|
1
|
Huwart SJP, Morales-Puerto N, Everard A. Gut microbiota-related neuroinflammation at the crossroad of food reward alterations: implications for eating disorders. Gut 2025:gutjnl-2024-333397. [PMID: 39961644 DOI: 10.1136/gutjnl-2024-333397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 01/28/2025] [Indexed: 03/05/2025]
Abstract
The link between gut microbiome and eating behaviours, especially palatable food intake, is a growing focus of scientific investigation. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function and neurobehavioural signalling. This review explores the role of neuroinflammation in dysregulations of food-induced reward signalling and the potential causal role of the gut microbiota on these proinflammatory processes. Particular attention is given to eating disorders (ED, specifically anorexia nervosa, binge eating disorder and bulimia nervosa) and potential links with the gut microbiota, food reward alterations and neuroinflammation. Finally, we propose gut microbiota modulation as a promising therapeutic strategy in food reward alterations and ED.
Collapse
Affiliation(s)
- Sabrina J P Huwart
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
- Walloon Excellence in Life BIOtechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
| | - Nuria Morales-Puerto
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
- Walloon Excellence in Life BIOtechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
| | - Amandine Everard
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
- Walloon Excellence in Life BIOtechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium
| |
Collapse
|
|
2
|
Doua S, Germain N, Geandrot A, Defour C, Gay A, Massoubre C, Lang F, Estour B, Galusca B. A scoping review of circulating peptides assessments in anorexia nervosa: Uncovering diversity and nuanced findings. J Proteomics 2025; 312:105370. [PMID: 39716569 DOI: 10.1016/j.jprot.2024.105370] [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: 07/10/2024] [Revised: 12/15/2024] [Accepted: 12/17/2024] [Indexed: 12/25/2024]
Abstract
Understanding biological mechanisms underlying anorexia nervosa (AN) is necessary to develop care strategies. Despite many articles dedicated to peptides assessment in AN, there is no systematic review. A scoping review of circulating peptides published in relation to AN, comparing their results with those of controls, was conducted. Embase and PubMed databases were search from 1966 to 2022 (PROSPERO CRD42022323716). All original English articles, assessing peptides in AN (except classical markers) were analyzed. 1151 studies for 207 peptides, in 486 published articles were selected, and evidences/trends in AN were compared to controls. Fifteen clusters of function gathering peptides covering physiopathological aspects of AN were identified. This scoping review revealed a large variety of circulating peptides explored in AN. Some peptides presented with convincing results and helped understanding pathophysiologic aspects. Other peptides presented with nuanced results, partly due to insufficient number of studies, multiple assay techniques, inadequate sampling time, and lack of phenotyping. Conversion from bench-to-bed remains difficult and may explain why peptides evaluations did not currently lead to specific international recommendations or tailored therapeutic/preventive strategies. Peptide evaluation in anorexia nervosa could explore secretion profiles, and test it in well-phenotyped patients with AN, to conclude for potential clinical use, and finally design therapeutic tests.
Collapse
Affiliation(s)
- Sandra Doua
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Endocrinology Department, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Natacha Germain
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Endocrinology Department, University Hospital of Saint-Etienne, Saint-Etienne, France; Eating Disorder Reference Center, University hospital of Saint-Etienne, Saint-Etienne, France.
| | - Amale Geandrot
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France
| | - Cloé Defour
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France
| | - Aurélia Gay
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Psychiatry Department, University hospital of Saint-Etienne, Saint-Etienne, France
| | - Catherine Massoubre
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Eating Disorder Reference Center, University hospital of Saint-Etienne, Saint-Etienne, France; Psychiatry Department, University hospital of Saint-Etienne, Saint-Etienne, France
| | - Francois Lang
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Eating Disorder Reference Center, University hospital of Saint-Etienne, Saint-Etienne, France; Psychiatry Department, University hospital of Saint-Etienne, Saint-Etienne, France
| | - Bruno Estour
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Endocrinology Department, University Hospital of Saint-Etienne, Saint-Etienne, France; Eating Disorder Reference Center, University hospital of Saint-Etienne, Saint-Etienne, France
| | - Bogdan Galusca
- TAPE Research Group, Jean Monnet University, Lyon University, Saint-Etienne, France; Endocrinology Department, University Hospital of Saint-Etienne, Saint-Etienne, France; Eating Disorder Reference Center, University hospital of Saint-Etienne, Saint-Etienne, France
| |
Collapse
|
|
3
|
Doua S, Germain N, Merabet M, Redouté J, Boutet C, Schneider F, Hammour A, Gay A, Massoubre C, Estour B, Galusca B. Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone. EUROPEAN EATING DISORDERS REVIEW 2025; 33:53-66. [PMID: 39032117 PMCID: PMC11617818 DOI: 10.1002/erv.3125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 05/21/2024] [Accepted: 06/29/2024] [Indexed: 07/22/2024]
Abstract
CONTEXT Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown. OBJECTIVE To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls. METHODS Twelve-point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age-matched female participants: 13 patients with anorexia nervosa restrictive-type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [11C] diprenorphin binding potential (BPND) was evaluated in AN, ANrec and controls. RESULTS Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [11C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive-type displayed lower NH [11C] diprenorphin BPND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [11C] diprenorphin BPND did not correlated with copeptin or oxytocin. CONCLUSION Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications.
