hebron Research Institute Barcelona Spain
| | - Christian R. Marshall
- Department of Paediatric Laboratory Medicine, Division of Genome Diagnostics The Hospital for Sick Children Toronto Ontario Canada
| | - Morten Mattingsdal
- NORMENT KG Jebsen Centre, Division of Mental Health and Addiction University of Oslo, Oslo University Hospital Oslo Norway
| | - Sara McDevitt
- Department of Psychiatry University College Cork Cork Ireland
- Eist Linn Adolescent Unit, Bessborough Health Service Executive South Cork Ireland
| | - Peter McGuffin
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | - Andres Metspalu
- Estonian Genome Center University of Tartu Tartu Estonia
- Institute of Molecular and Cell Biology University of Tartu Tartu Estonia
| | - Ingrid Meulenbelt
- Molecular Epidemiology Section (Department of Biomedical Datasciences) Leiden University Medical Centre Leiden The Netherlands
| | - Nadia Micali
- Department of Psychiatry, Faculty of Medicine University of Geneva Geneva Switzerland
- Division of Child and Adolescent Psychiatry Geneva University Hospital Geneva Switzerland
| | - Karen Mitchell
- National Center for PTSD VA Boston Healthcare System Boston Massachusetts USA
- Department of Psychiatry Boston University School of Medicine Boston Massachusetts USA
| | | | - Palmiero Monteleone
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" University of Salerno Salerno Italy
| | - Benedetta Nacmias
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA) University of Florence Florence Italy
| | - Marie Navratilova
- Department of Cancer, Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
| | - Ioanna Ntalla
- Department of Nutrition and Dietetics Harokopio University Athens Greece
| | | | - Roel A. Ophoff
- Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior University of California Los Angeles Los Angeles California USA
- Department of Psychiatry, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
| | - Leonid Padyukov
- Department of Medicine, Center for Molecular Medicine, Division of Rheumatology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
| | - Aarno Palotie
- Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge Massachusetts USA
- Institute for Molecular Medicine FIMM, HiLIFE University of Helsinki Helsinki Finland
- Center for Human Genome Research Massachusetts General Hospital Boston Massachusetts USA
| | - Jacques Pantel
- Centre of Psychiatry and Neuroscience INSERM U894 Paris France
| | - Hana Papezova
- Department of Psychiatry, First Faculty of Medicine Charles University Prague Czech Republic
| | - Dalila Pinto
- Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics Icahn School of Medicine at Mount Sinai New York New York USA
| | - Raquel Rabionet
- Saint Joan de Déu Research Institute Saint Joan de Déu Barcelona Children's Hospital Barcelona Spain
- Institute of Biomedicine (IBUB) University of Barcelona Barcelona Spain
- Department of Genetics, Microbiology and Statistics University of Barcelona Barcelona Spain
| | - Anu Raevuori
- Department of Public Health University of Helsinki Helsinki Finland
| | - Nicolas Ramoz
- Institute of Psychiatry and Neuroscience of Paris INSERM U1266 Paris France
| | - Ted Reichborn‐Kjennerud
- Department of Mental Disorders Norwegian Institute of Public Health Oslo Norway
- Institute of Clinical Medicine University of Oslo Oslo Norway
| | - Valdo Ricca
- Department of Health Science University of Florence Florence Italy
| | - Samuli Ripatti
- Department of Biometry University of Helsinki Helsinki Finland
| | - Franziska Ritschel
- Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine Technische Universität Dresden Dresden Germany
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Eating Disorders Research and Treatment Center Technische Universität Dresden Dresden Germany
| | - Marion Roberts
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | - Alessandro Rotondo
- Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies University of Pisa Pisa Italy
| | - Dan Rujescu
- Department of Psychiatry, Psychotherapy and Psychosomatics Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) Germany
| | - Filip Rybakowski
- Department of Psychiatry Poznan University of Medical Sciences Poznan Poland
| | - Paolo Santonastaso
- Department of Neurosciences, Padua Neuroscience Center University of Padova Padova Italy
| | - André Scherag
- Institute of Medical Statistics, Computer and Data Sciences Jena University Hospital Jena Germany
| | - Stephen W. Scherer
- Department of Genetics and Genomic Biology The Hospital for Sick Children Toronto Ontario Canada
- McLaughlin Centre University of Toronto Toronto Ontario Canada
| | - Ulrike Schmidt
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | | | - Alexandra Schosser
- Department of Psychiatry and Psychotherapy Medical University of Vienna Vienna Austria
| | - Jochen Seitz
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy RWTH Aachen University Aachen Germany
| | - Lenka Slachtova
- Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine Charles University Prague Czech Republic
| | - P. Eline Slagboom
- Molecular Epidemiology Section (Department of Medical Statistics) Leiden University Medical Centre Leiden The Netherlands
| | - Margarita C.T. Slof‐Op't Landt
- Center for Eating Disorders Ursula Rivierduinen Leiden The Netherlands
- Department of Psychiatry Leiden University Medical Centre Leiden The Netherlands
| | - Agnieszka Slopien
- Department of Child and Adolescent Psychiatry Poznan University of Medical Sciences Poznan Poland
| | - Sandro Sorbi
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA) University of Florence Florence Italy
- IRCCS Fondazione Don Carlo Gnocchi Florence Italy
| | - Beata Świątkowska
- Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lodz Poland
| | - Jin P. Szatkiewicz
- Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | | | - Elena Tenconi
- Department of Neurosciences University of Padova Padova Italy
| | - Alfonso Tortorella
- Department of Psychiatry University of Naples SUN Naples Italy
- Department of Psychiatry University of Perugia Perugia Italy
| | - Federica Tozzi
- Brain Sciences Department Stremble Ventures Limassol Cyprus
| | - Janet Treasure
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
| | - Artemis Tsitsika
- Adolescent Health Unit, Second Department of Pediatrics "P. & A. Kyriakou" Children's Hospital, University of Athens Athens Greece
| | - Marta Tyszkiewicz‐Nwafor
- Department of Child and Adolescent Psychiatry Poznan University of Medical Sciences Poznan Poland
| | - Konstantinos Tziouvas
- Pediatric Intensive Care Unit "P. & A. Kyriakou" Children's Hospital, University of Athens Athens Greece
| | - Annemarie A. Elburg
- Center for Eating Disorders Rintveld Altrecht Mental Health Institute Zeist The Netherlands
- Faculty of Social and Behavioral Sciences Utrecht University Utrecht The Netherlands
| | - Eric F. Furth
- Center for Eating Disorders Ursula Rivierduinen Leiden The Netherlands
- Department of Psychiatry Leiden University Medical Centre Leiden The Netherlands
| | - Gudrun Wagner
- Eating Disorders Unit, Department of Child and Adolescent Psychiatry Medical University of Vienna Vienna Austria
| | - Esther Walton
- Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine Technische Universität Dresden Dresden Germany
| | - Elisabeth Widen
- Institute for Molecular Medicine FIMM, HiLIFE University of Helsinki Helsinki Finland
| | - Eleftheria Zeggini
- Wellcome Sanger Institute, Wellcome Genome Campus Hinxton Cambridge UK
- Institute of Translational Genomics, Helmholtz Zentrum München ‐ German Research Centre for Environmental Health Neuherberg Germany
| | - Stephanie Zerwas
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Stephan Zipfel
- Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy University Medical Hospital Tuebingen Tuebingen Germany
| | - Andrew W. Bergen
- BioRealm, LLC Walnut California USA
- Oregon Research Institute Eugene Oregon USA
| | - Joseph M. Boden
- Christchurch Health and Development Study University of Otago Christchurch New Zealand
| | - Harry Brandt
- The Center for Eating Disorders at Sheppard Pratt Baltimore Maryland USA
| | - Steven Crawford
