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Freeman J, Salberg S, Noel M, Mychasiuk R. Examining the epigenetic transmission of risk for chronic pain associated with paternal post-traumatic stress disorder: a focus on veteran populations. Transl Psychiatry 2025; 15:42. [PMID: 39910041 PMCID: PMC11799465 DOI: 10.1038/s41398-025-03267-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 01/13/2025] [Accepted: 01/30/2025] [Indexed: 02/07/2025] Open
Abstract
Chronic pain is a public health problem that significantly reduces quality of life. Although the aetiology is often unknown, recent evidence suggests that susceptibility can be transmitted intergenerationally, from parent to child. Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder, often associated with chronic pain, that has high prevalence rates in military personnel and Veterans. Therefore, we aimed to characterise the epigenetic mechanisms by which paternal trauma, such as PTSD, is transmitted across generations to confer risk in the next generation, specifically focusing on Veterans where possible. Numerous overlapping neurological pathways are implicated in both PTSD and chronic pain; many of which are susceptible to epigenetic modification, such as DNA methylation, histone modifications, and RNA regulation. Hence, epigenetic changes related to pain perception, inflammation, and neurotransmission may influence an individual's predisposition to chronic pain conditions. We also examine the effects of PTSD on parenting behaviours and discuss how these variations could impact the development of chronic pain in children. We highlight the need for further research regarding the interactions between paternal trauma and epigenetic processes to ultimately generate effective prevention and therapeutic strategies for Veterans who have been affected by PTSD and chronic pain.
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Affiliation(s)
- James Freeman
- Department of Neuroscience, Monash University, Melbourne, VIC, Australia
| | - Sabrina Salberg
- Department of Neuroscience, Monash University, Melbourne, VIC, Australia
| | - Melanie Noel
- Department of Psychology, University of Calgary, Calgary, AB, Canada
| | - Richelle Mychasiuk
- Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
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2
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Puosi E, Karlsson H, Lukkarinen H, Karlsson L, Lukkarinen M. Paternal adverse childhood experiences are associated with a low risk of atopy in the offspring. Acta Paediatr 2024; 113:2438-2451. [PMID: 38992923 DOI: 10.1111/apa.17345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/13/2024]
Abstract
AIM Parental adverse childhood experiences (ACE) might affect the offspring health through intergenerational inheritance. The aim of this study was to investigate how paternal ACE associate with offspring sensitisation and allergic rhinitis (AR). METHODS The study included 590 Finnish father-child dyads from the FinnBrain Birth Cohort Study. Outcomes were offspring sensitisation against allergens and AR at age 5.5 years. Paternal ACE up to 18 years were assessed using the Trauma and Distress Scale (TADS) with the lowest quarter as the reference group. RESULTS Of the children, 317 (54%) were males. Sensitisation occurred in 162/533 (30%) and AR in 122/590 (21%). Paternal TADS (median 17 points; interquartile range 11-27) was inversely associated with the risk of sensitisation. Children whose fathers scored the highest quarter had the lowest risk of sensitisation (adjusted odds ratio 0.42; 95% confidence interval 0.24-0.75), followed by those in the second highest quarter (0.58; 0.34-0.99). The association between the highest quarter and reduced risk of AR was similar. CONCLUSION Paternal ACE were associated with a low risk of offspring sensitisation and AR, suggesting paternal childhood stress might influence immune responses in their offspring.
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Affiliation(s)
- Emma Puosi
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Tyks Department of Paediatrics and Adolescent Medicine, Turku University Hospital and Paediatrics and Adolescent Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
| | - Hasse Karlsson
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
- Psychiatry, Department of Clinical Medicine, Faculty of Medicine, University of Turku and Tyks Psychiatry, Turku University Hospital, Turku, Finland
| | - Heikki Lukkarinen
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Tyks Department of Paediatrics and Adolescent Medicine, Turku University Hospital and Paediatrics and Adolescent Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
| | - Linnea Karlsson
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Tyks Department of Paediatrics and Adolescent Medicine, Turku University Hospital and Paediatrics and Adolescent Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
| | - Minna Lukkarinen
- FinnBrain Birth Cohort Study, Turku Brain and Mind Center, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Tyks Department of Paediatrics and Adolescent Medicine, Turku University Hospital and Paediatrics and Adolescent Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Turku, Finland
- Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
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Meredith Weiss S, Aydin E, Lloyd-Fox S, Johnson MH. Trajectories of brain and behaviour development in the womb, at birth and through infancy. Nat Hum Behav 2024; 8:1251-1262. [PMID: 38886534 DOI: 10.1038/s41562-024-01896-7] [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: 07/07/2023] [Accepted: 04/04/2024] [Indexed: 06/20/2024]
Abstract
Birth is often seen as the starting point for studying effects of the environment on human development, with much research focused on the capacities of young infants. However, recent imaging advances have revealed that the complex behaviours of the fetus and the uterine environment exert influence. Birth is now viewed as a punctuate event along a developmental pathway of increasing autonomy of the child from their mother. Here we highlight (1) increasing physiological autonomy and perceptual sensitivity in the fetus, (2) physiological and neurochemical processes associated with birth that influence future behaviour, (3) the recalibration of motor and sensory systems in the newborn to adapt to the world outside the womb and (4) the effect of the prenatal environment on later infant behaviours and brain function. Taken together, these lines of evidence move us beyond nature-nurture issues to a developmental human lifespan view beginning within the womb.
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Affiliation(s)
- Staci Meredith Weiss
- University of Cambridge, Department of Psychology, Cambridge, UK.
- University of Roehampton, School of Psychology, London, UK.
| | - Ezra Aydin
- University of Cambridge, Department of Psychology, Cambridge, UK
- Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Sarah Lloyd-Fox
- University of Cambridge, Department of Psychology, Cambridge, UK
| | - Mark H Johnson
- University of Cambridge, Department of Psychology, Cambridge, UK
- Centre for Brain and Cognitive Development, Birkbeck, University of London, London, UK
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4
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Cánepa ET, Berardino BG. Epigenetic mechanisms linking early-life adversities and mental health. Biochem J 2024; 481:615-642. [PMID: 38722301 DOI: 10.1042/bcj20230306] [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: 02/19/2024] [Revised: 04/22/2024] [Accepted: 04/24/2024] [Indexed: 05/15/2024]
Abstract
Early-life adversities, whether prenatal or postnatal exposure, have been linked to adverse mental health outcomes later in life increasing the risk of several psychiatric disorders. Research on its neurobiological consequences demonstrated an association between exposure to adversities and persistent alterations in the structure, function, and connectivity of the brain. Consistent evidence supports the idea that regulation of gene expression through epigenetic mechanisms are involved in embedding the impact of early-life experiences in the genome and mediate between social environments and later behavioral phenotypes. In addition, studies from rodent models and humans suggest that these experiences and the acquired risk factors can be transmitted through epigenetic mechanisms to offspring and the following generations potentially contributing to a cycle of disease or disease risk. However, one of the important aspects of epigenetic mechanisms, unlike genetic sequences that are fixed and unchangeable, is that although the epigenetic markings are long-lasting, they are nevertheless potentially reversible. In this review, we summarize our current understanding of the epigenetic mechanisms involved in the mental health consequences derived from early-life exposure to malnutrition, maltreatment and poverty, adversities with huge and pervasive impact on mental health. We also discuss the evidence about transgenerational epigenetic inheritance in mammals and experimental data suggesting that suitable social and pharmacological interventions could reverse adverse epigenetic modifications induced by early-life negative social experiences. In this regard, these studies must be accompanied by efforts to determine the causes that promote these adversities and that result in health inequity in the population.
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Affiliation(s)
- Eduardo T Cánepa
- Laboratorio de Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN, CONICET, Buenos Aires, Argentina
| | - Bruno G Berardino
- Laboratorio de Neuroepigenética y Adversidades Tempranas, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IQUIBICEN, CONICET, Buenos Aires, Argentina
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5
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Huang JL, Zhou X. Posttraumatic stress disorder symptoms among parents and adolescents following Typhoon Lekima: Examination of the mother-daughter sex matching effect. Dev Psychopathol 2024; 36:709-718. [PMID: 36734237 DOI: 10.1017/s0954579422001511] [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] [Indexed: 02/04/2023]
Abstract
This study aimed to examine the same-sex matching effect of posttraumatic stress disorder (PTSD) symptoms from parents to children and the mediating role of children' sense of security and catastrophization. Longitudinal data from 447 parent-child dyads were acquired using self-report scales. Parents (77.0% mothers; Mage = 40.15 years old) reported their PTSD symptoms 3 months after Super Typhoon Lekima, and children (55.9% girls; Mage = 13.40 years old) reported their PTSD symptoms, sense of security, and catastrophization 3 months and 15 months after the typhoon. Results showed that intrusion in mothers predicated intrusion, avoidance, and hyperarousal symptoms in daughters, while avoidance and hyperarousal in mothers predicted the same symptoms in daughters. This was not observed in any other parent-child dyads. Moreover, mothers' intrusion positively predicted daughters' PTSD symptoms via daughters' sense of security and then catastrophization, while mothers' hyperarousal showed the opposite prediction. These findings suggest that a same-sex matching effect occurs from mothers to daughters in terms of intrusion, avoidance, and hyperarousal symptoms of PTSD. Thus, clinical interventions that target daughters' PTSD symptoms should also consider mothers' intrusion and avoidance symptoms. Moreover, it may be possible to develop interventions to improve daughters' sense of security.
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Affiliation(s)
- Jia-Li Huang
- Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiao Zhou
- Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, Zhejiang, China
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6
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Nieto SJ, Kosten TA. Paternal alcohol exposure attenuates maintenance and reinstated operant responding for alcohol in the offspring of rats. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:1494-1504. [PMID: 37353981 DOI: 10.1111/acer.15136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/10/2023] [Accepted: 06/15/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND The heritability of alcohol use disorder is close to 50%, yet common genetic variants account for less than 5% of risk. The missing heritability may reflect environmental exposure in the parents prior to conception. Indeed, paternal alcohol exposure has many behavioral and biological consequences for rodent offspring. We recently found that paternal alcohol exposure attenuated the acquisition of operant alcohol self-administration in offspring of rats of both sexes. Here we test whether this effect extends to other phases of operant self-administration thought to model motivation, craving, and relapse. METHODS Wistar male rats exposed to alcohol vapors or air for 6 weeks were mated with alcohol-naïve females 8 weeks later. The adult offspring were trained to lever press for alcohol and tested under several conditions: (1) maintenance responding under a progressive ratio schedule, (2) extinction responding due to removal of the alcohol delivery contingency, (3) reinstatement of extinguished responding in the presence of alcohol-associated cues, and (4) reinitiation of lever press responding for alcohol delivery under fixed and progressive ratio schedules. RESULTS Alcohol-sired offspring showed reduced responding under the progressive ratio schedule and blunted cue-induced reinstatement of extinguished responding. Alcohol-sired offspring also emitted fewer responses during extinction sessions and did not reinitiate responding to the same extent as control-sired rats after alcohol delivery was restored. CONCLUSIONS Across all conditions, paternal alcohol exposure led to a reduction in the reinforcing effects of alcohol in offspring. These results are consistent with studies conducted with paternal cocaine exposure except that here we find effects in rats of both sexes.