Collapse
Affiliation(s)
- Sandra Doua
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Natacha Germain
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Manel Merabet
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | | | - Claire Boutet
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Imaging DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Fabien Schneider
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Imaging DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Amira Hammour
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Aurélia Gay
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Psychiatry DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Catherine Massoubre
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Psychiatry DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Bruno Estour
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| | - Bogdan Galusca
- TAPE Research GroupJean Monnet UniversityLyon UniversitySaint‐EtienneFrance
- Endocrinology DepartmentUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
- Eating Disorder Reference CenterUniversity Hospital of Saint‐EtienneSaint‐EtienneFrance
| |
Collapse
|
|
4
|
Salvato G, Sellitto M, Crottini F, Tarlarini P, Tajani M, Basilico S, Corradi E, Bottini G. Extreme weight conditions impact on the relationship between risky decision-making and interoception. Cortex 2024; 179:126-142. [PMID: 39173579 DOI: 10.1016/j.cortex.2024.07.009] [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: 12/14/2023] [Revised: 05/16/2024] [Accepted: 07/17/2024] [Indexed: 08/24/2024]
Abstract
Anorexia nervosa (AN) and obesity (OB) lie on the two ends of the broad spectrum of extreme weight conditions (EWC). Both disorders entail the constant risk to one's body integrity. Importantly, risk-taking is supported by internal signals, the perception of which is typically distorted in EWC. In this study, we sought to characterize in EWC: (i) risky decision-making by contrasting situations in which people process bodies or neutral objects and (ii) the relationship between interoceptive ability and risky decision-making. In a between-subject design, participants with AN restricting type, participants with class 2 OB, and two groups of matched healthy controls (HC) (total N = 160) were administered either the Balloon Analogue Risk Task (BART) or a modified version of it by using a body-related stimulus as a cue in the place of the balloon. Moreover, we collected a measure of interoceptive sensibility and a measure of interoceptive accuracy. Results showed that, when analysing the global population as a continuum based on the BMI, the risk propensity decreased as a function of increased BMI, only for the task involving a body-related stimulus. Moreover, while HC risk propensity toward a body-related stimulus correlated with interoceptive sensibility, such correlation was absent in participants with AN. Individuals with OB, on the opposite pole, showed mixed interaction between interoception and risky decision-making in both tasks. These findings add one more tile to understanding these complex pathologies in the EWC spectrum, opening up future differential rehabilitation scenarios.
Collapse
Affiliation(s)
- Gerardo Salvato
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; NeuroMi, Milan Center for Neuroscience, Milan, Italy; Cognitive Neuropsychology Centre, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy.
| | - Manuela Sellitto
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; NeuroMi, Milan Center for Neuroscience, Milan, Italy; Cognitive Neuropsychology Centre, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy.
| | - Francesco Crottini
- NeuroMi, Milan Center for Neuroscience, Milan, Italy; Cognitive Neuropsychology Centre, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy; School of Advanced Studies, IUSS, Pavia, Italy
| | - Patrizia Tarlarini
- S.C. Dietetica e Nutrizione Clinica, Centro per il Trattamento dei Disturbi del Comportamento Alimentare, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy
| | - Marcella Tajani
- Dipartimento di Salute Mentale e delle Dipendenze, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy
| | - Stefania Basilico
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; NeuroMi, Milan Center for Neuroscience, Milan, Italy; Cognitive Neuropsychology Centre, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy
| | - Ettore Corradi
- S.C. Dietetica e Nutrizione Clinica, Centro per il Trattamento dei Disturbi del Comportamento Alimentare, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy
| | - Gabriella Bottini
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; NeuroMi, Milan Center for Neuroscience, Milan, Italy; Cognitive Neuropsychology Centre, ASST "Grande Ospedale Metropolitano" Niguarda, Milan, Italy
| |
Collapse
|
|
5
|
Conn K, Milton LK, Huang K, Munguba H, Ruuska J, Lemus MB, Greaves E, Homman-Ludiye J, Oldfield BJ, Foldi CJ. Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms. Mol Psychiatry 2024; 29:3291-3304. [PMID: 38678087 PMCID: PMC11449803 DOI: 10.1038/s41380-024-02575-9] [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: 12/13/2023] [Revised: 04/16/2024] [Accepted: 04/19/2024] [Indexed: 04/29/2024]
Abstract
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.
Collapse
MESH Headings
- Animals
- Female
- Psilocybin/pharmacology
- Rats
- Receptor, Serotonin, 5-HT2A/metabolism
- Receptor, Serotonin, 5-HT2A/drug effects
- Receptor, Serotonin, 5-HT1A/metabolism
- Receptor, Serotonin, 5-HT1A/drug effects
- Anorexia/metabolism
- Anorexia/drug therapy
- Cognition/drug effects
- Disease Models, Animal
- Anorexia Nervosa/drug therapy
- Anorexia Nervosa/metabolism
- Rats, Sprague-Dawley
- Body Weight/drug effects
- Reward
- Hallucinogens/pharmacology
Collapse
Affiliation(s)
- K Conn
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - L K Milton
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - K Huang
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - H Munguba
- Department of Biochemistry, Weill Cornell Medicine, New York, NY, 10065, USA
| | - J Ruuska
- University of Helsinki, Yliopistonkatu 4, 00100, Helsinki, Finland
| | - M B Lemus
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - E Greaves
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - J Homman-Ludiye
- Monash Micro Imaging, Monash University, 15 Innovation Walk, Clayton, VIC, 3800, Australia
| | - B J Oldfield
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia
| | - C J Foldi
- Monash University, Department of Physiology, 26 Innovation Walk, Clayton, VIC, 3800, Australia.
- Monash Biomedicine Discovery Institute, 23 Innovation Walk, Clayton, VIC, 3800, Australia.
| |
Collapse
|
|
6
|
Abellaneda-Pérez K, Delgado-Martínez I, Salgado P, Ginés JM, Guardiola R, Vaqué-Alcázar L, Roca-Ventura A, Molist-Puigdomènech R, Manero RM, Viles-Garcia M, Medrano-Martorell S, Bartrés-Faz D, Pascual-Leone A, Pérez-Solà V, Villalba-Martínez G. Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa. Acta Neurochir (Wien) 2024; 166:364. [PMID: 39261306 DOI: 10.1007/s00701-024-06258-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] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 08/24/2024] [Indexed: 09/13/2024]
Abstract
PURPOSE Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.