- The Center for Eating Disorders at Sheppard Pratt Baltimore Maryland USA
| | - Katherine A. Halmi
- Department of Psychiatry Weill Cornell Medical College New York New York USA
| | - L. John Horwood
- Christchurch Health and Development Study University of Otago Christchurch New Zealand
| | | | - Allan S. Kaplan
- Centre for Addiction and Mental Health Toronto Ontario Canada
- Institute of Medical Science University of Toronto Toronto Ontario Canada
- Department of Psychiatry University of Toronto Toronto Ontario Canada
| | - Walter H. Kaye
- Department of Psychiatry University of California San Diego La Jolla California USA
| | - James Mitchell
- Department of Psychiatry and Behavioral Science University of North Dakota School of Medicine and Health Sciences Fargo North Dakota USA
| | - Catherine M. Olsen
- Population Health Department QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - John F. Pearson
- Biostatistics and Computational Biology Unit University of Otago Christchurch New Zealand
| | - Nancy L. Pedersen
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Michael Strober
- Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior University of California Los Angeles Los Angeles California USA
- David Geffen School of Medicine University of California Los Angeles Los Angeles California USA
| | - Thomas Werge
- Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
| | - David C. Whiteman
- Population Health Department QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - D. Blake Woodside
- Institute of Medical Science University of Toronto Toronto Ontario Canada
- Department of Psychiatry University of Toronto Toronto Ontario Canada
- Centre for Mental Health University Health Network Toronto Ontario Canada
- Program for Eating Disorders University Health Network Toronto Ontario Canada
| | - Jakob Grove
- Department of Biomedicine Aarhus University Aarhus Denmark
- The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) Aarhus Denmark
- Centre for Integrative Sequencing, iSEQ Aarhus University Aarhus Denmark
- Bioinformatics Research Centre Aarhus University Aarhus Denmark
| | - Anjali K. Henders
- Institute for Molecular Bioscience University of Queensland Brisbane Queensland Australia
| | - Janne T. Larsen
- The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) Aarhus Denmark
- National Centre for Register‐Based Research, Aarhus BSS Aarhus University Aarhus Denmark
- Centre for Integrated Register‐based Research (CIRRAU) Aarhus University Aarhus Denmark
| | - Richard Parker
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Liselotte V. Petersen
- The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) Aarhus Denmark
- National Centre for Register‐Based Research, Aarhus BSS Aarhus University Aarhus Denmark
- Centre for Integrated Register‐based Research (CIRRAU) Aarhus University Aarhus Denmark
| | - Jennifer Jordan
- Department of Psychological Medicine University of Otago Christchurch New Zealand
- Canterbury District Health Board Christchurch New Zealand
| | - Martin A. Kennedy
- Department of Pathology and Biomedical Science University of Otago Christchurch New Zealand
| | - Andreas Birgegård
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
- Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
- Center for Psychiatry Research, Stockholm Health Care Services Stockholm County Council Stockholm Sweden
| | - Paul Lichtenstein
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Claes Norring
- Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
- Center for Psychiatry Research, Stockholm Health Care Services Stockholm County Council Stockholm Sweden
| | - Mikael Landén
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden
| | - Preben Bo Mortensen
- The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) Aarhus Denmark
- National Centre for Register‐Based Research, Aarhus BSS Aarhus University Aarhus Denmark
- Centre for Integrated Register‐based Research (CIRRAU) Aarhus University Aarhus Denmark
| | - Renato Polimanti
- Department of Psychiatry, Division of Human Genetics Yale School of Medicine New Haven Connecticut USA
- Veterans Affairs Connecticut Healthcare System West Haven Connecticut USA
| | - Jeanette N. McClintick
- Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis Indiana USA
| | - Amy E. Adkins
- Department of Psychology Virginia Commonwealth University Richmond Virginia USA
- College Behavioral and Emotional Health Institute Virginia Commonwealth University Richmond Virginia USA
| | - Fazil Aliev
- Department of Psychology Virginia Commonwealth University Richmond Virginia USA
- Faculty of Business Karabuk University Karabuk Turkey
| | - Silviu‐Alin Bacanu
- Virginia Commonwealth University Alcohol Research Center Virginia Commonwealth University Richmond Virginia USA
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Anthony Batzler
- Psychiatric Genomics and Pharmacogenomics Program Mayo Clinic Rochester Minnesota USA
| | - Sarah Bertelsen
- Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York USA
| | - Joanna M. Biernacka
- Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA
- Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA
| | - Tim B. Bigdeli
- Department of Psychiatry and Behavioral Sciences State University of New York Downstate Medical Center Brooklyn New York USA
| | - Li‐Shiun Chen
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | | | - Franziska Degenhardt
- Institute of Human Genetics University of Bonn School of Medicine & University Hospital Bonn Bonn Germany
| | - Anna R. Docherty
- Department of Psychiatry University of Utah Salt Lake City Utah USA
| | - Alexis C. Edwards
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Jerome C. Foo
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Louis Fox
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Josef Frank
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Laura M. Hack
- Department of Psychiatry and Behavioral Sciences Stanford University Stanford California USA
| | - Annette M. Hartmann
- Department of Psychiatry, Psychotherapy and Psychosomatics Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) Germany
| | - Sarah M. Hartz
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Stefanie Heilmann‐Heimbach
- Institute of Human Genetics University of Bonn School of Medicine & University Hospital Bonn Bonn Germany
| | | | - Per Hoffmann
- Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
- Institute of Human Genetics School of Medicine & University Hospital Bonn, University of Bonn Bonn Germany
- Human Genomics Research Group, Department of Biomedicine University of Basel Basel Switzerland
| | - Jouke‐Jan Hottenga
- Department of Biological Psychology, Amsterdam Public Health Research Institute Vrije Universiteit Amsterdam Amsterdam The Netherlands
| | - Bettina Konte
- Department of Psychiatry, Psychotherapy and Psychosomatics Martin‐Luther‐University Halle‐Wittenberg Halle (Saale) Germany
| | - Jari Lahti
- Turku Institute for Advanced Studies University of Turku Turku Finland
| | | | - Dongbing Lai
- Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA
| | - Lannie Ligthart
- Department of Biological Psychology, Amsterdam Public Health Research Institute Vrije Universiteit Amsterdam Amsterdam The Netherlands
| | - Anu Loukola
- Institute for Molecular Medicine FIMM, HiLIFE University of Helsinki Helsinki Finland
| | - Brion S. Maher
- Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA
| | - Hamdi Mbarek
- Department of Biological Psychology, Amsterdam Public Health Research Institute Vrije Universiteit Amsterdam Amsterdam The Netherlands
| | - Andrew M. McIntosh
- Division of Psychiatry, Centre for Cognitive Ageing and Cognitive Epidemiology University of Edinburgh Edinburgh UK
| | - Matthew B. McQueen
- Department of Integrative Physiology University of Colorado Boulder Boulder Colorado USA
| | - Jacquelyn L. Meyers
- Department of Psychiatry and Behavioral Sciences, Henri Begleiter Neurodynamics Laboratory SUNY Downstate Medical Center Brooklyn New York USA
| | - Yuri Milaneschi
- Department of Psychiatry, Amsterdam Public Health Research Institute VU University Medical Center/GGz inGeest Amsterdam The Netherlands
| | - Teemu Palviainen
- Institute for Molecular Medicine FIMM, HiLIFE University of Helsinki Helsinki Finland