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Affiliation(s)
- Steven J Nieto
- Department of Psychology, University of Houston, Houston, Texas, USA
| | - Therese A Kosten
- Department of Psychology, University of Houston, Houston, Texas, USA
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7
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Nuttman-Shwartz O. The Long-Term Effects of Living in a Shared and Continuous Traumatic Reality: The Case of Israeli Families on the Border With Gaza. TRAUMA, VIOLENCE & ABUSE 2023; 24:1387-1404. [PMID: 34962839 DOI: 10.1177/15248380211063467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
This article presents a literature review of the concept of intergenerational transmission of traumatic stress among a specific population of Israeli parents and children living near the Israeli/Gaza border, an area that can essentially be viewed as a laboratory of shared, continuous, and stressful reality resulting from ongoing political violence. The Google Scholar database was used to search only for peer-reviewed articles written in English and published between 2002 and 2020, and the particular focus of the study was Israeli families living in the "Gaza envelope": communities that have been on the receiving end of rockets and mortars from Gaza for the past 20 years. The review was based on 35 articles and sheds light on the existence of studies using a variety of perspectives (e.g., psychological, biopsychosocial, and behavioral). Findings demonstrate the effects of continuous stress situations on the family dynamic, even before birth, among this small population. In addition, they show that to understand the unique process of intergenerational trauma transmission in a shared continuous traumatic reality, it is important to adopt a comprehensive perspective so as to understand the reciprocal, long-lasting, and transgenerational effects of being exposed to traumatic stress. This perspective can be used as a basis for developing family intervention strategies that are appropriate for preventing stress outcomes that derive from living in the context of persistent violence.
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Ju LS, Morey TE, Seubert CN, Martynyuk AE. Intergenerational Perioperative Neurocognitive Disorder. BIOLOGY 2023; 12:biology12040567. [PMID: 37106766 PMCID: PMC10135810 DOI: 10.3390/biology12040567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/04/2023] [Accepted: 04/05/2023] [Indexed: 04/29/2023]
Abstract
Accelerated neurocognitive decline after general anesthesia/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem that may affect millions of patients each year. Advanced age, with its increasing prevalence of heightened stress, inflammation, and neurodegenerative alterations, is a consistent contributing factor to the development of PND. Although a strong homeostatic reserve in young adults makes them more resilient to PND, animal data suggest that young adults with pathophysiological conditions characterized by excessive stress and inflammation may be vulnerable to PND, and this altered phenotype may be passed to future offspring (intergenerational PND). The purpose of this narrative review of data in the literature and the authors' own experimental findings in rodents is to draw attention to the possibility of intergenerational PND, a new phenomenon which, if confirmed in humans, may unravel a big new population that may be affected by parental PND. In particular, we discuss the roles of stress, inflammation, and epigenetic alterations in the development of PND. We also discuss experimental findings that demonstrate the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane that interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring who have neither trauma nor anesthetic exposure (i.e., an animal model of intergenerational PND).
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Affiliation(s)
- Ling-Sha Ju
- Department of Anesthesiology, College of Medicine, University of Florida, P.O. Box 100254, JHMHC, 1600 SW Archer Road, Gainesville, FL 32610, USA
| | - Timothy E Morey
- Department of Anesthesiology, College of Medicine, University of Florida, P.O. Box 100254, JHMHC, 1600 SW Archer Road, Gainesville, FL 32610, USA
| | - Christoph N Seubert
- Department of Anesthesiology, College of Medicine, University of Florida, P.O. Box 100254, JHMHC, 1600 SW Archer Road, Gainesville, FL 32610, USA
| | - Anatoly E Martynyuk
- Department of Anesthesiology, College of Medicine, University of Florida, P.O. Box 100254, JHMHC, 1600 SW Archer Road, Gainesville, FL 32610, USA
- Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA
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9
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On making (and turning adaptive to) maladaptive aversive memories in laboratory rodents. Neurosci Biobehav Rev 2023; 147:105101. [PMID: 36804263 DOI: 10.1016/j.neubiorev.2023.105101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/03/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023]
Abstract
Fear conditioning and avoidance tasks usually elicit adaptive aversive memories. Traumatic memories are more intense, generalized, inflexible, and resistant to attenuation via extinction- and reconsolidation-based strategies. Inducing and assessing these dysfunctional, maladaptive features in the laboratory are crucial to interrogating posttraumatic stress disorder's neurobiology and exploring innovative treatments. Here we analyze over 350 studies addressing this question in adult rats and mice. There is a growing interest in modeling several qualitative and quantitative memory changes by exposing already stressed animals to freezing- and avoidance-related tests or using a relatively high aversive training magnitude. Other options combine aversive/fearful tasks with post-acquisition or post-retrieval administration of one or more drugs provoking neurochemical or epigenetic alterations reported in the trauma aftermath. It is potentially instructive to integrate these procedures and incorporate the measurement of autonomic and endocrine parameters. Factors to consider when defining the organismic and procedural variables, partially neglected aspects (sex-dependent differences and recent vs. remote data comparison) and suggestions for future research (identifying reliable individual risk and treatment-response predictors) are discussed.
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Raza Z, Hussain SF, Foster VS, Wall J, Coffey PJ, Martin JF, Gomes RSM. Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder. FRONTIERS IN EPIDEMIOLOGY 2023; 3:1066158. [PMID: 38455905 PMCID: PMC10910933 DOI: 10.3389/fepid.2023.1066158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 01/03/2023] [Indexed: 03/09/2024]
Abstract
War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential "healthy soldier effect", both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic-pituitary-adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.
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Affiliation(s)
- Zara Raza
- Research & Innovation, Blind Veterans UK, London, United Kingdom
- BRAVO VICTOR, Research & Innovation, London, United Kingdom
- Hull York Medical School, University of York, York, United Kingdom
| | - Syeda F Hussain
- Research & Innovation, Blind Veterans UK, London, United Kingdom
- BRAVO VICTOR, Research & Innovation, London, United Kingdom
| | - Victoria S Foster
- Research & Innovation, Blind Veterans UK, London, United Kingdom
- BRAVO VICTOR, Research & Innovation, London, United Kingdom
- St George's Hospital Medical School, London, United Kingdom
| | - Joseph Wall
- Hull York Medical School, University of York, York, United Kingdom
- Haxby Group Hull, General Practice Surgery, Hull, United Kingdom
| | - Peter J Coffey
- Development, Ageing and Disease, UCL Institute of Ophthalmology, University College London, London, United Kingdom
| | - John F Martin
- Centre for Cardiovascular Biology and Medicine, University College London, London, United Kingdom
| | - Renata S M Gomes
- Research & Innovation, Blind Veterans UK, London, United Kingdom
- BRAVO VICTOR, Research & Innovation, London, United Kingdom
- Northern Hub for Veterans and Military Families Research, Department of Nursing, Midwifery and Health, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom
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Švorcová J. Transgenerational Epigenetic Inheritance of Traumatic Experience in Mammals. Genes (Basel) 2023; 14:120. [PMID: 36672861 PMCID: PMC9859285 DOI: 10.3390/genes14010120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 01/04/2023] Open
Abstract
In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.
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Affiliation(s)
- Jana Švorcová
- Department of Philosophy and History of Science, Faculty of Science, Charles University, 128 00 Prague, Czech Republic
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12
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Brewerton TD. Mechanisms by which adverse childhood experiences, other traumas and PTSD influence the health and well-being of individuals with eating disorders throughout the life span. J Eat Disord 2022; 10:162. [PMID: 36372878 PMCID: PMC9661783 DOI: 10.1186/s40337-022-00696-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 11/09/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Multiple published sources from around the world have confirmed an association between an array of adverse childhood experiences (ACEs) and other traumatic events with eating disorders (EDs) and related adverse outcomes, including higher morbidity and mortality. METHODS In keeping with this Special Issue's goals, this narrative review focuses on the ACEs pyramid and its purported mechanisms through which child maltreatment and other forms of violence toward human beings influence the health and well-being of individuals who develop EDs throughout the life span. Relevant literature on posttraumatic stress disorder (PTSD) is highlighted when applicable. RESULTS At every level of the pyramid, it is shown that EDs interact with each of these proclaimed escalating mechanisms in a bidirectional manner that contributes to the predisposition, precipitation and perpetuation of EDs and related medical and psychiatric comorbidities, which then predispose to early death. The levels and their interactions that are discussed include the contribution of generational embodiment (genetics) and historical trauma (epigenetics), social conditions and local context, the ACEs and other traumas themselves, the resultant disrupted neurodevelopment, subsequent social, emotional and cognitive impairment, the adoption of health risk behaviors, and the development of disease, disability and social problems, all resulting in premature mortality by means of fatal complications and/or suicide. CONCLUSIONS The implications of these cascading, evolving, and intertwined perspectives have important implications for the assessment and treatment of EDs using trauma-informed care and trauma-focused integrated treatment approaches. This overview offers multiple opportunities at every level for the palliation and prevention of EDs and other associated trauma-related conditions, including PTSD.
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Affiliation(s)
- Timothy D Brewerton
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
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Schreiber WB, Robinson-Drummer PA. Opportunities to Discuss Diversity-Related Topics in Neuroscience Courses. JOURNAL OF UNDERGRADUATE NEUROSCIENCE EDUCATION : JUNE : A PUBLICATION OF FUN, FACULTY FOR UNDERGRADUATE NEUROSCIENCE 2022; 20:A361-A375. [PMID: 39036724 PMCID: PMC11256382 DOI: 10.59390/aoin4016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 03/31/2022] [Accepted: 04/04/2022] [Indexed: 07/23/2024]
Abstract
Diversity is a foundational topic in psychology, and APA recommends that diversity is covered across the psychology curriculum. Neuroscience courses face challenges with incorporating diversity-related topics owing to the historical lack of neuroscience research that focuses on diversity and the restricted range of diversity-related topics that neuroscience is typically associated with (i.e., health and disability status). This may limit students' learning of neuroscience's contributions towards understanding diversity. We review some specific examples of diversity-related topics that can be incorporated into neuroscience courses. These examples have been selected to include topics across the three major content domains of neuroscience (cellular/molecular, neuroanatomy/systems, and cognitive/behavioral), as well as across multiple diversity-related topics. Neuroscience instructors can use these examples to incorporate greater coverage of diversity-related topics within their courses and/or as points of inspiration for their own curricular additions. Providing systematic coverage of diversity-related topics in neuroscience courses highlights the ways neuroscience advances our understanding of human diversity and contributes to the educational objectives of psychology and neuroscience programs.