Collapse
Affiliation(s)
- Kilian Abellaneda-Pérez
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Ignacio Delgado-Martínez
- Human Anatomy and Embryology Unit, Department of Morphological Sciences, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Purificación Salgado
- Institut de Neuropsiquiatria i Addiccions (INAD), Hospital del Mar, Barcelona, Spain
| | - José María Ginés
- Institut de Neuropsiquiatria i Addiccions (INAD), Hospital del Mar, Barcelona, Spain
| | - Rocío Guardiola
- Institut de Neuropsiquiatria i Addiccions (INAD), Hospital del Mar, Barcelona, Spain
| | - Lídia Vaqué-Alcázar
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
- Sant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Alba Roca-Ventura
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
| | | | | | | | | | - David Bartrés-Faz
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
- Institut de Recerca Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Alvaro Pascual-Leone
- Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA
- Department of Neurology, Harvard Medical School, Boston, MA, USA
| | - Víctor Pérez-Solà
- Institut de Neuropsiquiatria i Addiccions (INAD), Hospital del Mar, Barcelona, Spain
- Grupo de Investigación en Salud Mental del Hospital del Mar Research Institute, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Gloria Villalba-Martínez
- Department of Neurosurgery, Hospital del Mar, Barcelona, Spain.
- Systems Neurologic and Neurotherapeutic Group at Research Institute Hospital del Mar, Barcelona, Spain.
- Universitat Pompeu Fabra, Barcelona, Spain.
| |
Collapse
|
|
7
|
Almaghrbi H, Bawadi H. Genetic polymorphisms and their association with neurobiological and psychological factors in anorexia nervosa: a systematic review. Front Psychol 2024; 15:1386233. [PMID: 38979077 PMCID: PMC11229080 DOI: 10.3389/fpsyg.2024.1386233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/29/2024] [Indexed: 07/10/2024] Open
Abstract
Background and aims Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN. Methods A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines. Results The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT, DRD2, DRD3, and DAT1, regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN. Conclusion There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder.Systematic review registration: [https://clinicaltrials.gov/], identifier [CRD42023452548].
Collapse
Affiliation(s)
- Heba Almaghrbi
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Hiba Bawadi
- Department of Human Nutrition, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| |
Collapse
|
|
8
|
Fujioka Y, Kawai K, Endo K, Ishibashi M, Iwade N, Tuerde D, Kaibuchi K, Yamashita T, Yamanaka A, Katsuno M, Watanabe H, Sobue G, Ishigaki S. Stress-impaired reward pathway promotes distinct feeding behavior patterns. Front Neurosci 2024; 18:1349366. [PMID: 38784098 PMCID: PMC11111882 DOI: 10.3389/fnins.2024.1349366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 04/18/2024] [Indexed: 05/25/2024] Open
Abstract
Although dietary behaviors are affected by neuropsychiatric disorders, various environmental conditions can have strong effects as well. We found that mice under multiple stresses, including social isolation, intermittent high-fat diet, and physical restraint, developed feeding behavior patterns characterized by a deviated bait approach (fixated feeding). All the tested stressors affected dopamine release at the nucleus accumbens (NAcc) shell and dopamine normalization reversed the feeding defects. Moreover, inhibition of dopaminergic activity in the ventral tegmental area that projects into the NAcc shell caused similar feeding pattern aberrations. Given that the deviations were not consistently accompanied by changes in the amount consumed or metabolic factors, the alterations in feeding behaviors likely reflect perturbations to a critical stress-associated pathway in the mesolimbic dopamine system. Thus, deviations in feeding behavior patterns that reflect reward system abnormalities can be sensitive biomarkers of psychosocial and physical stress.
Collapse
Affiliation(s)
- Yusuke Fujioka
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kaori Kawai
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Japan
| | - Kuniyuki Endo
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Minaka Ishibashi
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobuyuki Iwade
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Dilina Tuerde
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kozo Kaibuchi
- Research Project for Neural and Tumor Signaling, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan
| | - Takayuki Yamashita
- Department of Physiology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Akihiro Yamanaka
- Chinese Institute for Brain Research, Beijing (CIBR), Beijing, China
| | - Masahisa Katsuno
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Japan
| | - Hirohisa Watanabe
- Department of Neurology, School of Medicine, Fujita Health University, Toyoake, Japan
| | - Gen Sobue
- Aichi Medical University, Nagakute, Japan
| | - Shinsuke Ishigaki
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan
- Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
| |
Collapse
|
|
9
|
Li YT, Huang YL, Chen JJJ, Hyland BI, Wickens JR. Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate. Eur J Neurosci 2024; 59:1567-1584. [PMID: 38314648 DOI: 10.1111/ejn.16269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 12/27/2023] [Accepted: 01/17/2024] [Indexed: 02/06/2024]
Abstract
The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.
Collapse
Affiliation(s)
- Yu-Ting Li
- Neurobiology Research Unit, Okinawa Institute of Science and Technology, Okinawa, Japan
- Taiwan Instrument Research Institute, National Applied Research Laboratories, Hsinchu, Taiwan
| | - Yi-Ling Huang
- Neurobiology Research Unit, Okinawa Institute of Science and Technology, Okinawa, Japan
| | - Jia-Jin Jason Chen
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Brian Ian Hyland
- Department of Physiology, Brain Health Research Centre, University of Otago, Dunedin, New Zealand
| | - Jeffery R Wickens
- Neurobiology Research Unit, Okinawa Institute of Science and Technology, Okinawa, Japan
| |
Collapse
|
|
10
|
Zuniga SS, Flores MR, Albu A. Role of Endogenous Opioids in the Pathophysiology of Obesity and Eating Disorders. ADVANCES IN NEUROBIOLOGY 2024; 35:329-356. [PMID: 38874731 DOI: 10.1007/978-3-031-45493-6_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
This second chapter in our trilogy reviews and critically appraises the scientific evidence for the role of endogenous opioid system (EOS) activity in the onset and progression of both obesity and eating disorders. Defining features of normative eating and maladaptive eating behaviors are discussed as a foundation. We review the scientific literature pertaining to the predisposing risk factors and pathophysiology for obesity and eating disorders. Research targeting the association between obesity, disordered eating, and psychiatric comorbidities is reviewed. We conclude by discussing the involvement of endogenous opioids in neurobiological and behavior traits, and the clinical evidence for the role of the EOS in obesity and eating disorders.