| | - Roseann E. Peterson
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Euijung Ryu
- Department of Health Sciences Research Mayo Clinic Rochester Minnesota USA
| | - Nancy L. Saccone
- Department of Genetics Washington University School of Medicine Saint Louis Missouri USA
| | - Jessica E. Salvatore
- Department of Psychology Virginia Commonwealth University Richmond Virginia USA
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Sandra Sanchez‐Roige
- Department of Psychiatry University of California San Diego La Jolla California USA
| | | | - Richard Sherva
- Department of Medicine (Biomedical Genetics) Boston University School of Medicine Boston Massachusetts USA
| | - Fabian Streit
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Jana Strohmaier
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Nathaniel Thomas
- Department of Psychology Virginia Commonwealth University Richmond Virginia USA
- College Behavioral and Emotional Health Institute Virginia Commonwealth University Richmond Virginia USA
| | - Jen‐Chyong Wang
- Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York USA
| | - Bradley T. Webb
- Virginia Commonwealth University Alcohol Research Center Virginia Commonwealth University Richmond Virginia USA
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Robbee Wedow
- Analytic and Translational Genetics Unit, Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA
- Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health Harvard University Cambridge Massachusetts USA
- Department of Sociology Harvard University Cambridge Massachusetts USA
| | - Leah Wetherill
- Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA
| | - Amanda G. Wills
- Department of Pharmacology University of Colorado School of Medicine Aurora Colorado USA
| | - Hang Zhou
- Department of Psychiatry, Division of Human Genetics Yale School of Medicine New Haven Connecticut USA
- Veterans Affairs Connecticut Healthcare System West Haven Connecticut USA
| | - Jason D. Boardman
- Institute of Behavioral Science University of Colorado Boulder Colorado USA
- Department of Sociology University of Colorado Boulder Colorado USA
| | - Danfeng Chen
- Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts USA
| | - Doo‐Sup Choi
- Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester Minnesota USA
| | - William E. Copeland
- Department of Psychiatry University of Vermont Medical Center Burlington Vermont USA
| | - Robert C. Culverhouse
- Department of Medicine, Division of Biostatistics Washington University School of Medicine Saint Louis Missouri USA
| | - Norbert Dahmen
- Department of Psychiatry University of Mainz Mainz Germany
| | - Louisa Degenhardt
- National Drug and Alcohol Research Centre University of New South Wales Sydney New South Wales Australia
| | - Benjamin W. Domingue
- Stanford University Graduate School of Education Stanford University Stanford California USA
| | - Mark A. Frye
- Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA
| | - Wolfgang Gäebel
- Department of Psychiatry and Psychotherapy University of Düsseldorf Duesseldorf Germany
| | - Caroline Hayward
- MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK
| | - Marcus Ising
- Max‐Planck‐Institute of Psychiatry Munich Germany
| | - Margaret Keyes
- Department of Psychology University of Minnesota Minneapolis Minnesota USA
| | - Falk Kiefer
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Gabriele Koller
- Department of Psychiatry and Psychotherapy University Hospital, LMU Munich Munich Germany
| | - John Kramer
- Department of Psychiatry University of Iowa Roy J and Lucille A Carver College of Medicine Iowa City Iowa USA
| | - Samuel Kuperman
- Department of Psychiatry University of Iowa Roy J and Lucille A Carver College of Medicine Iowa City Iowa USA
| | | | - Michael T. Lynskey
- Addictions Department, Institute of Psychiatry, Psychology & Neuroscience King's College London London UK
| | - Wolfgang Maier
- Department of Psychiatry University of Bonn Bonn Germany
| | - Karl Mann
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Satu Männistö
- Department of Public Health Solutions National Institute for Health and Welfare Helsinki Finland
| | - Bertram Müller‐Myhsok
- Department of Statistical Genetics Max‐Planck‐Institute of Psychiatry München Germany
| | - Alison D. Murray
- Aberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences & Nutrition University of Aberdeen Foresterhill Aberdeen UK
| | - John I. Nurnberger
- Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA
- Department of Psychiatry Indiana University School of Medicine Indianapolis Indiana USA
| | - Ulrich Preuss
- Department of Psychiatry, Psychotherapy and Psychosomatics Martin‐Luther‐University Halle‐Wittenberg Herborn Germany
- Department of Psychiatry and Psychotherapy Vitos Hospital Herborn Herborn Germany
| | - Katri Räikkönen
- Department of Psychology and Logopedics University of Helsinki Helsinki Finland
| | | | - Monika Ridinger
- Department of Psychiatry and Psychotherapy University of Regensburg Psychiatric Health Care Aargau Regensburg Germany
| | - Norbert Scherbaum
- Department of Psychiatry and Psychotherapy and Department of Addictive Behaviour and Addiction Medicine, Medical Faculty LVR‐Hospital Essen, University of Duisburg‐Essen Essen Germany
| | - Marc A. Schuckit
- Department of Psychiatry University of California San Diego La Jolla California USA
| | - Michael Soyka
- Medical Park Chiemseeblick in Bernau‐Felden Ludwig‐Maximilians‐University Bernau am Chiemsee Germany
- Psychiatric Hospital, Ludwig‐Maximilians‐University Bernau am Chiemsee Germany
| | - Jens Treutlein
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Stephanie H. Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Norbert Wodarz
- Department of Psychiatry and Psychotherapy University of Regensburg Regensburg Germany
| | - Peter Zill
- Department of Psychiatry Psychiatric Hospital, Ludwig‐Maximilians‐University Munich Germany
| | - Daniel E. Adkins
- Department of Psychiatry University of Utah Salt Lake City Utah USA
- Department of Sociology University of Utah Salt Lake City Utah USA
| | - Dorret I. Boomsma
- Department of Biological Psychology, Amsterdam Public Health Research Institute Vrije Universiteit Amsterdam Amsterdam The Netherlands
| | - Laura J. Bierut
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Sandra A. Brown
- Department of Psychiatry University of California San Diego La Jolla California USA
- Department of Psychology University of California San Diego La Jolla California USA
| | - Kathleen K. Bucholz
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - E. Jane Costello
- Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham North Carolina USA
| | - Harriet Wit
- Department of Psychiatry and Behavioral Neuroscience University of Chicago Chicago Illinois USA
| | | | - Johan G. Eriksson
- Department of General Practice and Primary Health Care University of Helsinki Helsinki Finland
- National Institute for Health and Welfare Helsinki Finland
| | - Lindsay A. Farrer
- Department of Medicine (Biomedical Genetics) Boston University School of Medicine Boston Massachusetts USA
- Department of Neurology Boston University School of Medicine Boston Massachusetts USA
- Department of Ophthalmology Boston University School of Medicine Boston Massachusetts USA
- Department of Epidemiology, School of Public Health Boston University Boston Massachusetts USA
- Department of Biostatistics, School of Public Health Boston University Boston Massachusetts USA
| | - Tatiana M. Foroud
- Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA
| | - Nathan A. Gillespie
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
| | - Alison M. Goate
- Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York USA
| | - David Goldman
- Laboratory of Neurogenetics NIH/NIAAA Bethesda Maryland USA
- Office of the Clinical Director NIH/NIAAA Besthesda Maryland USA
| | - Richard A. Grucza
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Dana B. Hancock
- Center for Omics Discovery and Epidemiology, Behavioral Health Research Division RTI International Research Triangle Park North Carolina USA
| | - Kathleen Mullan Harris