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Mbiydzenyuy NE, Hemmings SMJ, Qulu L. Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance. Front Behav Neurosci 2022; 16:977416. [PMID: 36212196 PMCID: PMC9539686 DOI: 10.3389/fnbeh.2022.977416] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Even though studies have shown that prenatal maternal stress is associated with increased reactivity of the HPA axis, the association between prenatal maternal stress and fetal glucocorticoid exposure is complex and most likely dependent on unidentified and poorly understood variables including nature and timing of prenatal insults. The precise mechanisms in which prenatal maternal stress influence neuroendocrine signaling between the maternal-placental-fetal interface are still unclear. The aim of this review article is to bring comprehensive basic concepts about prenatal maternal stress and mechanisms of transmission of maternal stress to the fetus. This review covers recent studies showing associations between maternal stress and alterations in offspring aggressive behavior, as well as the possible pathways for the “transmission” of maternal stress to the fetus: (1) maternal-fetal HPA axis dysregulation; (2) intrauterine environment disruption due to variations in uterine artery flow; (3) epigenetic modifications of genes implicated in aggressive behavior. Here, we present evidence for the phenomenon of intergenerational and transgenerational transmission, to better understands the mechanism(s) of transmission from parent to offspring. We discuss studies showing associations between maternal stress and alterations in offspring taking note of neuroendocrine, brain architecture and epigenetic changes that may suggest risk for aggressive behavior. We highlight animal and human studies that focus on intergenerational transmission following exposure to stress from a biological mechanistic point of view, and maternal stress-induced epigenetic modifications that have potential to impact on aggressive behavior in later generations.
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Affiliation(s)
- Ngala Elvis Mbiydzenyuy
- Department of Basic Science, School of Medicine, Copperbelt University, Ndola, Zambia
- Division of Medical Physiology, Biomedical Science Research Institute, Stellenbosch University, Cape Town, South Africa
- *Correspondence: Ngala Elvis Mbiydzenyuy,
| | - Sian Megan Joanna Hemmings
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Lihle Qulu
- Division of Medical Physiology, Biomedical Science Research Institute, Stellenbosch University, Cape Town, South Africa
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15
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Que nous apprenent les enfants des survivants de la shoah sur la transmission transgenerationnelle du traumatisme? EUROPEAN JOURNAL OF TRAUMA & DISSOCIATION 2022. [DOI: 10.1016/j.ejtd.2021.100249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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16
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Varela RB, Cararo JH, Tye SJ, Carvalho AF, Valvassori SS, Fries GR, Quevedo J. Contributions of epigenetic inheritance to the predisposition of major psychiatric disorders: theoretical framework, evidence, and implications. Neurosci Biobehav Rev 2022; 135:104579. [DOI: 10.1016/j.neubiorev.2022.104579] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 01/10/2022] [Accepted: 02/11/2022] [Indexed: 02/08/2023]
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17
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Affiliation(s)
- Ying Zhang
- Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Pavillon INAF, Université Laval, Québec, Québec, Canada
| | - Marc-André Sirard
- Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle, Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Pavillon INAF, Université Laval, Québec, Québec, Canada
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18
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Cook W, Kennedy TD, Chenail R, Detullio D, Edmonds WA. Exploring the Shared Experiences of Yazidis Who Survived Genocide. J Trauma Dissociation 2021; 23:1-16. [PMID: 34661501 DOI: 10.1080/15299732.2021.1989116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 08/09/2021] [Indexed: 10/20/2022]
Abstract
In August 2014, the Islamic State of Iraq (ISIS) and the Levant (ISIL) brutally attacked the Yazidi people and occupied Sinjar and other villages in Northern Iraq. The massacre of Yazidis that began in August 2014 was declared by the United Nations as genocide. To gain a better understanding and raise awareness of these atrocities, we conducted a qualitative, phenomenological study with 35 Yazidis, who survived the genocide. The aim of the study was to elucidate the Yazidis' processing of the genocide and how it affects their psychological functioning. Coding and theming were the methods used to categorize, bring meaning and identity to Yazidis'genocidal experiences. The interviews took place between April and June 2019. Data analysis of the interview transcripts revealed that Yazidis, who survived the genocide of 2014, commonly experienced 11 themes related to hopelessness, fear, loss, grief, distrust, change, advocacy, optimism, shock, intrusive memories, and guilt. Results from this study reveal the vulnerabilities of ethnic minorities at risk of being abducted, killed, raped, and displaced. Moreover, the inherent risk of future genocides is illustrated through the experiences shared by the Yazidis.
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Affiliation(s)
- Wendy Cook
- Nova Southeastern University, College of Psychology, Fort Lauderdale, USA
| | - Tom D Kennedy
- Nova Southeastern University, College of Psychology, Fort Lauderdale, USA
| | - Ron Chenail
- Nova Southeastern University, College of Arts, Humanities, and Social Sciences, Fort Lauderdale, USA
| | - David Detullio
- Nova Southeastern University, College of Psychology, Fort Lauderdale, USA
| | - W Alex Edmonds
- Nova Southeastern University, College of Education, Fort Lauderdale, USA
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19
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The Impact of Stress Within and Across Generations: Neuroscientific and Epigenetic Considerations. Harv Rev Psychiatry 2021; 29:303-317. [PMID: 34049337 DOI: 10.1097/hrp.0000000000000300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The impact of stress and trauma on biological systems in humans can be substantial. They can result in epigenetic changes, accelerated brain development and sexual maturation, and predisposition to psychopathology. Such modifications may be accompanied by behavioral, emotional, and cognitive overtones during one's lifetime. Exposure during sensitive periods of neural development may lead to long-lasting effects that may not be affected by subsequent environmental interventions. The cumulative effects of life stressors in an individual may affect offspring's methylome makeup and epigenetic clocks, neurohormonal modulation and stress reactivity, and physiological and reproductive development. While offspring may suffer deleterious effects from parental stress and their own early-life adversity, these factors may also confer traits that prove beneficial and enhance fitness to their own environment. This article synthesizes the data on how stress shapes biological and behavioral dimensions, drawing from preclinical and human models. Advances in this field of knowledge should potentially allow for an improved understanding of how interventions may be increasingly tailored according to individual biomarkers and developmental history.
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20
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Alhassen S, Chen S, Alhassen L, Phan A, Khoudari M, De Silva A, Barhoosh H, Wang Z, Parrocha C, Shapiro E, Henrich C, Wang Z, Mutesa L, Baldi P, Abbott GW, Alachkar A. Intergenerational trauma transmission is associated with brain metabotranscriptome remodeling and mitochondrial dysfunction. Commun Biol 2021; 4:783. [PMID: 34168265 PMCID: PMC8225861 DOI: 10.1038/s42003-021-02255-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 05/18/2021] [Indexed: 12/21/2022] Open
Abstract
Intergenerational trauma increases lifetime susceptibility to depression and other psychiatric disorders. Whether intergenerational trauma transmission is a consequence of in-utero neurodevelopmental disruptions versus early-life mother–infant interaction is unknown. Here, we demonstrate that trauma exposure during pregnancy induces in mouse offspring social deficits and depressive-like behavior. Normal pups raised by traumatized mothers exhibited similar behavioral deficits to those induced in pups raised by their biological traumatized mothers. Good caregiving by normal mothers did not reverse prenatal trauma-induced behaviors, indicating a two-hit stress mechanism comprising both in-utero abnormalities and early-life poor parenting. The behavioral deficits were associated with profound changes in the brain metabotranscriptome. Striking increases in the mitochondrial hypoxia marker and epigenetic modifier 2-hydroxyglutaric acid in the brains of neonates and adults exposed prenatally to trauma indicated mitochondrial dysfunction and epigenetic mechanisms. Bioinformatic analyses revealed stress- and hypoxia-response metabolic pathways in the neonates, which produced long-lasting alterations in mitochondrial energy metabolism and epigenetic processes (DNA and chromatin modifications). Most strikingly, early pharmacological interventions with acetyl-L-carnitine (ALCAR) supplementation produced long-lasting protection against intergenerational trauma-induced depression. Sammy Alhassen, Siwei Chen, et al. use mouse models to examine the effects of prenatal and postnatal stress on metabolomic and transcriptomic pathways in the brain. Their results suggest that altered mitochondrial metabolism may underlie trauma-induced behavioral deficits, and that correcting metabolism with ALCAR supplementation may protect against intergenerational transmission of traumatic stress.
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Affiliation(s)
- Sammy Alhassen
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Siwei Chen
- Department of Computer Science, School of Information and Computer Sciences, University of California, Irvine, CA, USA.,Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, CA, USA
| | - Lamees Alhassen
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Alvin Phan
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Mohammad Khoudari
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Angele De Silva
- Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA
| | - Huda Barhoosh
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Zitong Wang
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Chelsea Parrocha
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Emily Shapiro
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Charity Henrich
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Zicheng Wang
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA
| | - Leon Mutesa
- Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
| | - Pierre Baldi
- Department of Computer Science, School of Information and Computer Sciences, University of California, Irvine, CA, USA.,Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, CA, USA
| | - Geoffrey W Abbott
- Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA
| | - Amal Alachkar
- Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA. .,Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, CA, USA.
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21
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Hjort L, Rushiti F, Wang SJ, Fransquet P, P Krasniqi S, I Çarkaxhiu S, Arifaj D, Xhemaili VD, Salihu M, A Leku N, Ryan J. Intergenerational effects of maternal post-traumatic stress disorder on offspring epigenetic patterns and cortisol levels. Epigenomics 2021; 13:967-980. [PMID: 33993712 DOI: 10.2217/epi-2021-0015] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes (NR3C1, HTR3A and BNDF). No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.