Collapse
Affiliation(s)
- Sylvana Stephano Zuniga
- Obesity and Eating Disorders Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
| | - Marcela Rodriguez Flores
- Obesity and Eating Disorders Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
| | - Adriana Albu
- 2nd Department of Internal Medicine, University of Medicine and Pharmacy, Cluj-Napoca, Romania
| |
Collapse
|
|
11
|
Jin T, Kang G, Song S, Lee H, Chen Y, Kim SE, Shin MS, Park YH, Lee JE. The effects of dietary self-monitoring intervention on anthropometric and metabolic changes via a mobile application or paper-based diary: a randomized trial. Nutr Res Pract 2023; 17:1238-1254. [PMID: 38053827 PMCID: PMC10694420 DOI: 10.4162/nrp.2023.17.6.1238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 08/05/2023] [Accepted: 09/21/2023] [Indexed: 12/07/2023] Open
Abstract
BACKGROUND/OBJECTIVES Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers. Trial Registration Clinical Research Information Service Identifier: KCT0004226.
Collapse
Affiliation(s)
- Taiyue Jin
- Division of Cancer Prevention, National Cancer Control Institute, National Cancer Center, Goyang 10408, Korea
| | - Gyumin Kang
- School of Bio-Medical Science, Korea University, Sejong 30019, Korea
| | - Sihan Song
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Heejin Lee
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Yang Chen
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Sung-Eun Kim
- Department of Food and Nutrition, Sookmyung Women’s University, Seoul 04310, Korea
| | - Mal-Soon Shin
- School of Global Sport Studies, Korea University, Sejong 30019, Korea
| | - Youngja H Park
- College of Pharmacy, Korea University, Sejong 30019, Korea
| | - Jung Eun Lee
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
- The Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea
| |
Collapse
|
|
12
|
Chmiel J, Gladka A, Leszek J. The Effect of Transcranial Direct Current Stimulation (tDCS) on Anorexia Nervosa: A Narrative Review. Nutrients 2023; 15:4455. [PMID: 37892530 PMCID: PMC10610104 DOI: 10.3390/nu15204455] [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: 09/18/2023] [Revised: 10/17/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
(1) Introduction: Anorexia nervosa (AN) is a severe, debilitating disease with high incidence and high mortality. The methods of treatment used so far are moderately effective. Evidence from neuroimaging studies helps to design modern methods of therapy. One of them is transcranial direct current stimulation (tDCS), a non-invasive brain neuromodulation technique. (2) Methods: The purpose of this narrative review is to bring together all studies investigating the use of tDCS in the treatment of AN and to evaluate its effect and efficiency. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. (3) Results: The literature search resulted in five articles. These studies provide preliminary evidence that tDCS has the potential to alter eating behaviour, body weight, and food intake. Additionally, tDCS reduced symptoms of depression. Throughout all trials, stimulation targeted the left dorsolateral prefrontal cortex (DLPFC). Although the number of studies included is limited, attempts were made to elucidate the potential mechanisms underlying tDCS action in individuals with AN. Recommendations for future tDCS research in AN were issued. (4) Conclusions: The included studies have shown that tDCS stimulation of the left DLPFC has a positive effect on AN clinical symptoms and may improve them, as measured by various assessment measures. It is important to conduct more in-depth research on the potential benefits of using tDCS for treating AN. This should entail well-designed studies incorporating advanced neuroimaging techniques, such as fMRI. The aim is to gain a better understanding of how tDCS works in AN.
Collapse
Affiliation(s)
- James Chmiel
- Institute of Neurofeedback and tDCS Poland, 70-393 Szczecin, Poland
| | - Anna Gladka
- Department and Clinic of Psychiatry, Wrocław Medical University, 54-235 Wrocław, Poland
| | - Jerzy Leszek
- Department and Clinic of Psychiatry, Wrocław Medical University, 54-235 Wrocław, Poland
| |
Collapse
|
|
13
|
Calder A, Mock S, Friedli N, Pasi P, Hasler G. Psychedelics in the treatment of eating disorders: Rationale and potential mechanisms. Eur Neuropsychopharmacol 2023; 75:1-14. [PMID: 37352816 DOI: 10.1016/j.euroneuro.2023.05.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 05/28/2023] [Indexed: 06/25/2023]
Abstract
Eating disorders are serious illnesses showing high rates of mortality and comorbidity with other mental health problems. Psychedelic-assisted therapy has recently shown potential in the treatment of several common comorbidities of eating disorders, including mood disorders, post-traumatic stress disorder, and substance use disorders. The theorized therapeutic mechanisms of psychedelic-assisted therapy suggest that it could be beneficial in the treatment of eating disorders as well. In this review, we summarize preliminary data on the efficacy of psychedelic-assisted therapy in people with anorexia nervosa, bulimia nervosa, and binge eating disorder, which include studies and case reports of psychedelic-assisted therapy with ketamine, MDMA, psilocybin, and ayahuasca. We then discuss the potential therapeutic mechanisms of psychedelic-assisted therapy in these three eating disorders, including both general therapeutic mechanisms and those which are relatively specific to eating disorders. We find preliminary evidence that psychedelic-assisted therapy may be effective in the treatment of anorexia nervosa and bulimia nervosa, with very little data available on binge eating disorder. Regarding mechanisms, psychedelic-assisted therapy may be able to improve beliefs about body image, normalize reward processing, promote cognitive flexibility, and facilitate trauma processing. Just as importantly, it appears to promote general therapeutic factors relevant to both eating disorders and many of their common comorbidities. Lastly, we discuss potential safety concerns which may be associated with these treatments and present recommendations for future research.