- Department of Sociology University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Carolina Population Center University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Victor Hesselbrock
- Department of Psychiatry University of Connecticut School of Medicine Farmington Connecticut USA
| | - John K. Hewitt
- Institute for Behavioral Genetics University of Colorado Boulder Boulder Colorado USA
| | | | - William G. Iacono
- Department of Psychology University of Minnesota Minneapolis Minnesota USA
| | - Eric O. Johnson
- Center for Omics Discovery and Epidemiology, Behavioral Health Research Division RTI International Research Triangle Park North Carolina USA
- Fellow Program RTI International Research Triangle Park North Carolina USA
| | - Victor M. Karpyak
- Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA
| | - Kenneth S. Kendler
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Henry R. Kranzler
- Center for Studies of Addiction University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA
- VISN 4 MIRECC Crescenz VAMC Philadelphia Pennsylvania USA
| | - Kenneth Krauter
- Department of Molecular, Cellular, and Developmental Biology University of Colorado Boulder Boulder Colorado USA
| | - Penelope A. Lind
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Matt McGue
- Department of Psychology University of Minnesota Minneapolis Minnesota USA
| | - James MacKillop
- Peter Boris Centre for Addictions Research McMaster University/St. Joseph's Healthcare Hamilton Hamilton Ontario Canada
- Michael G. DeGroote Centre for Medicinal Cannabis Research McMaster University/St. Joseph's Healthcare Hamilton Hamilton Ontario Canada
| | - Pamela A.F. Madden
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Hermine H. Maes
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
| | - Patrik K.E. Magnusson
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Elliot C. Nelson
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Markus M. Nöthen
- Institute of Human Genetics University of Bonn School of Medicine & University Hospital Bonn Bonn Germany
| | - Abraham A. Palmer
- Department of Psychiatry University of California San Diego La Jolla California USA
- Institute for Genomic Medicine University of California San Diego La Jolla California USA
| | - Brenda W.J.H. Penninx
- Department of Psychiatry, Amsterdam UMC VU University and GGZinGeest Amsterdam The Netherlands
| | - Bernice Porjesz
- Department of Psychiatry and Behavioral Sciences, Henri Begleiter Neurodynamics Laboratory SUNY Downstate Medical Center Brooklyn New York USA
| | - John P. Rice
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University Mannheim Germany
| | - Brien P. Riley
- Virginia Commonwealth University Alcohol Research Center Virginia Commonwealth University Richmond Virginia USA
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Richard J. Rose
- Department of Psychological & Brain Sciences Indiana University Bloomington Bloomington Indiana USA
| | - Pei‐Hong Shen
- Laboratory of Neurogenetics NIH/NIAAA Bethesda Maryland USA
| | - Judy Silberg
- Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University Richmond Virginia USA
- Department of Psychiatry Virginia Commonwealth University Richmond Virginia USA
| | - Michael C. Stallings
- Institute for Behavioral Genetics University of Colorado Boulder Boulder Colorado USA
| | - Ralph E. Tarter
- School of Pharmacy University of Pittsburgh Pittsburgh Pennsylvania USA
| | | | - Scott Vrieze
- Department of Psychology University of Minnesota Minneapolis Minnesota USA
| | - Tamara L. Wall
- Department of Psychiatry University of California San Diego La Jolla California USA
| | - John B. Whitfield
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
| | - Hongyu Zhao
- Department of Biostatistics, Yale School of Public Health Yale University New Haven Connecticut USA
| | - Benjamin M. Neale
- Analytic and Translational Genetics Unit, Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA
- Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge Massachusetts USA
| | - Tracey D. Wade
- School of Psychology Flinders University Adelaide South Australia Australia
| | - Andrew C. Heath
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
| | - Grant W. Montgomery
- QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
- Institute for Molecular Bioscience University of Queensland Brisbane Queensland Australia
- Queensland Brain Institute University of Queensland Brisbane Queensland Australia
| | | | - Patrick F. Sullivan
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Department of Genetics University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
| | - Jaakko Kaprio
- Department of Public Health University of Helsinki Helsinki Finland
- Institute for Molecular Medicine FIMM, HiLIFE University of Helsinki Helsinki Finland
| | - Gerome Breen
- Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
- National Institute for Health Research Biomedical Research Centre King's College London and South London and Maudsley National Health Service Trust London UK
| | - Joel Gelernter
- Department of Psychiatry, Division of Human Genetics Yale School of Medicine New Haven Connecticut USA
- Veterans Affairs Connecticut Healthcare System West Haven Connecticut USA
- Department of Genetics Yale School of Medicine New Haven Connecticut USA
- Department of Neuroscience Yale School of Medicine New Haven Connecticut USA
| | - Howard J. Edenberg
- Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis Indiana USA
- Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA
| | - Cynthia M. Bulik
- Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
- Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
- Department of Nutrition University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
| | - Arpana Agrawal
- Department of Psychiatry Washington University School of Medicine Saint Louis Missouri USA
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Ghogare A, Patil P, Vankar G. A systematic review of childhood psychological traumas and alexithymia among persons with alcohol dependence syndrome. ANNALS OF INDIAN PSYCHIATRY 2021. [DOI: 10.4103/aip.aip_54_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Godwin JW. The Fast Track intervention's impact on behaviors of despair in adolescence and young adulthood. Proc Natl Acad Sci U S A 2020; 117:31748-31753. [PMID: 33262281 PMCID: PMC7749361 DOI: 10.1073/pnas.2016234117] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
How to mitigate the dramatic increase in the number of self-inflicted deaths from suicide, alcohol-related liver disease, and drug overdose among young adults has become a critical public health question. A promising area of study looks at interventions designed to address risk factors for the behaviors that precede these -often denoted-"deaths of despair." This paper examines whether a childhood intervention can have persistent positive effects by reducing adolescent and young adulthood (age 25) behaviors that precede these deaths, including suicidal ideation, suicide attempts, hazardous drinking, and opioid use. These analyses test the impact and mechanisms of action of Fast Track (FT), a comprehensive childhood intervention designed to decrease aggression and delinquency in at-risk kindergarteners. We find that random assignment to FT significantly decreases the probability of exhibiting any behavior of despair in adolescence and young adulthood. In addition, the intervention decreases the probability of suicidal ideation and hazardous drinking in adolescence and young adulthood as well as opioid use in young adulthood. Additional analyses indicate that FT's improvements to children's interpersonal (e.g., prosocial behavior, authority acceptance), intrapersonal (e.g., emotional recognition and regulation, social problem solving), and academic skills in elementary and middle school partially mediate the intervention effect on adolescent and young adult behaviors of despair and self-destruction. FT's improvements to interpersonal skills emerge as the strongest indirect pathway to reduce these harmful behaviors. This study provides evidence that childhood interventions designed to improve these skills can decrease the behaviors associated with premature mortality.