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Affiliation(s)
- Line Hjort
- Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, 2100 Copenhagen, Denmark.,Department of Endocrinology, The Diabetes & Bone metabolic Research Unit, Rigshospitalet, 2100 Copenhagen, Denmark
| | - Feride Rushiti
- Kosovo Rehabilitation Center for Torture Victims, Pristina 10000, Kosovo
| | - Shr-Jie Wang
- Danish Institute Against Torture (DIGNITY), 2100 Copenhagen, Denmark
| | - Peter Fransquet
- Biological Neuropsychiatry Unit, School of Public Health & Preventive Medicine, Monash University, Melbourne 3004, Australia
| | | | - Selvi I Çarkaxhiu
- Kosovo Rehabilitation Center for Torture Victims, Pristina 10000, Kosovo
| | - Dafina Arifaj
- Kosovo Rehabilitation Center for Torture Victims, Pristina 10000, Kosovo
| | | | - Mimoza Salihu
- Kosovo Rehabilitation Center for Torture Victims, Pristina 10000, Kosovo
| | - Nazmie A Leku
- Kosovo Rehabilitation Center for Torture Victims, Pristina 10000, Kosovo
| | - Joanne Ryan
- Biological Neuropsychiatry Unit, School of Public Health & Preventive Medicine, Monash University, Melbourne 3004, Australia
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22
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Plank AC, Frey S, Basedow LA, Solati J, Canneva F, von Hörsten S, Kratz O, Moll GH, Golub Y. Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5. Transl Psychiatry 2021; 11:183. [PMID: 33758173 PMCID: PMC7988147 DOI: 10.1038/s41398-021-01293-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 01/11/2021] [Accepted: 02/01/2021] [Indexed: 11/17/2022] Open
Abstract
In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.
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Affiliation(s)
- Anne-Christine Plank
- grid.411668.c0000 0000 9935 6525Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054 Erlangen, Germany
| | - Stefan Frey
- grid.411668.c0000 0000 9935 6525Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054 Erlangen, Germany
| | - Lukas Andreas Basedow
- grid.4488.00000 0001 2111 7257Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany
| | - Jalal Solati
- grid.411668.c0000 0000 9935 6525Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054 Erlangen, Germany
| | - Fabio Canneva
- grid.5330.50000 0001 2107 3311Department Experimental Therapy, University Hospital Erlangen and Preclinical Experimental Animal Center, Friedrich-Alexander-University Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany
| | - Stephan von Hörsten
- grid.5330.50000 0001 2107 3311Department Experimental Therapy, University Hospital Erlangen and Preclinical Experimental Animal Center, Friedrich-Alexander-University Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany
| | - Oliver Kratz
- grid.411668.c0000 0000 9935 6525Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054 Erlangen, Germany
| | - Gunther H. Moll
- grid.411668.c0000 0000 9935 6525Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054 Erlangen, Germany
| | - Yulia Golub
- Department of Child and Adolescent Mental Health, University Hospital Erlangen, Schwabachanlage 6 and 10, 91054, Erlangen, Germany. .,Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
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23
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Daskalakis NP, Xu C, Bader HN, Chatzinakos C, Weber P, Makotkine I, Lehrner A, Bierer LM, Binder EB, Yehuda R. Intergenerational trauma is associated with expression alterations in glucocorticoid- and immune-related genes. Neuropsychopharmacology 2021; 46:763-773. [PMID: 33173192 PMCID: PMC8027026 DOI: 10.1038/s41386-020-00900-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/19/2020] [Accepted: 10/22/2020] [Indexed: 01/02/2023]
Abstract
Offspring of trauma survivors are more likely to develop PTSD, mood, and anxiety disorders and demonstrate endocrine and molecular alterations compared to controls. This study reports the association between parental Holocaust exposure and genome-wide gene expression in peripheral blood mononuclear cells (PBMC) from 77 Holocaust survivor offspring and 15 comparison subjects. Forty-two differentially expressed genes (DEGs) were identified in association with parental Holocaust exposure (FDR-adjusted p < 0.05); most of these genes were downregulated and co-expressed in a gene network related to immune cell functions. When both parental Holocaust exposure and maternal age at Holocaust exposure shared DEGs, fold changes were in the opposite direction. Similarly, fold changes of shared DEGs associated with maternal PTSD and paternal PTSD were in opposite directions, while fold changes of shared DEGs associated with both maternal and paternal Holocaust exposure or associated with both maternal and paternal age at Holocaust exposure were in the same direction. Moreover, the DEGs associated with parental Holocaust exposure were enriched for glucocorticoid-regulated genes and immune pathways with some of these genes mediating the effects of parental Holocaust exposure on C-reactive protein. The top gene across all analyses was MMP8, encoding the matrix metalloproteinase 8, which is a regulator of innate immunity. To conclude, this study identified a set of glucocorticoid and immune-related genes in association with parental Holocaust exposure with differential effects based on parental exposure-related factors.
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Affiliation(s)
- Nikolaos P. Daskalakis
- grid.240206.20000 0000 8795 072XDepartment of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA USA ,grid.66859.34Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA ,grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA
| | - Changxin Xu
- grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ,grid.274295.f0000 0004 0420 1184Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY USA
| | - Heather N. Bader
- grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ,grid.274295.f0000 0004 0420 1184Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY USA
| | - Chris Chatzinakos
- grid.240206.20000 0000 8795 072XDepartment of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA USA ,grid.66859.34Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
| | - Peter Weber
- grid.419548.50000 0000 9497 5095Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
| | - Iouri Makotkine
- grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ,grid.274295.f0000 0004 0420 1184Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY USA
| | - Amy Lehrner
- grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ,grid.274295.f0000 0004 0420 1184Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY USA
| | - Linda M. Bierer
- grid.59734.3c0000 0001 0670 2351Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY USA ,grid.274295.f0000 0004 0420 1184Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY USA
| | - Elisabeth B. Binder
- grid.419548.50000 0000 9497 5095Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany ,grid.189967.80000 0001 0941 6502Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA USA
| | - Rachel Yehuda
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Mental Health Care Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA.
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24
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Mullola S, Brooks-Gunn J, Elovainio M, Hakulinen C, Schneper LM, Notterman DA. Early childhood psychosocial family risks and cumulative dopaminergic sensitizing score: Links to behavior problems in U.S. 9-year-olds. J Affect Disord 2021; 280:432-441. [PMID: 33227672 PMCID: PMC7839973 DOI: 10.1016/j.jad.2020.11.026] [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: 06/23/2020] [Revised: 09/24/2020] [Accepted: 11/07/2020] [Indexed: 01/14/2023]
Abstract
BACKGROUND We examined, (a) whether in early childhood exposure to risky family environment in different domains (socioeconomic, mental, parenting practices, health behavior, and child-related risks) and accumulatively across various domains (cumulative risk) is associated with child's problem behavior at age 9, and (b) whether the association is more pronounced in children carrying cumulative dopaminergic sensitizing genotype or living in low-income families. METHODS Participants were 2,860 9-year old children (48% females; 48% Black) and their mothers from the 'Fragile Families and Child Wellbeing Study', a probability birth cohort from large U.S. cities. Mothers responded to questions on child's problem behavior (CBCL). Children responded to questions about their vandalism and substance use. RESULTS Cumulative family risk was associated with higher internalizing and externalizing behavior and higher vandalism and substance use. All domain-specific risk clusters were associated with higher internalizing behavior and, with the exception of child-related risk, with higher externalizing behavior. Mental health risks, risky parenting practices, and risky health behavior were associated with higher vandalism. Risky parenting practices were associated with higher substance use. The associations were robust to adjustment for cumulative dopaminergic sensitizing genotype. No G x E interactions with dopaminergic genotype and family SES were observed. LIMITATIONS Sample size was relatively small for genetic analysis and polygenic risk scores were not available. CONCLUSIONS Exposure to cumulative psychosocial family risks from early childhood is associated with early indicators of problem behavior in adolescence.
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Affiliation(s)
- Sari Mullola
- Columbia University, Teachers College, National Center for Children and Families (NCCF), Thorndike Hall 525 West 120th Street, Box 39 New York, NY 10027, USA; Tampere University, Faculty of Education and Culture, Main Campus Virta, Åkerlundinkatu 5, P.O. Box 700, FI-33014 Tampere University, Finland; University of Helsinki, Faculty of Educational Sciences, Siltavuorenpenger 5A, P.O. Box 9, 00014 University of Helsinki, Finland.
| | - Jeanne Brooks-Gunn
- Columbia University, Teachers College, National Center for Children and Families (NCCF), Thorndike Hall 525 West 120th Street, Box 39 New York, NY 10027, USA; Columbia University, The College of Physicians and Surgeons, New York, NY 10027, USA.
| | - Marko Elovainio
- University of Helsinki, Medical Faculty, Department of Psychology and Logopedics, Helsinki, Finland; Institute for Health and Welfare, P.O. Box 30, 00370 Helsinki, Finland.
| | - Christian Hakulinen
- University of Helsinki, Medical Faculty, Department of Psychology and Logopedics, Helsinki, Finland.
| | - Lisa M. Schneper
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
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25
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Gałecka M, Bliźniewska-Kowalska K, Maes M, Su KP, Gałecki P. Update on the neurodevelopmental theory of depression: is there any 'unconscious code'? Pharmacol Rep 2020; 73:346-356. [PMID: 33385173 PMCID: PMC7994228 DOI: 10.1007/s43440-020-00202-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 11/17/2020] [Accepted: 11/24/2020] [Indexed: 12/27/2022]
Abstract
Depression is currently one of the most common psychiatric disorders and the number of patients receiving antidepressant treatment is increasing every year. Therefore, it is essential to understand the underlying mechanisms that are associated with higher prevalence of depression. The main component leading to the change in functioning, in the form of apathy, anhedonia, lack of motivation and sleep disturbances, is stress. This is the factor that in recent decades—due to the civilization speed, dynamic technological development as well as competitiveness and competition in relationships—significantly affects the psychophysical condition, which results in an increase in the prevalence of civilization diseases, including depression. To understand the mechanism of susceptibility to this disease, one should consider the significant role of the interaction between immune and nervous systems. Their joint development from the moment of conception is a matrix of later predispositions, both associated with the mobilization of the proinflammatory pathways (TNFα, IL-1β, IL-6) and associated with psychological coping with stress. Such an early development period is associated with epigenetic processes that are strongly marked in prenatal development up to 1 year of age and determinate the characteristic phenotype for various forms of pathology, including depression. Regarding the inflammatory hypothesis of depression, interleukin 17 (IL-17), among other proinflammatory cytokines, might play an important role in the development of depressive disorders. It is secreted by Th17 cells, crossed the placental barrier and acts on the brain structures of the fetus by increasing IL-17 receptor levels and affecting the intensity of its signaling in the brain.