Collapse
Affiliation(s)
- Abigail Calder
- University Center for Psychiatric Research, University of Fribourg, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland
| | - Seline Mock
- University Center for Psychiatric Research, University of Fribourg, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland
| | - Nicole Friedli
- University Center for Psychiatric Research, University of Fribourg, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland
| | - Patrick Pasi
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Switzerland
| | - Gregor Hasler
- University Center for Psychiatric Research, University of Fribourg, Chemin du Cardinal-Journet 3, 1752 Villars-sur-Glâne, Switzerland.
| |
Collapse
|
|
14
|
Schaefer LM, Forester G, Dvorak RD, Steinglass J, Wonderlich SA. Integrating aspects of affect, reward, and cognition to develop more comprehensive models of binge-eating pathology. Int J Eat Disord 2023; 56:1502-1510. [PMID: 37084184 PMCID: PMC10681362 DOI: 10.1002/eat.23971] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/28/2023] [Accepted: 04/13/2023] [Indexed: 04/22/2023]
Abstract
Reward-related processes are an increasing focus of eating disorders research. Although evidence suggests that numerous distinct reward processes may contribute to eating pathology (e.g., reward learning and delay discounting), existing etiological models of reward dysfunction tend to focus on only a limited number of reward processes, and frequently lack specificity when identifying the individual reward processes hypothesized to contribute to dysregulated eating behavior. Moreover, existing theories have been limited in their integration of reward-related processes with other demonstrated risk and maintenance factors for eating disorders (e.g., affect and cognition), potentially contributing to underdeveloped models of eating pathology. In this article, we highlight five distinct reward processes with theorized or demonstrated relevance to eating disorders involving binge-eating, followed by a review of two well-established risk/maintenance factors for binge-eating pathology. We then introduce two novel models of binge eating onset and maintenance that integrate these factors (i.e., the Affect, Reward, Cognition models), and discuss methods for testing each of the models in future research. Ultimately, we hope that the proposed models provide a springboard for the continued evolution of more precise and comprehensive theories of reward dysfunction in the eating disorders, as well as the development of novel intervention approaches. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders are associated with abnormalities in multiple domains of reward functioning. However, models of reward dysfunction within the eating disorders have not been well-integrated with prominent models of affect and cognition. This article presents two novel models of onset and maintenance for binge-eating pathology, which attempt to integrate observed reward abnormalities with other affective and cognitive processes implicated in binge-type eating disorders.
Collapse
Affiliation(s)
- Lauren M. Schaefer
- Center for Biobehavioral Research, Sanford Research, North Dakota, USA
- Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, North Dakota, USA
| | - Glen Forester
- Center for Biobehavioral Research, Sanford Research, North Dakota, USA
| | - Robert D. Dvorak
- Center for Biobehavioral Research, Sanford Research, North Dakota, USA
- Department of Psychology, University of Central Florida, Orlando, Florida, USA
| | - Joanna Steinglass
- Department of Psychiatry, Columbia University Medical Center, New York, USA
- Department of Psychiatry, New York State Psychiatric Institute, New York, USA
| | - Stephen A. Wonderlich
- Center for Biobehavioral Research, Sanford Research, North Dakota, USA
- Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, North Dakota, USA
| |
Collapse
|
|
15
|
Vasiliu O. The complex interplay between psychosocial and biological factors in pregorexia nervosa - a rapid review. Front Psychol 2023; 14:1168696. [PMID: 37404586 PMCID: PMC10315849 DOI: 10.3389/fpsyg.2023.1168696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 05/31/2023] [Indexed: 07/06/2023] Open
Abstract
The importance of detecting eating disorders (EDs) during pregnancy cannot be overemphasized, because of the major negative effects this pathology has on both maternal and fetal health. Based on a rapid review including primary and secondary reports, PN may still be considered an elusive diagnosis entity, that partially overlaps with other EDs, either well-defined, like anorexia nervosa, or still in search of their own diagnosis criteria, like orthorexia nervosa. Neurochemical and hormonal factors, psychological and social mechanisms, along with lifestyle changes create a very complex framework for clinicians interested in defining the typical features of pregorexia nervosa (PN). The personal history of EDs is considered one of the most important risk factors for PN. The core diagnostic criteria for this entity are, so far, lack of gaining weight during pregnancy, an excessive focus on counting calories and/or intense physical exercising with a secondary decrease of interest in the fetus's health, lack of acceptance of the change in body shape during pregnancy, and pathological attention for own body image. Regarding the treatment of PN, nutritional and psychosocial interventions are recommended but no specific therapeutic strategies for this disorder have been detected in the literature. Psychotherapy is considered the main intervention for pregnant women with associated EDs and mood disorders, as the pharmacological agents could have teratogenic effects or insufficient data to support their safety in this population. In conclusion, taking into consideration the methodological limitations of a rapid review, data supporting the existence of PN were found, mainly regarding tentative diagnostic criteria, risk factors, and pathophysiological aspects. These data, corroborated with the importance of preserving optimal mental health in a vulnerable population, e.g., pregnant women, justify the need for further research focused on finding specific diagnostic criteria and targeted therapeutic approaches.
Collapse
|
|
16
|
Giunti E, Collu R, Dedoni S, Castelli MP, Fratta W, Scherma M, Fadda P. Food restriction and hyperactivity induce changes in corticolimbic brain dopamine and serotonin levels in female rats. Behav Brain Res 2023; 444:114374. [PMID: 36863461 DOI: 10.1016/j.bbr.2023.114374] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/27/2023] [Accepted: 02/27/2023] [Indexed: 03/04/2023]
Abstract
Compelling data support altered dopamine (DA) and serotonin (5-HT) signaling in anorexia nervosa (AN). However, their exact role in the etiopathogenesis of AN has yet to be elucidated. Here, we evaluated the corticolimbic brain levels of DA and 5-HT in the induction and recovery phases of the activity-based anorexia (ABA) model of AN. We exposed female rats to the ABA paradigm and measured the levels of DA, 5-HT, the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and the dopaminergic type 2 (D2) receptors density in feeding- and reward-implicated brain regions (i.e., cerebral cortex, Cx; prefrontal cortex, PFC; caudate putamen, CPu; nucleus accumbens, NAcc; amygdala, Amy; hypothalamus, Hyp; hippocampus, Hipp). DA levels were significantly increased in the Cx, PFC and NAcc, while 5-HT was significantly enhanced in the NAcc and Hipp of ABA rats. Following recovery, DA was still elevated in the NAcc, while 5-HT was increased in the Hyp of recovered ABA rats. DA and 5-HT turnover were impaired at both ABA induction and recovery. D2 receptors density was increased in the NAcc shell. These results provide further proof of the impairment of the dopaminergic and serotoninergic systems in the brain of ABA rats and support the knowledge of the involvement of these two important neurotransmitter systems in the development and progression of AN. Thus, providing new insights on the corticolimbic regions involved in the monoamine dysregulations in the ABA model of AN.