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Affiliation(s)
- Jennifer W Godwin
- Center for Child and Family Policy, Duke University, Durham, NC 27708
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Mierzejewski P, Zakrzewska A, Kuczyńska J, Wyszogrodzka E, Dominiak M. Intergenerational implications of alcohol intake: metabolic disorders in alcohol-naïve rat offspring. PeerJ 2020; 8:e9886. [PMID: 32974100 PMCID: PMC7489241 DOI: 10.7717/peerj.9886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 08/16/2020] [Indexed: 12/18/2022] Open
Abstract
Alcohol drinking may be associated with an increased risk of various metabolic diseases. Rat lines selectively bred for alcohol preference and alcohol avoidance constitute an interesting model to study inherited factors related to alcohol drinking and metabolic disorders. The aim of the present study was to compare the levels of selected laboratory biomarkers of metabolic disorders in blood samples from naïve offspring of Warsaw alcohol high-preferring (WHP), Warsaw alcohol low-preferring (WLP), and wild Wistar rats. Blood samples were collected from 3-month old (300–350 g) alcohol-naïve, male offspring of WHP (n = 8) and WLP rats (n = 8), as well as alcohol-naïve, male, wild Wistar rats. Markers of metabolic, hepatic, and pancreatic disorders were analysed (levels of homocysteine, glucose, total cholesterol, triglycerides and γ-glutamyl transferase (GGT), aspartate (AST), alanine aminotransferase (ALT), and amylase serum activities). Alcohol-naïve offspring of WHP, WLP, and wild Wistar rats differed significantly in the levels of triglycerides, total cholesterol, homocysteine, as well as in the activity of GGT, ALT, AST, and amylase enzymes. Most markers in the alcohol-naïve offspring of WHP rats were altered even thought they were never exposed to alcohol pre- or postnatally. This may suggest that parental alcohol abuse can have a detrimental influence on offspring vulnerability to metabolic disorders.
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Affiliation(s)
- Pawel Mierzejewski
- Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Alicja Zakrzewska
- Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Julita Kuczyńska
- Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Edyta Wyszogrodzka
- Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
| | - Monika Dominiak
- Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
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Alvanzo AAH, Storr CL, Reboussin B, Green KM, Mojtabai R, La Flair LN, Cullen BA, Susukida R, Seamans M, Crum RM. Adverse childhood experiences (ACEs) and transitions in stages of alcohol involvement among US adults: Progression and regression. CHILD ABUSE & NEGLECT 2020; 107:104624. [PMID: 32683202 PMCID: PMC7968748 DOI: 10.1016/j.chiabu.2020.104624] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 06/23/2020] [Accepted: 07/05/2020] [Indexed: 05/15/2023]
Abstract
BACKGROUND Adverse childhood experiences (ACEs) are associated with a number of medical comorbidities. However, there is a paucity of data on the role ACEs play in transitions in stages of alcohol involvement. OBJECTIVE To examine the association between ACEs and transitions in alcohol problems progression and regression between No Problems, Moderate Problems and Severe Problems stages. PARTICIPANTS AND SETTING Data from 14,363 male and 19,774 female participants in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). METHODS We used latent transition analysis (LTA) with propensity score adjustment to estimate the odds of transitioning across stages of alcohol involvement, between waves, based on the number of types of ACEs experienced. We hypothesized that ACEs would be associated with increased risk of progression and decreased risk of regression. RESULTS ACEs were associated with progression to higher alcohol involvement stages, with greatest likelihood of progression from No Problems to Severe Problems for those reporting ≥3 ACEs (males: aOR = 4.78 [CI (1.84-12.44)]; females: aOR = 3.81 [CI (1.69-8.57)]). ACEs were also associated with decreased odds of regression to less problematic alcohol involvement stages, with some distinctive patterns of associations in males and in females. CONCLUSIONS This study suggests that ACEs impact transitions in alcohol involvement in both males and females, affecting both progression and regression. The association is magnified for those with multiple types of ACE exposures. These results highlight the need for prevention, early identification and intervention to mitigate the risks associated with childhood maltreatment.
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Affiliation(s)
- Anika A H Alvanzo
- Divisions of General Internal Medicine and Addiction Medicine, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, MFL- East Tower, Room E650, Baltimore, MD, 21224, USA.
| | - Carla L Storr
- Department of Family and Community Health, University of Maryland School of Nursing, Baltimore, MD, 21201, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA
| | - Beth Reboussin
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Kerry M Green
- Department of Behavioral and Community Health, University of Maryland School of Public Health, College Park, MD, 20742, USA
| | - Ramin Mojtabai
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Lareina N La Flair
- Research and Data Analysis Division, Washington State Department of Social and Health Services Olympia, WA, 98501, USA
| | - Bernadette A Cullen
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Ryoko Susukida
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA
| | - Marissa Seamans
- Department of Epidemiology, UCLA Fielding School of Public Health Los Angeles, CA, 90025, USA
| | - Rosa M Crum
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health Baltimore, MD, 21205, USA
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Scarnati MS, Boreland AJ, Joel M, Hart RP, Pang ZP. Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol. Alcohol 2020; 87:97-109. [PMID: 32561311 PMCID: PMC7958146 DOI: 10.1016/j.alcohol.2020.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/15/2020] [Accepted: 05/25/2020] [Indexed: 12/11/2022]
Abstract
The acute and chronic effects of alcohol on the brain and behavior are linked to alterations in inhibitory synaptic transmission. Alcohol's most consistent effect at the synaptic level is probably a facilitation of γ-aminobutyric acid (GABA) release, as seen from several rodent studies. The impact of alcohol on GABAergic neurotransmission in human neurons is unknown, due to a lack of a suitable experimental model. Human neurons can also be used to model effects of genetic variants linked with alcohol use disorders (AUDs). The A118G single nucleotide polymorphism (SNP rs1799971) of the OPRM1 gene encoding the N40D (D40 minor allele) mu-opioid receptor (MOR) variant has been linked with individuals who have an AUD. However, while N40D is clearly associated with other drugs of abuse, involvement with AUDs is controversial. In this study, we employed Ascl1-and Dlx2-induced inhibitory neuronal cells (AD-iNs) generated from human iPS cell lines carrying N40D variants, and investigated the impact of ethanol acutely and chronically on GABAergic synaptic transmission. We found that N40 AD-iNs display a stronger facilitation (versus D40) of spontaneous and miniature inhibitory postsynaptic current frequency in response to acute ethanol application. Quantitative immunocytochemistry of Synapsin 1+ synaptic puncta revealed a similar synapse number between N40 and D40 iNs, suggesting an ethanol modulation of presynaptic GABA release without affecting synapse density. Interestingly, D40 iNs exposed to chronic intermittent ethanol application caused a significant increase in mIPSC frequency, with only a modest enhancement observed in N40 iNs. These data suggest that the MOR genotype may confer differential sensitivity to synaptic output, which depends on ethanol exposure time and concentration for AD-iNs and may help explain alcohol dependence in individuals who carry the MOR D40 SNPs. Furthermore, this study supports the use of human neuronal cells carrying risk-associated genetic variants linked to disease, as in vitro models to assay the synaptic actions of alcohol on human neuronal cells.