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Affiliation(s)
- Małgorzata Gałecka
- Department of Psychotherapy, Medical University of Lodz, Aleksandrowska 159, 91-229, Lodz, Poland.
| | | | - Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kuan-Pin Su
- An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Piotr Gałecki
- Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland
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26
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Bierer LM, Bader HN, Daskalakis NP, Lehrner A, Provençal N, Wiechmann T, Klengel T, Makotkine I, Binder EB, Yehuda R. Intergenerational Effects of Maternal Holocaust Exposure on FKBP5 Methylation. Am J Psychiatry 2020; 177:744-753. [PMID: 32312110 DOI: 10.1176/appi.ajp.2019.19060618] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE There is growing evidence that exposure to trauma prior to conception can affect offspring. The authors have reported that adult offspring of Holocaust survivors showed lower methylation of FK506 binding protein 5 (FKBP5) intron 7, site 6 compared with Jewish comparison volunteers. The present study sought to replicate this finding in a larger sample and to examine parental and offspring correlates of observed effects. METHODS Cytosine methylation was measured in blood using pyrosequencing. The independent replication sample consisted of 125 Holocaust offspring and 31 control subjects. Additional analyses, performed in a larger sample of 147 offspring and 40 control subjects that included the 31 previously studied participants, examined associations of parental trauma-related variables (i.e., sex of the exposed parent, parental posttraumatic stress disorder, age at Holocaust exposure) and offspring characteristics (i.e., childhood trauma exposure, lifetime psychiatric diagnoses, psychotropic medication use, FKBP5 rs1360780 genotype, FKBP5 gene expression, and neuroendocrine measures) with offspring FKBP5 methylation. RESULTS FKBP5 site 6 methylation was significantly lower in Holocaust offspring than in control subjects, an effect associated with maternal Holocaust exposure in childhood and with lower offspring self-reported anxiety symptoms. FKBP5 gene expression was elevated in Holocaust offspring. FKBP5 methylation was associated with indices of glucocorticoid sensitivity but not with basal FKBP5 gene expression. CONCLUSIONS This study replicates and extends the previously observed decrement in FKBP5 intron 7, site 6 methylation in Holocaust offspring. The predominance of this effect in offspring of mothers exposed during childhood implicates maternal developmental programming as a putative mechanism.
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Affiliation(s)
- Linda M Bierer
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Heather N Bader
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Nikolaos P Daskalakis
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Amy Lehrner
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Nadine Provençal
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Tobias Wiechmann
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Torsten Klengel
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Iouri Makotkine
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Elisabeth B Binder
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
| | - Rachel Yehuda
- Mental Health Care Center, James J. Peters VA Medical Center, Bronx, N.Y. (Bierer, Bader, Lehrner, Makotkine, Yehuda); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Bierer, Bader, Daskalakis, Lehrner, Makotkine, Yehuda); McLean Hospital, Harvard Medical School, Belmont, Mass. (Daskalakis, Klengel); Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Klengel); Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich (Provençal, Wiechmann, Binder); Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, and British Columbia Children's Hospital Research Institute, Vancouver, British Columbia (Provençal); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (Binder)
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Martynyuk AE, Ju LS, Morey TE, Zhang JQ. Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics. World J Psychiatry 2020; 10:81-94. [PMID: 32477904 PMCID: PMC7243620 DOI: 10.5498/wjp.v10.i5.81] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 03/18/2020] [Accepted: 03/26/2020] [Indexed: 02/05/2023] Open
Abstract
The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.
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Affiliation(s)
- Anatoly E Martynyuk
- Department of Anesthesiology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Ling-Sha Ju
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Timothy E Morey
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Jia-Qiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
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28
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Bailey C. Basic safety first: trauma-informed care in a hostile environment. BJPsych Bull 2020; 44:41-43. [PMID: 32223785 PMCID: PMC7283123 DOI: 10.1192/bjb.2019.91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 12/18/2019] [Indexed: 11/23/2022] Open
Abstract
SUMMARY This editorial introduces and reflects on a Praxis article in the trainees' section of this issue. The article, 'Assessing asylum seekers, refugees and undocumented migrants' by Waterman et al, begins with a clinical scenario describing an emergency presentation at a 'place of safety'. The authors are to be congratulated for navigating a compassionate path through the complexities of law, health and new diagnostic categories. The resources found in the article, drawing on the principles of trauma-informed care and the work of Judith Herman, can help trainees to be more confident in promoting the basic rights of survivors of trauma, which might form a first step in the re-establishment of trust and empowerment.
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Affiliation(s)
- Cate Bailey
- East London NHS Foundation Trust, UK
- Barts and the London School of Medicine, UK
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M. Nilsen F, Frank J, S. Tulve N. A Systematic Review and Meta-Analysis Investigating the Relationship between Exposures to Chemical and Non-Chemical Stressors during Prenatal Development and Childhood Externalizing Behaviors. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17072361. [PMID: 32244397 PMCID: PMC7177257 DOI: 10.3390/ijerph17072361] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 12/19/2022]
Abstract
Childhood behavioral outcomes have been linked to low quality intrauterine environments caused by prenatal exposures to both chemical and non-chemical stressors. The effect(s) from the many stressors a child can be prenatally exposed to may be influenced by complex interactive relationships that are just beginning to be understood. Chemical stressors influence behavioral outcomes by affecting the monoamine oxidase A (MAOA) enzyme, which is involved in serotonin metabolism and the neuroendocrine response to stress. Non-chemical stressors, particularly those associated with violence, have been shown to influence and exacerbate the externalizing behavioral outcomes associated with low MAOA activity and slowed serotonin metabolism. The adverse developmental effects associated with high stress and maternal drug use during pregnancy are well documented. However, research examining the combined effects of other non-chemical and chemical stressors on development and childhood outcomes as a result of gestational exposures is scarce but is an expanding field. In this systematic review, we examined the extant literature to explore the interrelationships between exposures to chemical and non-chemical stressors (specifically stressful/traumatic experiences), MAOA characteristics, and childhood externalizing behaviors. We observed that exposures to chemical stressors (recreational drugs and environmental chemicals) are significantly related to externalizing behavioral outcomes in children. We also observed that existing literature examining the interactions between MAOA characteristics, exposures to chemical stressors, and traumatic experiences and their effects on behavioral outcomes is sparse. We propose that maternal stress and cortisol fluctuations during pregnancy may be an avenue to link these concepts. We recommend that future studies investigating childhood behaviors include chemical and non-chemical stressors as well as children’s inherent genetic characteristics to gain a holistic understanding of the relationship between prenatal exposures and childhood behavioral outcomes.
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Affiliation(s)
- Frances M. Nilsen
- Oak Ridge Institute for Science and Education, U.S. Environmental Protection Agency, Office of Research and Development, 109 TW Alexander Dr., Research Triangle Park, NC 27709, USA;
- Correspondence:
| | - Jessica Frank
- Oak Ridge Institute for Science and Education, U.S. Environmental Protection Agency, Office of Research and Development, 109 TW Alexander Dr., Research Triangle Park, NC 27709, USA;
| | - Nicolle S. Tulve
- U.S. Environmental Protection Agency, Office of Research and Development, 109 TW Alexander Dr., Research Triangle Park, NC 27709, USA;
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Syme KL, Hagen EH. Mental health is biological health: Why tackling "diseases of the mind" is an imperative for biological anthropology in the 21st century. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2019; 171 Suppl 70:87-117. [PMID: 31762015 DOI: 10.1002/ajpa.23965] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 10/23/2019] [Accepted: 10/24/2019] [Indexed: 12/23/2022]
Abstract
The germ theory of disease and the attendant public health initiatives, including sanitation, vaccination, and antibiotic treatment, led to dramatic increases in global life expectancy. As the prevalence of infectious disease declines, mental disorders are emerging as major contributors to the global burden of disease. Scientists understand little about the etiology of mental disorders, however, and many of the most popular psychopharmacological treatments, such as antidepressants and antipsychotics, have only moderate-to-weak efficacy in treating symptoms and fail to target biological systems that correspond to discrete psychiatric syndromes. Consequently, despite dramatic increases in the treatment of some mental disorders, there has been no decrease in the prevalence of most mental disorders since accurate record keeping began. Many researchers and theorists are therefore endeavoring to rethink psychiatry from the ground-up. Anthropology, especially biological anthropology, can offer critical theoretical and empirical insights to combat mental illness globally. Biological anthropologists are unique in that we take a panhuman approach to human health and behavior and are trained to address each of Tinbergen's four levels of analysis as well as culture. The field is thus exceptionally well-situated to help resolve the mysteries of mental illness by integrating biological, evolutionary, and sociocultural perspectives.
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Affiliation(s)
- Kristen L Syme
- Department of Anthropology, Washington State University, Vancouver, Washington
| | - Edward H Hagen
- Department of Anthropology, Washington State University, Vancouver, Washington
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31
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Géranton SM. Does epigenetic 'memory' of early-life stress predispose to chronic pain in later life? A potential role for the stress regulator FKBP5. Philos Trans R Soc Lond B Biol Sci 2019; 374:20190283. [PMID: 31544613 DOI: 10.1098/rstb.2019.0283] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Animal behaviours are affected not only by inherited genes but also by environmental experiences. For example, in both rats and humans, stressful early-life events such as being reared by an inattentive mother can leave a lasting trace and affect later stress response in adult life. This is owing to a chemical trace left on the chromatin attributed to so-called epigenetic mechanisms. Such an epigenetic trace often has consequences, sometimes long-lasting, on the functioning of our genes, thereby allowing individuals to rapidly adapt to a new environment. One gene under such epigenetic control is FKBP5, the gene that encodes the protein FKPB51, a crucial regulator of the stress axis and a significant driver of chronic pain states. In this article, we will discuss the possibility that exposure to stress could drive the susceptibly to chronic pain via epigenetic modifications of genes within the stress axis such as FKBP5. The possibility that such modifications, and therefore, the susceptibility to chronic pain, could be transmitted across generations in mammals and whether such mechanisms may be evolutionarily conserved across phyla will also be debated. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.
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Affiliation(s)
- S M Géranton
- Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
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Batchelor V, Pang TY. HPA axis regulation and stress response is subject to intergenerational modification by paternal trauma and stress. Gen Comp Endocrinol 2019; 280:47-53. [PMID: 30981703 DOI: 10.1016/j.ygcen.2019.04.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 04/08/2019] [Accepted: 04/09/2019] [Indexed: 12/20/2022]
Abstract
There is increasing evidence that one's risk for psychiatric disturbances and metabolic syndromes is influenced by their parents' own health history, lifestyle and living environment. For example, paternal high fat diet is strongly linked to neuroendocrine dysregulation in offspring and increased risk for diabetes. The potential intergenerational impact of paternal stress has only just begun to emerge, with the initial evidence suggestive of greater risk for anxiety-related disorders. The hypothalamic-pituitary-adrenal (HPA)-axis is a key neuroendocrine signalling system involved in physiological homeostasis and stress response. In individuals, dysregulation of this system is closely associated with behavioral deficits and mood disorders. Various preclinical models of paternal stress have demonstrated robust behavioral shifts but little is known about the intergenerational modification of HPA axis function. This review will present evidence drawn from a range of laboratory mouse and rat models that the intergenerational influence of paternal stress on offspring behavioral phenotypes involve some level of HPA axis dysregulation. It makes the case that further investigations to comprehensively profile HPA axis function in offspring generations is warranted.