Collapse
Affiliation(s)
- Elisa Giunti
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy
| | - Roberto Collu
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy
| | - Simona Dedoni
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy
| | - M Paola Castelli
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy
| | | | - Maria Scherma
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
| | - Paola Fadda
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; CNR Institute of Neuroscience, Cagliari, National Research Council, Cagliari, Italy
| |
Collapse
|
|
17
|
Celeghin A, Palermo S, Giampaolo R, Di Fini G, Gandino G, Civilotti C. Brain Correlates of Eating Disorders in Response to Food Visual Stimuli: A Systematic Narrative Review of FMRI Studies. Brain Sci 2023; 13:465. [PMID: 36979275 PMCID: PMC10046850 DOI: 10.3390/brainsci13030465] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/28/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023] Open
Abstract
This article summarizes the results of studies in which functional magnetic resonance imaging (fMRI) was performed to investigate the neurofunctional activations involved in processing visual stimuli from food in individuals with anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). A systematic review approach based on the PRISMA guidelines was used. Three databases-Scopus, PubMed and Web of Science (WoS)-were searched for brain correlates of each eating disorder. From an original pool of 688 articles, 30 articles were included and discussed. The selected studies did not always overlap in terms of research design and observed outcomes, but it was possible to identify some regularities that characterized each eating disorder. As if there were two complementary regulatory strategies, AN seems to be associated with general hyperactivity in brain regions involved in top-down control and emotional areas, such as the amygdala, insula and hypothalamus. The insula and striatum are hyperactive in BN patients and likely involved in abnormalities of impulsivity and emotion regulation. Finally, the temporal cortex and striatum appear to be involved in the neural correlates of BED, linking this condition to use of dissociative strategies and addictive aspects. Although further studies are needed, this review shows that there are specific activation pathways. Therefore, it is necessary to pay special attention to triggers, targets and maintenance processes in order to plan effective therapeutic interventions. Clinical implications are discussed.
Collapse
Affiliation(s)
- Alessia Celeghin
- Department of Psychology, University of Turin, 10124 Turin, Italy
| | - Sara Palermo
- Department of Psychology, University of Turin, 10124 Turin, Italy
- Neuroradiology Unit, Department of Diagnostic and Technology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
| | | | - Giulia Di Fini
- Department of Psychology, University of Turin, 10124 Turin, Italy
| | | | - Cristina Civilotti
- Department of Psychology, University of Turin, 10124 Turin, Italy
- Faculty of Educational Science, Salesian University Institute (IUSTO), 10155 Turin, Italy
| |
Collapse
|
|
18
|
Finch JE, Xu Z, Girdler S, Baker JH. Network analysis of eating disorder symptoms in women in perimenopause and early postmenopause. Menopause 2023; 30:275-282. [PMID: 36728103 PMCID: PMC9974533 DOI: 10.1097/gme.0000000000002141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Eating disorders (EDs) are often stereotyped as disorders of adolescence and young adulthood; however, they can occur at any age. Prevalence of EDs at midlife are approximately 3.5% and specific symptoms at midlife can have prevalences as high as 29.3%. Studies also inconsistently suggest that EDs and related symptoms may be more prevalent in midlife aged women during perimenopause compared with midlife aged women at pre-menopause. To date few studies have examined the structure of and associations between ED symptoms in women specifically during perimenopause and early postmenopause. Thus, the purpose of the current study is to investigate the structure of ED symptoms specifically during perimenopause and early postmenopause. METHODS Participants included 36 participants (45-61 y old) in a larger clinical trial who completed the Eating Disorder Examination Questionnaire (EDE-Q) at a baseline study visit. Network analysis statistical models were used to examine the structure of and associations between ED symptoms assessed via the EDE-Q. RESULTS Shape dissatisfaction and weight dissatisfaction were the top 2 central symptoms in the network. CONCLUSIONS Results corroborate previous studies and indicate that, similar to young adult samples, dissatisfaction with body image is a core feature of ED pathology across the lifespan.
Collapse
Affiliation(s)
- Jody E. Finch
- Department of Psychology, Georgia State University, P.O. Box 5010, Atlanta, GA 30302-5010, USA
| | - Ziqian Xu
- Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, 235 E. Cameron Avenue, Chapel Hill, NC 27515, USA
| | - Susan Girdler
- Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7160, 101 Manning Drive, Chapel Hill, NC 27599-7160, USA
| | - Jessica H. Baker
- Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7160, 101 Manning Drive, Chapel Hill, NC 27599-7160, USA
| |
Collapse
|
|
19
|
Banica I, Allison G, Racine SE, Foti D, Weinberg A. All the Pringle ladies: Neural and behavioral responses to high-calorie food rewards in young adult women. Psychophysiology 2023; 60:e14188. [PMID: 36183246 DOI: 10.1111/psyp.14188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 08/01/2022] [Accepted: 08/22/2022] [Indexed: 01/25/2023]
Abstract
Reward processing is vital for learning and survival, and can be indexed using the Reward Positivity (RewP), an event-related potential (ERP) component that is larger for rewards than losses. Prior work suggests that heightened motivation to obtain reward, as well as greater reward value, is associated with an enhanced RewP. However, the extent to which internal and external factors modulate neural responses to rewards, and whether such neural responses motivate reward-seeking behavior, remains unclear. The present study investigated whether the degree to which a reward is salient to an individual's current motivational state modulates the RewP, and whether the RewP predicts motivated behaviors, in a sample of 133 women. To elicit the RewP, participants completed a forced-choice food reward guessing task. Data were also collected on food-related behaviors (i.e., type of food chosen, consumption of the food reward) and motivational salience factors (i.e., self-reported hunger, time since last meal, and subjective "liking" of food reward). Results showed that hungrier participants displayed an enhanced RewP compared to less hungry individuals. Further, self-reported snack liking interacted with RewP magnitude to predict behavior, such that when participants reported low levels of snack liking, those with a smaller RewP were more likely to consume their snacks than those with a larger RewP. Our data suggest that food-related motivational state may increase neural sensitivity to food reward in young women, and that neural markers of reward sensitivity might interact with subjective reward liking to predict real-world eating behavior.