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Affiliation(s)
- Matthew S Scarnati
- Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA; Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA
| | - Andrew J Boreland
- Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA; Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA
| | - Marisa Joel
- Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA; Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA
| | - Ronald P Hart
- Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA; Human Genetics Institute of New Jersey, Piscataway, NJ, 08854, USA
| | - Zhiping P Pang
- Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA; Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, 08901, USA.
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Dash GF, Martin NG, Lynskey MT, Slutske WS. Sex differences in the relative influence of marital status and parenthood on alcohol use disorder symptoms: A multilevel discordant twin design. JOURNAL OF ABNORMAL PSYCHOLOGY 2020; 129:737-747. [PMID: 32816500 DOI: 10.1037/abn0000611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Marriage and parenthood are associated with alcohol use and use disorder (AUD), although they are confounded such that many studies struggle to identify their unique and/or causal effects. The present study utilized a genetically informed discordant twin design that strengthens the putative causal role of marital and parental status in the presentation of AUD symptoms by using each individual's cotwin as their own control while simultaneously modeling both predictors among men and women. Participants were 980 complete same-sex twin pairs from the Australian Twin Registry (Mage = 31.70 [SD = 2.48]; 71% women). Marital status, parental status, and past year AUD symptoms were assessed via semistructured interview. Three random-intercept generalized linear mixed models were fit in men and women including (a) marital status only, (b) parental status only, and (c) both marital and parental status; demographics, past year pregnancy, age of first drink, age of regular drinking, personality traits, and antisociality were included as covariates. Models tested for quasi-causal and familial effects. The sole-predictor marital status model (Model 1) provided the best fit among men, while the simultaneous-predictor marital and parental status model (Model 3) provided the best fit among women. Sole-predictor models showed familial effects of both predictors among men and quasi-causal and familial effects of both predictors among women; the simultaneous-predictor model revealed familial effects of marital status only among men and quasi-causal effects of parental status only among women. The present study elucidates important sex differences in the presentation of AUD among midlife adults in the context of notable developmental milestones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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40
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Lohoff FW. Pharmacotherapies and personalized medicine for alcohol use disorder: a review. Pharmacogenomics 2020; 21:1117-1138. [PMID: 32807012 DOI: 10.2217/pgs-2020-0079] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Alcohol use disorder (AUD) is highly prevalent and among the leading causes of morbidity and mortality in the United States. Pharmacotherapies for AUD are limited, thus making identification of patient subgroups that are most likely to respond favorably crucial. In this article, pharmacogenetic research on US FDA-approved and commonly prescribed off-label medications for the treatment of AUD is comprehensively reviewed. While the field has advanced in understanding pharmacotherapies for AUD and potential genetic moderators of treatment responses, the pharmacogenetic data to guide the prescribing clinician are limited and should be interpreted with caution. Precision medicine for AUD with more beneficial treatment responses and minimal side effects remains a high priority for further research.
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Affiliation(s)
- Falk W Lohoff
- Section on Clinical Genomics & Experimental Therapeutics, National Institute on Alcohol Abuse & Alcoholism, NIH, Bethesda, MD 20892-1540, USA
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Schmitt RE, Messick MR, Shell BC, Dunbar EK, Fang H, Shelton KL, Venton BJ, Pletcher SD, Grotewiel M. Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function. Addict Biol 2020; 25:e12779. [PMID: 31169340 DOI: 10.1111/adb.12779] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Revised: 03/23/2019] [Accepted: 05/02/2019] [Indexed: 01/10/2023]
Abstract
Abuse of alcohol is a major clinical problem with far-reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol-related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast-induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet-induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol-related behavior in other species.
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Affiliation(s)
- Rebecca E. Schmitt
- Department of Human and Molecular Genetics Virginia Commonwealth University Richmond VA USA
| | - Monica R. Messick
- Department of Human and Molecular Genetics Virginia Commonwealth University Richmond VA USA
| | - Brandon C. Shell
- Department of Human and Molecular Genetics Virginia Commonwealth University Richmond VA USA
| | - Ellyn K. Dunbar
- Department of Human and Molecular Genetics Virginia Commonwealth University Richmond VA USA
| | - Huai‐Fang Fang
- Department of Chemistry and Neuroscience Graduate Program University of Virginia Charlottesville VA USA
| | - Keith L. Shelton
- Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond VA USA
| | - B. Jill Venton
- Department of Chemistry and Neuroscience Graduate Program University of Virginia Charlottesville VA USA
| | - Scott D. Pletcher
- Department of Molecular and Integrative Physiology and Geriatrics Center University of Michigan Ann Arbor MI USA
| | - Mike Grotewiel
- Department of Human and Molecular Genetics Virginia Commonwealth University Richmond VA USA
- Virginia Commonwealth University Alcohol Research Center Richmond VA USA
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Richardson GB, Boutwell BB. Decomposition of Mean Sex Differences in Alcohol Use Within a Genetic Factor Model. Behav Genet 2020; 50:320-331. [PMID: 32556750 DOI: 10.1007/s10519-020-10004-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 06/13/2020] [Indexed: 11/26/2022]
Abstract
A wealth of literature suggests that normative and heavy alcohol consumption continue to follow a historical pattern of greater prevalence among males as compared to females. Some prior research suggested that sex-specific factors might explain some of this gender gap. Generally speaking, though, more recent studies have indicated that the sources of differences for most complex traits, both genetic and environmental, are similar for males and females. To the best of our knowledge, however, no studies have tested whether genetic and environmental factors common to both sexes are more often expressed in males, on average, thereby accounting for some of the mean sex difference in alcohol use. The current study used nationally representative data from American twin respondents and a multiple group genetic factor model with a mean structure to address this gap in the literature. Results provide no evidence of sex differences in covariance structure and suggest that genetic and nonshared environmental influences common to both sexes largely explain why male alcohol use is more frequent and severe, on average, than is female use. In contrast, shared environmental influences seem to play a less important role. We discuss our findings in the context of the existing literature and chart out directions for future research.