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Affiliation(s)
- Vicky Batchelor
- Department of Anatomy & Neuroscience, University of Melbourne, VIC 3010, Australia; Florey Institute of Neurosciences and Mental Health, University of Melbourne, VIC 3010, Australia
| | - Terence Y Pang
- Department of Anatomy & Neuroscience, University of Melbourne, VIC 3010, Australia; Florey Institute of Neurosciences and Mental Health, University of Melbourne, VIC 3010, Australia.
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Hodes M, Vostanis P. Practitioner Review: Mental health problems of refugee children and adolescents and their management. J Child Psychol Psychiatry 2019; 60:716-731. [PMID: 30548855 DOI: 10.1111/jcpp.13002] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2018] [Indexed: 11/29/2022]
Abstract
BACKGROUND Since 2010, the numbers of refugees have increased and around half are under 18 years of age. It is known that experience of organised violence, displacement and resettlement increases the risk for psychiatric disorders and psychosocial impairment. This review integrates recent research into the risk and protective factors for psychopathology with service and treatment issues. METHODS We draw on and critically evaluate key systematic reviews in the selected areas, innovative robust studies and relevant government reports. RESULTS Many refugee children show resilience and function well, even in the face of substantial adversities. The most robust findings for psychopathology are that PTSD, and posttraumatic and depressive symptoms are found at higher prevalence in those who have been exposed to war experiences. Their severity may decrease over time with resettlement, but PTSD in the most exposed may show higher continuity. More severe psychiatric disorders including psychosis may also occur. Service delivery needs to take into account socioeconomic and cultural influences but, given the high level of unmet need even in high-income countries, stepped care delivery is required. The evaluation of psychological interventions, often delivered in group settings, suggests that they can be effective for many distressed children; however, for the more impaired, a greater range of disorder-specific therapies will be required. CONCLUSIONS Child and adolescent mental health clinicians and service providers need to be aware of the specific needs of this population and systems for service delivery. There are significant knowledge gaps in understanding risk and vulnerability, service delivery and treatment effectiveness.
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Affiliation(s)
- Matthew Hodes
- Centre for Psychiatry, Imperial College London, London, UK
| | - Panos Vostanis
- Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK
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Locci A, Pinna G. Social isolation as a promising animal model of PTSD comorbid suicide: neurosteroids and cannabinoids as possible treatment options. Prog Neuropsychopharmacol Biol Psychiatry 2019; 92:243-259. [PMID: 30586627 DOI: 10.1016/j.pnpbp.2018.12.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 12/18/2018] [Accepted: 12/21/2018] [Indexed: 02/07/2023]
Abstract
Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by drastic alterations in mood, emotions, social abilities and cognition. Notably, one aspect of PTSD, particularly in veterans, is its comorbidity with suicide. Elevated aggressiveness predicts high-risk to suicide in humans and despite the difficulty in reproducing a complex human suicidal behavior in rodents, aggressive behavior is a well reproducible behavioral trait of suicide. PTSD animal models are based on a peculiar phenotype, including exaggerated fear memory and impaired fear extinction associated with neurochemical dysregulations in the brain circuitry regulating emotion. The endocannabinoid and the neurosteroid systems regulate emotions and stress responses, and recent evidence shows these two systems are interrelated and critically compromised in neuropsychiatric disorders. For instance, levels of the neurosteroid, allopregnanolone, as well as those of the endocannabinoids, anandamide and its congener, palmitoylethanolamide are decreased in PTSD. Similarly, the endocannabinoid system and neurosteroid biosynthesis are altered in suicidal individuals. Selective serotonin reuptake inhibitors (SSRIs), the only FDA-approved treatments for PTSD, fail to help half of the treatment-seeking patients. This highlights the need for developing biomarker-based efficient therapies. One promising alternative to SSRIs points to stimulation of allopregnanolone biosynthesis as a treatment and a valid end-point to predict treatment response in PTSD patients. This review highlights running findings on the role of the endocannabinoid and neurosteroid systems in PTSD and suicidal behavior both in a preclinical and clinical perspective. A specific focus is given to predictive PTSD/suicide animal models. Ultimately, we discuss the idea that disruption of neurosteroid and endocannabinoid biosynthesis may offer a novel promising biomarker axis to develop new treatments for PTSD and, perhaps, suicidal behavior.
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Affiliation(s)
- Andrea Locci
- The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, USA
| | - Graziano Pinna
- The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, USA.
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35
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Rompala GR, Homanics GE. Intergenerational Effects of Alcohol: A Review of Paternal Preconception Ethanol Exposure Studies and Epigenetic Mechanisms in the Male Germline. Alcohol Clin Exp Res 2019; 43:1032-1045. [PMID: 30908630 PMCID: PMC6551262 DOI: 10.1111/acer.14029] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/13/2019] [Indexed: 12/11/2022]
Abstract
While alcohol use disorder (AUD) is a highly heritable psychiatric disease, efforts to elucidate that heritability by examining genetic variation (e.g., single nucleotide polymorphisms) have been insufficient to fully account for familial AUD risk. Perhaps not coincidently, there has been a burgeoning interest in novel nongenomic mechanisms of inheritance (i.e., epigenetics) that are shaped in the male or female germ cells by significant lifetime experiences such as exposure to chronic stress, malnutrition, or drugs of abuse. While many epidemiological and preclinical studies have long pointed to a role for the parental preconception environment in offspring behavior, over the last decade many studies have implicated a causal relationship between the environmentally sensitive sperm epigenome and intergenerational phenotypes. This critical review will detail the heritable effects of alcohol and the potential role for epigenetics.
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Affiliation(s)
- Gregory R Rompala
- Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Gregg E Homanics
- Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School Medicine, Pittsburgh, Pennsylvania
- Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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36
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Bhattacharya S, Fontaine A, MacCallum PE, Drover J, Blundell J. Stress Across Generations: DNA Methylation as a Potential Mechanism Underlying Intergenerational Effects of Stress in Both Post-traumatic Stress Disorder and Pre-clinical Predator Stress Rodent Models. Front Behav Neurosci 2019; 13:113. [PMID: 31191267 PMCID: PMC6547031 DOI: 10.3389/fnbeh.2019.00113] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 05/07/2019] [Indexed: 12/12/2022] Open
Abstract
Although most humans will experience some type of traumatic event in their lifetime only a small set of individuals will go on to develop post-traumatic stress disorder (PTSD). Differences in sex, age, trauma type, and comorbidity, along with many other elements, contribute to the heterogenous manifestation of this disorder. Nonetheless, aberrant hypothalamus-pituitary-adrenal (HPA) axis activity, especially in terms of cortisol and glucocorticoid receptor (GR) alterations, has been postulated as a tenable factor in the etiology and pathophysiology of PTSD. Moreover, emerging data suggests that the harmful effects of traumatic stress to the HPA axis in PTSD can also propagate into future generations, making offspring more prone to psychopathologies. Predator stress models provide an ethical and ethologically relevant way to investigate tentative mechanisms that are thought to underlie this phenomenon. In this review article, we discuss findings from human and laboratory predator stress studies that suggest changes to DNA methylation germane to GRs may underlie the generational effects of trauma transmission. Understanding mechanisms that promote stress-induced psychopathology will represent a major advance in the field and may lead to novel treatments for such devastating, and often treatment-resistant trauma and stress-disorders.
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Affiliation(s)
- Sriya Bhattacharya
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Audrey Fontaine
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada.,Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie, Sorbonne Universités, Paris, France
| | - Phillip E MacCallum
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - James Drover
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Jacqueline Blundell
- Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada
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Valsamakis G, Chrousos G, Mastorakos G. Stress, female reproduction and pregnancy. Psychoneuroendocrinology 2019; 100:48-57. [PMID: 30291988 DOI: 10.1016/j.psyneuen.2018.09.031] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 09/09/2018] [Accepted: 09/18/2018] [Indexed: 12/11/2022]
Abstract
Stress is one of the commonest and underappreciated causes of reproductive frailty in women. The stress system leads to adaptive responses via mobilization of hormonal systems. Adaptability and resistance to stress are fundamental to life. The response to stressors depends on the type of stressor, the timing and duration of stress, the genetic predisposition, personality characteristics, and the way of coping with stress. The hypothalamic-pituitary-adrenal (HPA) axis has a direct inhibitory action on the hypothalamic-pituitary-ovarian (HPO) axis at multiple levels. Acute and chronic stress impairs reproduction, eventually acting on varying mechanisms. Undernutrition, over-training, and psychological stress contribute to hypothalamic amenorrhea via reduced HPO activity. In utero stress exposure is a significant predictor of subsequent adult telomere length. Some of the metabolic consequences of intrauterine growth restriction can be mitigated by ensuring early appropriate catch-up growth, while avoiding excessive weight gain if relative hypercortisolism is not installed. The effect of maternal stress on fetuses regarding fetal HPA axis responsiveness (increased or decreased) remains under investigation. Maternal stress and depression are associated with structural and functional changes of brain parts such as hippocampus. In utero stress modifies epigenetically components of the HPA axis which can be transmitted transgenerationally.
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Affiliation(s)
- Georgios Valsamakis
- Department of Endocrinology and Metabolic Disorders, University Hospital of Larissa, Medical School of Larissa, University of Thessaly, Larissa, Greece
| | - George Chrousos
- First Department of Paediatrics, Aghia Sophia University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, Athens, Greece
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, Athens, Greece.
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38
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Morgan CP, Chan JC, Bale TL. Driving the Next Generation: Paternal Lifetime Experiences Transmitted via Extracellular Vesicles and Their Small RNA Cargo. Biol Psychiatry 2019; 85:164-171. [PMID: 30580777 PMCID: PMC6309802 DOI: 10.1016/j.biopsych.2018.09.007] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 08/29/2018] [Accepted: 09/17/2018] [Indexed: 10/28/2022]
Abstract
Epidemiological studies provide strong evidence for the impact of diverse paternal life experiences on offspring neurodevelopmental disease risk. While these associations are well established, the molecular mechanisms underlying these intergenerational transmissions remain elusive, though recent studies focusing on the influence of paternal experience before conception have implicated germ cell epigenetic programming. Any model accounting for the germline transfer of nongenetic information from sire to offspring must include certain components, such as 1) a vector to carry any signal from the paternal compartment to the maternal reproductive tract and future embryo; 2) a molecular signal, encoded by a paternal experience, to carry this memory and enact downstream responses; and 3) a target cell or tissue to receive the signal and convert it into an effect on embryonic development. We explore the current understanding of the potential processes and candidate factors that may serve as these components. We specifically discuss the growing appreciation for the importance of extracellular vesicles in these processes, beginning with their known role in delivering potential signals, including small RNAs, to sperm, the prototypical vector, during their posttesticular maturation. Finally, we explore the possibility that paternal extracellular vesicles could themselves serve as vectors, delivering signals not only to gametes or the zygote but also to tissues of the maternal reproductive tract to influence fetal development.