Collapse
Affiliation(s)
- Iulia Banica
- Department of Psychology, McGill University, Montreal, Quebec, Canada
| | - Grace Allison
- Department of Psychology, McGill University, Montreal, Quebec, Canada
| | - Sarah E Racine
- Department of Psychology, McGill University, Montreal, Quebec, Canada
| | - Dan Foti
- Department of Psychological Sciences, Purdue University, West Lafayette, Indiana, USA
| | - Anna Weinberg
- Department of Psychology, McGill University, Montreal, Quebec, Canada
| |
Collapse
|
|
20
|
Yu Z, Muehleman V. Eating Disorders and Metabolic Diseases. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2446. [PMID: 36767812 PMCID: PMC9916228 DOI: 10.3390/ijerph20032446] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 06/18/2023]
Abstract
Eating disorders are complex diseases with multifactorial causes. According to the Diagnostic and Statistical Manual of Mental Disorders text version (DSM-5-TR) and the WHO International Classification of Diseases and Related Health Problems (ICD-11), the major types of eating disorders include anorexia nervosa, bulimia nervosa, and binge eating disorder. The prevalence of eating disorders is alarmingly increasing globally. Moreover, the COVID-19 pandemic has led to more development and worsening of eating disorders. Patients with eating disorders exhibit high rates of psychiatric comorbidities and medical comorbidities such as obesity, diabetes, and metabolic syndrome. This paper aims to review and discuss the comorbidities of eating disorders with those metabolic diseases. Eating disorder treatment typically includes a combination of some or all approaches such as psychotherapy, nutrition education, and medications. Early detection and intervention are important for the treatment of eating disorders.
Collapse
Affiliation(s)
- Zhiping Yu
- Department of Nutrition and Dietetics, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA
| | - Valerie Muehleman
- Department of Nutrition and Dietetics, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA
- Beaufort Jasper Hampton Comprehensive Health Services, Inc., P.O. Box 357, Ridgeland, SC 29926, USA
| |
Collapse
|
|
21
|
Kechter A, Ceasar RC, Simpson KA, Schiff SJ, Dunton GF, Bluthenthal RN, Barrington-Trimis JL. A chocolate cake or a chocolate vape? Young adults describe their relationship with food and weight in the context of nicotine vaping. Appetite 2022; 175:106075. [PMID: 35525332 DOI: 10.1016/j.appet.2022.106075] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/25/2022] [Accepted: 04/30/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Emerging research has found that some young adults report vaping nicotine to control appetite and lose weight. Yet, there is little research on how young adults use vaping to manage weight, where they learn about weight-motivated vaping, and the role that food and weight motivations play in decisions to vape. METHODS We conducted one-on-one qualitative interviews with young adults aged 18-25 years old in Los Angeles, California (N = 62) from June 2018 to June 2019, who self-reported using e-cigarettes on a weekly basis or more for at least 5 months prior to study enrollment. Interviews examined participants' thoughts, feelings, and experiences related to e-cigarette use, including their understanding of the relation of vaping with eating behaviors and weight management. We analyzed the interviews using the rigorous and accelerated data reduction (RADaR) technique. RESULTS Participants reported pairing nicotine vaping with caffeinated beverages like coffee, pop/soda, tea, and after every meal (like patterns of combustible cigarette use). Participants also reported vaping nicotine as a tool to avoid binge eating and increase concentration while studying. Reports of vaping effecting appetite and eating behaviors also emerged. Vaping nicotine to suppress appetite and/or achieve weight loss was often reported in conjunction with an eating disorder. Participants reported learning about weight-motivated vaping from peers or deducing from cigarette effects and their own experiences with nicotine. Others mentioned controlling food cravings by vaping a similar e-liquid flavor. CONCLUSION Nicotine vaping was used as a tool to control weight and suppress appetite, paralleling food- and weight-related behaviors associated with cigarette use. Findings suggest a need for targeted interventions that address the role of nicotine vaping in eating/weight-related behaviors.
Collapse
Affiliation(s)
- Afton Kechter
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Institute of Addiction Science, University of Southern California, Los Angeles, CA, USA
| | - Rachel Carmen Ceasar
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Institute of Addiction Science, University of Southern California, Los Angeles, CA, USA
| | - Kelsey A Simpson
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA
| | - Sara J Schiff
- Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA
| | - Genevieve F Dunton
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Department of Psychology, University of Southern California, Los Angeles, CA, USA
| | - Ricky N Bluthenthal
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Institute of Addiction Science, University of Southern California, Los Angeles, CA, USA
| | - Jessica L Barrington-Trimis
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA; Institute of Addiction Science, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
| |
Collapse
|
|
22
|
Breton E, Fotso Soh J, Booij L. Immunoinflammatory processes: Overlapping mechanisms between obesity and eating disorders? Neurosci Biobehav Rev 2022; 138:104688. [PMID: 35594735 DOI: 10.1016/j.neubiorev.2022.104688] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 05/01/2022] [Accepted: 05/04/2022] [Indexed: 10/18/2022]
Abstract
Obesity and eating disorders are conditions that involve eating behaviors and are sometimes comorbid. Current evidence supports alterations in immunoinflammatory processes in both obesity and eating disorders. A plausible hypothesis is that immunoinflammatory processes may be involved in the pathophysiology of obesity and eating disorders. The aim of this review is to highlight the link between obesity and eating disorders, with a particular focus on immunoinflammatory processes. First, the relation between obesity and eating disorders will be presented, followed by a brief review of the literature on their association with immunoinflammatory processes. Second, developmental factors will be discussed to clarify the link between obesity, eating disorders, and immunoinflammatory processes. Genetic and epigenetic risk factors as well as the potential roles of stress pathways and early life development will be presented. Finally, implications of these findings for future research are discussed. This review highlighted biological and developmental aspects that overlap between obesity and EDs, emphasizing the need for biopsychosocial research approaches to advance current knowledge and practice in these fields.