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Affiliation(s)
- George B Richardson
- School of Human Services, College of Education, Criminal Justice, and Human Services, University of Cincinnati, 460R Teachers-Dyer Complex, Cincinnati, OH, USA.
| | - Brian B Boutwell
- School of Applied Sciences, The University of Mississippi, Jackson, MS, USA
- John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS, USA
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Dash GF, Davis CN, Martin NG, Statham DJ, Lynskey MT, Slutske WS. High-Intensity Drinking in Adult Australian Twins. Alcohol Clin Exp Res 2020; 44:522-531. [PMID: 31943258 DOI: 10.1111/acer.14262] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 11/29/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Many adult drinkers consume far beyond the binge threshold. This "high-intensity drinking" (HID), defined as 2 (HID-2) and 3 (HID-3) times the binge threshold, is of public health interest due to its role in acute alcohol-related harms. Research on HID has mostly been limited to college-aged young adults, focused on contextual factors, and neglected the potential role of genetic influences on the propensity to engage in HID. METHODS Structured diagnostic interviews assessing past-year alcohol involvement were conducted with 3,785 individuals (1,365 men, 2,420 women; Mage = 32, range = 21 to 46), including 3,314 twins and 471 nontwin siblings from the Australian Twin Registry. Multinomial logistic regression analyses were conducted to compare HID-2 and HID-3 to binge drinking on demographic correlates, drinking characteristics, and drinking-related consequences. Biometric modeling was conducted to estimate the role of genetic, common, and individual-specific environmental factors in HID propensity. RESULTS Among past-year drinkers, the prevalence of HID-2 and HID-3 was both 22%, with men disproportionally represented. The frequencies of drinking, intoxication, and binge drinking significantly increased across the heavier drinking categories, which also evidenced higher average consumption quantities and higher rates of alcohol-related consequences. The propensity to engage in HID was significantly heritable (A = 37% [95% CI: 28 to 46%]), with individual-specific environmental influences accounting for the remainder of the variance. CONCLUSIONS This study convincingly demonstrates that HID is not restricted to college-aged young adults, but also can be highly prevalent among those of working age, and that the propensity to engage in HID is partially explained by genetic influences.
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Affiliation(s)
- Genevieve F Dash
- From the, Department of Psychological Sciences, (GFD, CND, WSS), University of Missouri- Columbia, Columbia, Missouri
| | - Christal N Davis
- From the, Department of Psychological Sciences, (GFD, CND, WSS), University of Missouri- Columbia, Columbia, Missouri
| | - Nicholas G Martin
- Queensland Institute of Medical Research (QIMR) Berghofer, (NGM), Brisbane, QLD, Australia
| | - Dixie J Statham
- Department of Psychology, (DJS), Federation University, Ballarat, Vic., Australia
| | - Michael T Lynskey
- Department of Addictions, (MTL), King's College London Institute of Psychiatry, Psychology and Neuroscience, London, UK
| | - Wendy S Slutske
- From the, Department of Psychological Sciences, (GFD, CND, WSS), University of Missouri- Columbia, Columbia, Missouri
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Rhew IC, Fleming CB, Tsang S, Horn E, Kosterman R, Duncan GE. Neighborhood Deprivation Moderates Shared and Unique Environmental Influences on Hazardous Drinking: Findings from a Cross-Sectional Co-Twin Study. Subst Use Misuse 2020; 55:1625-1632. [PMID: 32326868 PMCID: PMC7485221 DOI: 10.1080/10826084.2020.1756332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Background: There has been increased interest in the interplay of genetic and environmental factors in the development of problematic alcohol use, including socioeconomic conditions of the neighborhood. Using a co-twin design, we examined the extent to which contributions of genetic, shared environmental, and unique environmental influences on hazardous drinking differed according to levels of neighborhood socioeconomic deprivation. Method: Data came from 1,521 monozygotic (MZ) and 609 dizygotic (DZ) twin pairs surveyed in Washington State. A measure of neighborhood deprivation was created based on census-tract-level variables and the Alcohol Use Disorders Identification Test 3-item instrument was used to assess level of hazardous drinking. We tested a series of nested structural equation models to examine associations among hazardous drinking, neighborhood deprivation, and the variance components (genetic [A], shared [C] and unique environmental [E] influences) of these two constructs, testing for both main effects and moderation by neighborhood deprivation. Results: Neighborhood deprivation was significantly associated with increased hazardous drinking, after accounting for A and C variance common to both phenotypes. Adjusting for within-pair differences in income and education, neighborhood deprivation moderated the magnitude of variance components of hazardous drinking, with the variance attributable to shared environment and non-shared environment increasing in more deprived neighborhoods. Conclusions: Findings point to amplification of early childhood as well as unique adulthood environmental risk on hazardous drinking in areas of greater deprivation.
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Affiliation(s)
- Isaac C Rhew
- Department of Psychiatry and Behavioral Sciences, Center for the Study of Health and Risk Behaviors, University of Washington, Seattle, Washington, USA
| | - Charles B Fleming
- Department of Psychiatry and Behavioral Sciences, Center for the Study of Health and Risk Behaviors, University of Washington, Seattle, Washington, USA
| | - Siny Tsang
- Health Education and Research Building, Washington State University, Washington State Twin Registry, Spokane, Washington, USA
| | - Erin Horn
- Department of Psychology, University of Virginia, Charlottesville, Virginia, USA
| | - Rick Kosterman
- Social Development Research Group, University of Washington, Seattle, Washington, USA
| | - Glen E Duncan
- Health Education and Research Building, Washington State University, Washington State Twin Registry, Spokane, Washington, USA
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Association Study of OPRM1 Gene in a Sample of Schizophrenia Patients With Alcohol Dependence or Abuse. CANADIAN JOURNAL OF ADDICTION 2019; 10:30-34. [DOI: 10.1097/cxa.0000000000000069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Chang LH, Whitfield JB, Liu M, Medland SE, Hickie IB, Martin NG, Verhulst B, Heath AC, Madden PA, Statham DJ, Gillespie NA. Associations between polygenic risk for tobacco and alcohol use and liability to tobacco and alcohol use, and psychiatric disorders in an independent sample of 13,999 Australian adults. Drug Alcohol Depend 2019; 205:107704. [PMID: 31731259 DOI: 10.1016/j.drugalcdep.2019.107704] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 09/18/2019] [Accepted: 10/21/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Substance use, substance use disorders (SUDs), and psychiatric disorders commonly co-occur. Genetic risk common to these complex traits is an important explanation; however, little is known about how polygenic risk for tobacco or alcohol use overlaps the genetic risk for the comorbid SUDs and psychiatric disorders. METHODS We constructed polygenic risk scores (PRSs) using GWAS meta-analysis summary statistics from a large discovery sample, GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN), for smoking initiation (SI; N = 631,564), age of initiating regular smoking (AI; N = 258,251), cigarettes per day (CPD; N = 258,999), smoking cessation (SC; N = 312,273), and drinks per week (DPW; N = 527,402). We then estimated the fixed effect of these PRSs on the liability to 15 phenotypes related to tobacco and alcohol use, substance use disorders, and psychiatric disorders in an independent target sample of Australian adults. RESULTS After adjusting for multiple testing, 10 of 75 combinations of discovery and target phenotypes remained significant. PRS-SI (R2 range: 1.98%-5.09 %) was positively associated with SI, DPW, and with DSM-IV and FTND nicotine dependence, and conduct disorder. PRS-AI (R2: 3.91 %) negatively associated with DPW. PRS-CPD (R2: 1.56 %-1.77 %) positively associated with DSM-IV nicotine dependence and conduct disorder. PRS-DPW (R2: 3.39 %-6.26 %) positively associated with only DPW. The variation of DPW was significantly influenced by sex*PRS-SI, sex*PRS-AI and sex*PRS-DPW. Such interaction effect was not detected in the other 14 phenotypes. CONCLUSIONS Polygenic risks associated with tobacco use are also associated with liability to alcohol consumption, nicotine dependence, and conduct disorder.