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Affiliation(s)
- Christopher P Morgan
- Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Jennifer C Chan
- Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Tracy L Bale
- Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland.
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39
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Dashorst P, Mooren TM, Kleber RJ, de Jong PJ, Huntjens RJC. Intergenerational consequences of the Holocaust on offspring mental health: a systematic review of associated factors and mechanisms. Eur J Psychotraumatol 2019; 10:1654065. [PMID: 31497262 PMCID: PMC6720013 DOI: 10.1080/20008198.2019.1654065] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Revised: 07/14/2019] [Accepted: 07/28/2019] [Indexed: 11/24/2022] Open
Abstract
Exposure to war and violence has major consequences for society at large, detrimental impact on people's individual lives, and may also have intergenerational consequences. To gain more insight into these intergenerational consequences, research addressing the impact of the Holocaust on offspring is an important source of information. The aim of the current study was to systematically review the mechanisms of intergenerational consequences by summarizing characteristics in Holocaust survivors and their offspring suggested to impact the offspring's mental health. We focused on: 1) parental mental health problems, 2) (perceived) parenting and attachment quality, 3) family structure, especially parental Holocaust history, 4) additional stress and life events, and 5) psychophysiological processes of transmission. We identified 23 eligible studies published between 2000 and 2018. Only Holocaust survivor studies met the inclusion criteria. Various parent and child characteristics and their interaction were found to contribute to the development of psychological symptoms and biological and epigenetic variations. Parental mental health problems, perceived parenting, attachment quality, and parental gender appeared to be influential for the mental well-being of their offspring. In addition, having two survivor parents resulted in higher mental health problems compared to having one survivor parent. Also, there was evidence suggesting that Holocaust survivor offspring show a heightened vulnerability for stress, although this was only evident in the face of actual danger. Finally, the results also indicate intergenerational effects on offspring cortisol levels. Clinical and treatment implications are discussed.
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Affiliation(s)
| | - Trudy M Mooren
- Stichting Centrum'45/partner in Arq, Diemen, The Netherlands.,Department of Clinical & Health Psychology, Utrecht University, Utrecht, The Netherlands
| | - Rolf J Kleber
- Stichting Centrum'45/partner in Arq, Diemen, The Netherlands.,Department of Clinical & Health Psychology, Utrecht University, Utrecht, The Netherlands
| | - Peter J de Jong
- Department of Clinical Psychology & Experimental Psychopathology, University of Groningen, Groningen, The Netherlands
| | - Rafaele J C Huntjens
- Department of Clinical Psychology & Experimental Psychopathology, University of Groningen, Groningen, The Netherlands
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40
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Cutuli D, Berretta E, Laricchiuta D, Caporali P, Gelfo F, Petrosini L. Pre-reproductive Parental Enriching Experiences Influence Progeny's Developmental Trajectories. Front Behav Neurosci 2018; 12:254. [PMID: 30483072 PMCID: PMC6240645 DOI: 10.3389/fnbeh.2018.00254] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 10/10/2018] [Indexed: 01/09/2023] Open
Abstract
While the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring’s phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral traits.
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Affiliation(s)
- Debora Cutuli
- Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.,Fondazione Santa Lucia, Rome, Italy
| | - Erica Berretta
- Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.,Fondazione Santa Lucia, Rome, Italy
| | - Daniela Laricchiuta
- Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.,Fondazione Santa Lucia, Rome, Italy
| | - Paola Caporali
- Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.,Fondazione Santa Lucia, Rome, Italy
| | - Francesca Gelfo
- Fondazione Santa Lucia, Rome, Italy.,Department of Human Sciences, Guglielmo Marconi University, Rome, Italy
| | - Laura Petrosini
- Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.,Fondazione Santa Lucia, Rome, Italy
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Yehuda R, Lehrner A. Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms. World Psychiatry 2018; 17:243-257. [PMID: 30192087 PMCID: PMC6127768 DOI: 10.1002/wps.20568] [Citation(s) in RCA: 211] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 06/13/2018] [Accepted: 06/13/2018] [Indexed: 12/18/2022] Open
Abstract
This paper reviews the research evidence concerning the intergenerational transmission of trauma effects and the possible role of epigenetic mechanisms in this transmission. Two broad categories of epigenetically mediated effects are highlighted. The first involves developmentally programmed effects. These can result from the influence of the offspring's early environmental exposures, including postnatal maternal care as well as in utero exposure reflecting maternal stress during pregnancy. The second includes epigenetic changes associated with a preconception trauma in parents that may affect the germline, and impact fetoplacental interactions. Several factors, such as sex-specific epigenetic effects following trauma exposure and parental developmental stage at the time of exposure, explain different effects of maternal and paternal trauma. The most compelling work to date has been done in animal models, where the opportunity for controlled designs enables clear interpretations of transmissible effects. Given the paucity of human studies and the methodological challenges in conducting such studies, it is not possible to attribute intergenerational effects in humans to a single set of biological or other determinants at this time. Elucidating the role of epigenetic mechanisms in intergenerational effects through prospective, multi-generational studies may ultimately yield a cogent understanding of how individual, cultural and societal experiences permeate our biology.
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Affiliation(s)
- Rachel Yehuda
- James J. Peters Bronx Veterans Affairs Hospital, Bronx, NY, USA
- Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Amy Lehrner
- James J. Peters Bronx Veterans Affairs Hospital, Bronx, NY, USA
- Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Abstract
AbstractThe question of whether and how the effects of cultural trauma can be transmitted intergenerationally from parents to offspring, or even to later generations, has evoked interest and controversy in academic and popular forums. Recent methodological advances have spurred investigations of potential epigenetic mechanisms for this inheritance, representing an exciting area of emergent research. Epigenetics has been described as the means through which environmental influences “get under the skin,” directing transcriptional activity and influencing the expression or suppression of genes. Over the past decade, this complex environment–biology interface has shown increasing promise as a potential pathway for the intergenerational transmission of the effects of trauma. This article reviews challenges facing research on cultural trauma, biological findings in trauma and posttraumatic stress disorder, and putative epigenetic mechanisms for transmission of trauma effects, including through social, intrauterine, and gametic pathways. Implications for transmission of cultural trauma effects are discussed, focused on the relevance of cultural narratives and the possibilities of resilience and adaptivity.
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Chan JC, Nugent BM, Bale TL. Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment. Biol Psychiatry 2018; 83:886-894. [PMID: 29198470 PMCID: PMC5899063 DOI: 10.1016/j.biopsych.2017.10.005] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 09/07/2017] [Accepted: 10/03/2017] [Indexed: 12/16/2022]
Abstract
Parental stress exposures are implicated in the risk for offspring neurodevelopmental and neuropsychiatric disorders, prompting critical examination of preconception and prenatal periods as vulnerable to environmental insults such as stress. Evidence from human studies and animal models demonstrates the influence that both maternal and paternal stress exposures have in changing the course of offspring brain development. Mechanistic examination of modes of intergenerational transmission of exposure during pregnancy has pointed to alterations in placental signaling, including changes in inflammatory, nutrient-sensing, and epigenetic pathways. Transmission of preconception paternal stress exposure is associated with changes in epigenetic marks in sperm, with a primary focus on the reprogramming of DNA methylation, histone posttranslational modifications, and small noncoding RNAs. In this review, we discuss evidence supporting the important contribution of intergenerational parental stress in offspring neurodevelopment and disease risk, and the currently known epigenetic mechanisms underlying this transmission.
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Affiliation(s)
- Jennifer C Chan
- Department of Biomedical Sciences, School of Veterinary Medicine and Perelman School of Medicine University of Pennsylvania, Philadelphia, Pennsylvania
| | - Bridget M Nugent
- Department of Pharmacology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland
| | - Tracy L Bale
- Department of Pharmacology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland.
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44
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Zhang H, Peng SH, Liang XL, Wang HY, Zhang XG, Jiang XJ. Ntf3 hypermethylation in antenatal PTSD and preventive effect of the Chinese herbal medicine Jin Kui Shen Qi Wan. BIOTECHNOL BIOTEC EQ 2018. [DOI: 10.1080/13102818.2017.1421101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022] Open
Affiliation(s)
- Hui Zhang
- Section Chinese Medicine Nursing of School of Nursing, Chengdu University of TCM, Chengdu, PR China
| | - Si Han Peng
- School of Clinical Medicine, Chengdu University of TCM, Chengdu, PR China
| | - Xiao Li Liang
- Section Chinese Medicine Nursing of School of Nursing, Chengdu University of TCM, Chengdu, PR China
| | - Hong Yan Wang
- School of Nursing, Sichuan Nursing Vocational College, Chengdu, PR China
| | - Xian Geng Zhang
- Section Chinese Medicine Nursing of School of Nursing, Chengdu University of TCM, Chengdu, PR China
- School of Nursing, Sichuan Nursing Vocational College, Chengdu, PR China
| | - Xiao Jing Jiang
- Section Chinese Medicine Nursing of School of Nursing, Chengdu University of TCM, Chengdu, PR China
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45
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Lindert J, Knobler HY, Kawachi I, Bain PA, Abramowitz MZ, McKee C, Reinharz S, McKee M. Psychopathology of children of genocide survivors: a systematic review on the impact of genocide on their children`s psychopathology from five countries. Int J Epidemiol 2018; 46:246-257. [PMID: 27784741 DOI: 10.1093/ije/dyw161] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2016] [Indexed: 01/09/2023] Open
Abstract
Background : The health consequences of genocides on children of survivors are increasingly discussed but conclusions have been conflicting. Methods We systematically reviewed studies from five electronic databases (EMBASE, PILOTS, PUBMED, PsycINFO, Web of Science), which used a quantitative study design and included: (i) exposure to the genocides of Armenians in Nazi Germany, Cambodia, Rwanda and Bosnia; (ii) mental health outcomes; (iii) validated instruments; (iv) statistical tests of associations. Study quality was appraised using a quality assessment tool for genocide studies. PRISMA reporting guidelines were followed. Results From 3352 retrieved records, 20 studies with a total of 4793 participants involving 2431 children of survivors and 2362 controls met the eligibility criteria. Studies were conducted in seven countries: Australia, Canada, Italy, Israel, Norway, Rwanda and the USAs over the past seven decades, using the Genocide Studies Quality Assessment Tool. Data from the high quality studies provide no consistent evidence that children of genocide survivors are more likely to have mental health problems than comparators who were not children of genocide survivors. Conclusions Methodological characteristics were associated with findings: studies investigating random samples of genocide survivors did not find an impact of genocides on health of children of survivors. Potential confounders (e.g. recent life events, poverty) need further investigation. Future studies of the impact of genocides on mental health should report using a standardized structure, such as the quality tool used here.