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Affiliation(s)
- Lun-Hsien Chang
- Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; Faculty of Medicine, the University of Queensland, 20 Weightman St, Herston QLD 4006, Australia.
| | - John B Whitfield
- Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia.
| | - Mengzhen Liu
- Department of Psychology, University of Minnesota Twin Cities, 75 E River Rd, Minneapolis, MN 55455, USA.
| | - Sarah E Medland
- Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia.
| | - Ian B Hickie
- Brain and Mind Centre, University of Sydney, 94 Mallett St, Camperdown NSW 2050, USA.
| | - Nicholas G Martin
- Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia.
| | - Brad Verhulst
- Department of psychology, Michigan State University, 316 Physics Road #262, East Lansing, MI 48824, USA.
| | - Andrew C Heath
- Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
| | - Pamela A Madden
- Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
| | - Dixie J Statham
- School of Health and Life Sciences, Federation University, Federation University Australia, PO Box 663, Ballarat, VIC 3353, Australia.
| | - Nathan A Gillespie
- Virginia Institute for Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
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Geographic gender differences in traumatic unintentional injury hospitalization and youth drinking. Drug Alcohol Depend 2019; 205:107701. [PMID: 31726428 DOI: 10.1016/j.drugalcdep.2019.107701] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/13/2019] [Accepted: 10/15/2019] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Few studies have used both spatial and non-spatial techniques to the study of alcohol outcomes. The objectives of this study were to identify clusters of traumatic unintentional injury hospitalizations by gender and blood alcohol concentration (BAC), and to determine trends and correlates by BAC levels. METHODS State Trauma Registry data capturing unintentional injuries for those aged 10 to 24 hospitalized with negative and positive BAC levels (n = 6233) were analyzed from 2006 to 2015 for all Chicago block groups. Spatial clustering techniques were applied to detect spatial clusters and Generalized Estimating Equations to determine correlates and trends while controlling for correlation within block groups. RESULTS Regardless of BAC level, hospitalization rates decreased for all age groups between 2006 to 2010 and 2011 to 2015 from 94.41 to 67.69 per 100,000 population. The decline for males hospitalized with positive BAC was 1.4 times greater than the decline for their female counterparts. Risk factors included being male, black or of a minority race, having no private insurance and living in a disadvantaged neighborhood. Male hospitalization rates clustered among 33 census block groups located in three Chicago Community Areas. No clustering was detected for female patients. Motor vehicle accidents were the leading cause of hospitalization. CONCLUSIONS Hospitalizations are decreasing in Chicago, yet the risk is concentrated, with greater decreasing rates among males than females. Spatial approaches can be valuable tools in analyzing substance abuse outcomes, to identify high-risk areas and shifts in risk within a large geographic area.
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Zaso MJ, Goodhines PA, Wall TL, Park A. Meta-Analysis on Associations of Alcohol Metabolism Genes With Alcohol Use Disorder in East Asians. Alcohol Alcohol 2019; 54:216-224. [PMID: 30834931 DOI: 10.1093/alcalc/agz011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 01/27/2019] [Accepted: 02/21/2019] [Indexed: 12/20/2022] Open
Abstract
AIMS The current meta-analysis tested independent and composite associations of three commonly studied alcohol metabolism alleles with alcohol use disorder (AUD) within East Asians as well as characterized potential moderating factors in these associations. METHODS For meta-analysis, 32 articles were selected that investigated ALDH2 (n = 17,755), ADH1B (n = 13,591) and ADH1C (n = 4,093) associations with AUD in East Asians. RESULTS AND CONCLUSIONS All three variants were associated with AUD across allelic and genotypic models: ALDH2, ORs = 0.25, P < 0.001; ADH1B, ORs = 0.22-0.49, P < 0.001; ADH1C, ORs = 0.26-0.46, P < 0.001. Composite analyses suggested genetic associations did not differ across ALDH2*2 and ADH1B*2, correcting for multiple comparisons. Moderation analyses suggested ADH1B was more strongly associated with AUD among samples with cases recruited from treatment than the community. Also, strength of ALDH2 and/or ADH1B associations varied with mean age and proportion of men in cases and controls. Findings support medium to large and unique associations of ALDH2, ADH1B, and ADH1C with AUD in East Asians. Results also identified novel methodological and sample characteristics that may modulate strength of these associations.
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Affiliation(s)
- Michelle J Zaso
- Department of Psychology, Syracuse University, 430 Huntington Hall, Syracuse, NY, USA
| | - Patricia A Goodhines
- Department of Psychology, Syracuse University, 430 Huntington Hall, Syracuse, NY, USA
| | - Tamara L Wall
- Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.,V.A. San Diego Health System, 3350 La Jolla Village Drive, San Diego, CA, USA
| | - Aesoon Park
- Department of Psychology, Syracuse University, 430 Huntington Hall, Syracuse, NY, USA
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Schermer JA, Kfrerer ML, Lynskey MT. Alcohol dependence and humor styles. CURRENT PSYCHOLOGY 2019. [DOI: 10.1007/s12144-019-00508-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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McCutcheon VV, Bucholz KK, Houston-Ludlam A, Heath AC. Elevated maternal and child mortality among women with multiple DUI convictions compared with socio-demographically matched controls. Addiction 2019; 114:1981-1991. [PMID: 31351443 PMCID: PMC6800795 DOI: 10.1111/add.14762] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 12/06/2018] [Accepted: 07/23/2019] [Indexed: 11/30/2022]
Abstract
AIMS To assess whether having multiple convictions for driving while under the influence of alcohol (MDUI) in women is a risk factor for maternal, infant and child mortality. DESIGN Retrospective cohort design using record linkage, comparing women with MDUI convictions with propensity-matched women without alcohol-related driving offences ascertained through state records, on rates of maternal, infant and child mortality. SETTING Missouri, United States. PARTICIPANTS MDUI women (n = 1658) and women with no alcohol-related driving convictions (control, n = 184 252) who gave birth from 2000 to 2004. MEASUREMENTS Data were obtained from state administrative records and US Census data. The outcomes were maternal, infant and child mortality. The input variable was presence or absence of MDUI convictions. Propensity-matching variables were maternal (smoking during pregnancy, delayed prenatal care, previous child deaths, age at birth, mother Missouri-born, education, pre-pregnancy obesity, marital status), reproductive partner (un-named partner, race/ethnicity, education, DUI status) and census tract (socio-economic advantage, urbanicity) characteristics. FINDINGS Women with MDUI convictions had higher odds of maternal, infant and child mortality than propensity-matched controls [odds ratio (OR) = 2.65, 95% confidence interval (CI) = 2.07-3.40 and OR = 1.75, 95% CI = 1.17-2.61, respectively]. CONCLUSIONS Having multiple convictions for driving under the influence of alcohol in women appears to be a risk factor for increased maternal, infant and child mortality.
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Affiliation(s)
- Vivia V. McCutcheon
- Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO 63110
| | - Kathleen K. Bucholz
- Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO 63110
| | - Alexandra Houston-Ludlam
- Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO 63110
| | - Andrew C. Heath
- Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8134, St. Louis, MO 63110
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