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Affiliation(s)
- Jutta Lindert
- Department of Health and Social Work, University of Emden, Emden, Germany and Women`s Research Center, Brandeis University, Waltham, MA, USA
| | - Haim Y Knobler
- Jerusalem Mental Health Center, Hadassah Hebrew University Medical School, Jerusalem, Israel and Peres Academic Center, Rehovot, Israel
| | | | - Paul A Bain
- Countway Library, Harvard School of Public Health, Boston, MA, USA
| | - Moshe Z Abramowitz
- Jerusalem Mental Health Center, Hadassah Hebrew University Medical School, Jerusalem, Israel
| | - Charlotte McKee
- Department pf Political Sciences, Exeter University, Exeter, UK
| | - Shula Reinharz
- Women's Research Center, Brandeis University, Waltham, MA, USA
| | - Martin McKee
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
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46
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Yehuda R, Lehrner A, Bierer LM. The public reception of putative epigenetic mechanisms in the transgenerational effects of trauma. ENVIRONMENTAL EPIGENETICS 2018; 4:dvy018. [PMID: 30038801 PMCID: PMC6051458 DOI: 10.1093/eep/dvy018] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 05/23/2018] [Indexed: 06/08/2023]
Abstract
There has been great interest in the possibility that effects of trauma might be passed from parent to offspring through epigenetic mechanisms. This topic has stimulated discussion and controversy in the scientific literature, the popular press, and culture at large. This article describes the initial observations that have led to recent examinations of epigenetic mechanisms in association with effects of parental trauma exposure on offspring. Epigenetic research in animals has provided models for how such effects might be transmitted. However, the attribution of any specific epigenetic mechanisms in human studies of offspring of trauma survivors is premature at this time. The article describes some of the ways in which initial epigenetic findings in the offspring of trauma survivors have been represented in the popular media. Reports have ranged from overly simplistic and sensationalistic claims to global dismissals. The authors discuss the importance of clarity in language when describing epigenetic findings for lay audiences, the need to emphasize the limitations as well as the promise of research on intergenerational transmission of trauma effects, and the importance of countering popular interpretations that imply a reductionist biological determinism. Scientists have an obligation to assist in translating important research findings and nascent avenues of research to the public. It is important to recognize the ways in which this research may unintentionally be received as supporting a narrative of permanent and significant damage in offspring, rather than contributing to discussions of potential resilience, adaptability, and mutability in biological systems affected by stress.
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Affiliation(s)
- Rachel Yehuda
- James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
- Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Amy Lehrner
- James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
- Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Linda M Bierer
- James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
- Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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47
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Moog NK, Entringer S, Rasmussen JM, Styner M, Gilmore JH, Kathmann N, Heim C, Wadhwa PD, Buss C. Intergenerational Effect of Maternal Exposure to Childhood Maltreatment on Newborn Brain Anatomy. Biol Psychiatry 2018; 83:120-127. [PMID: 28842114 PMCID: PMC5723537 DOI: 10.1016/j.biopsych.2017.07.009] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Revised: 07/10/2017] [Accepted: 07/13/2017] [Indexed: 01/02/2023]
Abstract
BACKGROUND Childhood maltreatment (CM) confers deleterious long-term consequences, and growing evidence suggests some of these effects may be transmitted across generations. We examined the intergenerational effect of maternal CM exposure on child brain structure and also addressed the hypothesis that this effect may start during the child's intrauterine period of life. METHODS A prospective longitudinal study was conducted in a clinical convenience sample of 80 mother-child dyads. Maternal CM exposure was assessed using the Childhood Trauma Questionnaire. Structural magnetic resonance imaging was employed to characterize newborn global and regional brain (tissue) volumes near the time of birth. RESULTS CM exposure was reported by 35% of the women. Maternal CM exposure was associated with lower child intracranial volume (F1,70 = 6.84, p = .011), which was primarily due to a global difference in cortical gray matter (F1,70 = 9.10, p = .004). The effect was independent of potential confounding variables, including maternal socioeconomic status, obstetric complications, obesity, recent interpersonal violence, pre- and early postpartum stress, gestational age at birth, infant sex, and postnatal age at magnetic resonance imaging scan. The observed group difference between offspring of CM-exposed mothers versus nonexposed mothers was 6%. CONCLUSIONS These findings represent the first report to date associating maternal CM exposure with variation in newborn brain structure. These observations support our hypothesis of intergenerational transmission of the effects of maternal CM exposure on child brain development and suggest this effect may originate during the child's intrauterine period of life, which may have downstream neurodevelopmental consequences.
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Affiliation(s)
- Nora K. Moog
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Medical Psychology, Berlin, Germany.,Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.,Institute of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sonja Entringer
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Medical Psychology, Berlin, Germany.,University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA.,Department of Pediatrics, University of California, Irvine, School of Medicine, Orange, CA, USA
| | - Jerod M. Rasmussen
- University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA.,Department of Pediatrics, University of California, Irvine, School of Medicine, Orange, CA, USA
| | - Martin Styner
- Departments of Psychiatry and Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - John H. Gilmore
- Departments of Psychiatry and Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Norbert Kathmann
- Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.,Institute of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christine Heim
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Medical Psychology, Berlin, Germany.,Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.,Department of Biobehavioral Health, Pennsylvania State University, College of Health and Human Development, PA, USA
| | - Pathik D. Wadhwa
- University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, USA.,Department of Pediatrics, University of California, Irvine, School of Medicine, Orange, CA, USA.,Departments of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, USA
| | - Claudia Buss
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany; Development, Health, and Disease Research Program, University of California, Irvine, Irvine, California; Department of Pediatrics, School of Medicine, University of California, Irvine, Irvine, California.
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48
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McGowan PO, Matthews SG. Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response. Endocrinology 2018; 159:69-82. [PMID: 29136116 DOI: 10.1210/en.2017-00896] [Citation(s) in RCA: 138] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 11/06/2017] [Indexed: 01/06/2023]
Abstract
The early environment has a major impact on the developing embryo, fetus, and infant. Parental adversity (maternal and paternal) and glucocorticoid exposure before conception and during pregnancy have profound effects on the development and subsequent function of the hypothalamic-pituitary-adrenal axis and related behaviors. These effects are species-, sex-, and age-specific and depend on the timing and duration of exposure. The impact of these early exposures can extend across multiple generations, via both the maternal and paternal lineage, and recent studies have begun to determine the mechanisms by which this occurs. Improved knowledge of the mechanisms by which adversity and glucocorticoids program stress systems will allow development of strategies to ameliorate and/or reverse these long-term effects.
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Affiliation(s)
- Patrick O McGowan
- Department of Biological Sciences, University of Toronto, Toronto, Ontario, Canada
- Center for Environmental Epigenetics and Development, University of Toronto, Toronto, Ontario, Canada
- Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
- Department of Psychology, University of Toronto, Toronto, Ontario, Canada
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Stephen G Matthews
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
- Department of Obstetrics & Gynaecology, University of Toronto, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
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Trollope AF, Mifsud KR, Saunderson EA, Reul JMHM. Molecular and Epigenetic Mechanisms Underlying Cognitive and Adaptive Responses to Stress. EPIGENOMES 2017; 1:17. [PMID: 31921466 PMCID: PMC6952278 DOI: 10.3390/epigenomes1030017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment.
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Affiliation(s)
- Alexandra F. Trollope
- Neuro-Epigenetics Research Group, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
- Department of Anatomy, College of Medicine and Dentistry, James Cook University, Townsville 4811, Australia
| | - Karen R. Mifsud
- Neuro-Epigenetics Research Group, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
| | - Emily A. Saunderson
- Neuro-Epigenetics Research Group, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
- Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
| | - Johannes M. H. M. Reul
- Neuro-Epigenetics Research Group, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
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Shepherd-Banigan M, Kelley ML, Katon JG, Curry JF, Goldstein KM, Brancu M, Wagner HR, Fecteau TE, Van Houtven CH. Paternal history of mental illness associated with posttraumatic stress disorder among veterans. Psychiatry Res 2017; 256:461-468. [PMID: 28710975 DOI: 10.1016/j.psychres.2017.06.053] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 06/08/2017] [Accepted: 06/14/2017] [Indexed: 10/19/2022]
Abstract
This study examined the association between parent and family reported history of non-PTSD mental illness (MI), PTSD specifically, and substance use problems, and participant clinical diagnosis of PTSD. Participants were drawn from the US Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center (MIRECC) Post-Deployment Mental Health (PDMH) study (n = 3191), an ongoing multi-site cohort study of US Afghanistan and Iraq conflict era veterans. Participants who recalled a father history of PTSD had a 26-percentage point higher likelihood of meeting criteria for PTSD; while participants reporting any family history of PTSD had a 15-percentage point higher probability of endorsing symptoms consistent with PTSD. Mother history of substance use problems was associated with Veteran current PTSD, but results were sensitive to model specification. Current PTSD was not associated with family/parent history of non-PTSD mental illness, mother history of PTSD, or family/father history of substance use problems. Family history of PTSD may increase PTSD risk among veterans exposed to trauma, particularly when a father history is reported. Knowledge of family history could improve clinical decision-making for trauma-exposed individuals and allow for more effective targeting of programs and clinical services.
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Affiliation(s)
- Megan Shepherd-Banigan
- Health Services Research and Development Service, Durham VA Medical Center, Durham, NC 27701, USA.
| | - Michelle L Kelley
- Department of Psychology, Old Dominion University, 5115 Hampton Boulevard, Norfolk, VA 23529, USA; Virginia Consortium Program in Clinical Psychology, 555 Park Avenue, Norfolk, VA 23504, USA.
| | - Jodie G Katon
- Health Services Research and Development Center of Innovation for Veteran-Centered and Value Driven Care, VA Puget Sound Health Care System, Seattle, WA 98108, USA; Department of Health Services, School of Public Health, University of Washington School of Public Health, Seattle, WA 98195, USA.
| | - John F Curry
- VA Mid-Atlantic Region Mental Illness Research, Education, and Clinical Center (MIRECC), Durham VA Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
| | - Karen M Goldstein
- Health Services Research and Development Service, Durham VA Medical Center, Durham, NC 27701, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
| | - Mira Brancu
- VA Mid-Atlantic Region Mental Illness Research, Education, and Clinical Center (MIRECC), Durham VA Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
| | - H Ryan Wagner
- VA Mid-Atlantic Region Mental Illness Research, Education, and Clinical Center (MIRECC), Durham VA Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA.
| | - Teresa E Fecteau
- Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA; Durham VA Medical Center, Mental Health Service Line, Psychology Services, Durham, NC 27705, USA.
| | | | | | - Courtney H Van Houtven
- Health Services Research and Development Service, Durham VA Medical Center, Durham, NC 27701, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
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