Collapse
Affiliation(s)
- E Breton
- Sainte-Justine Hospital Research Centre, Montreal, Canada; Department of Psychiatry and Addictology, University of Montreal, Montreal, Canada
| | - J Fotso Soh
- Sainte-Justine Hospital Research Centre, Montreal, Canada; Department of Psychology, Concordia University, Montreal, Canada
| | - L Booij
- Sainte-Justine Hospital Research Centre, Montreal, Canada; Department of Psychiatry and Addictology, University of Montreal, Montreal, Canada; Department of Psychology, Concordia University, Montreal, Canada.
| |
Collapse
|
|
23
|
Ceccarini MR, Precone V, Manara E, Paolacci S, Maltese PE, Benfatti V, Dhuli K, Donato K, Guerri G, Marceddu G, Chiurazzi P, Dalla Ragione L, Beccari T, Bertelli M. A next generation sequencing gene panel for use in the diagnosis of anorexia nervosa. Eat Weight Disord 2022; 27:1869-1880. [PMID: 34822136 DOI: 10.1007/s40519-021-01331-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/07/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The aim of this study was to increase knowledge of genes associated with anorexia nervosa (AN) and their diagnostic offer, using a next generation sequencing (NGS) panel for the identification of genetic variants. The rationale underlying this test is that we first analyze the genes associated with syndromic forms of AN, then genes that were found to carry rare variants in AN patients who had undergone segregation analysis, and finally candidate genes intervening in the same molecular pathways or identified by GWAS or in mouse models. METHODS We developed an NGS gene panel and used it to screen 68 Italian AN patients (63 females, 5 males). The panel included 162 genes. Family segregation study was conducted on available relatives of probands who reported significant genetic variants. RESULTS In our analysis, we found potentially deleterious variants in 2 genes (PDE11A and SLC25A13) associated with syndromic forms of anorexia and predicted deleterious variants in the following 12 genes: CD36, CACNA1C, DRD4, EPHX2, ESR1, GRIN2A, GRIN3B, LRP2, NPY4R, PTGS2, PTPN22 and SGPP2. Furthermore, by Sanger sequencing of the promoter region of NNAT, we confirmed the involvement of this gene in the pathogenesis of AN. Family segregation studies further strengthened the possible causative role of CACNA1C, DRD4, GRIN2A, PTGS2, SGPP2, SLC25A13 and NNAT genes in AN etiology. CONCLUSION The major finding of our study is the confirmation of the involvement of the NNAT gene in the pathogenesis of AN; furthermore, this study suggests that NGS-based testing can play an important role in the diagnostic evaluation of AN, excluding syndromic forms and increasing knowledge of the genetic etiology of AN. LEVEL OF EVIDENCE Level I, experimental study.
Collapse
Affiliation(s)
- Maria Rachele Ceccarini
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
- C.I.B., Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy.
| | | | | | | | | | - Valentina Benfatti
- Department of Eating Disorder, Palazzo Francisci Todi, USL 1 Umbria, Todi, PG, Italy
| | | | | | | | | | - Pietro Chiurazzi
- Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168, Rome, Italy
- Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UOC Genetica Medica, 00168, Roma, Italy
| | - Laura Dalla Ragione
- Department of Eating Disorder, Palazzo Francisci Todi, USL 1 Umbria, Todi, PG, Italy
- Food Science and Human Nutrition Unit, University Campus Biomedico of Rome, Rome, Italy
| | - Tommaso Beccari
- Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy
- C.I.B., Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy
| | | |
Collapse
|
|
24
|
Le N, Sayers S, Mata-Pacheco V, Wagner EJ. The PACAP Paradox: Dynamic and Surprisingly Pleiotropic Actions in the Central Regulation of Energy Homeostasis. Front Endocrinol (Lausanne) 2022; 13:877647. [PMID: 35721722 PMCID: PMC9198406 DOI: 10.3389/fendo.2022.877647] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/30/2022] [Indexed: 12/11/2022] Open
Abstract
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), a pleiotropic neuropeptide, is widely distributed throughout the body. The abundance of PACAP expression in the central and peripheral nervous systems, and years of accompanying experimental evidence, indicates that PACAP plays crucial roles in diverse biological processes ranging from autonomic regulation to neuroprotection. In addition, PACAP is also abundantly expressed in the hypothalamic areas like the ventromedial and arcuate nuclei (VMN and ARC, respectively), as well as other brain regions such as the nucleus accumbens (NAc), bed nucleus of stria terminalis (BNST), and ventral tegmental area (VTA) - suggesting that PACAP is capable of regulating energy homeostasis via both the homeostatic and hedonic energy balance circuitries. The evidence gathered over the years has increased our appreciation for its function in controlling energy balance. Therefore, this review aims to further probe how the pleiotropic actions of PACAP in regulating energy homeostasis is influenced by sex and dynamic changes in energy status. We start with a general overview of energy homeostasis, and then introduce the integral components of the homeostatic and hedonic energy balance circuitries. Next, we discuss sex differences inherent to the regulation of energy homeostasis via these two circuitries, as well as the activational effects of sex steroid hormones that bring about these intrinsic disparities between males and females. Finally, we explore the multifaceted role of PACAP in regulating homeostatic and hedonic feeding through its actions in regions like the NAc, BNST, and in particular the ARC, VMN and VTA that occur in sex- and energy status-dependent ways.
Collapse
Affiliation(s)
- Nikki Le
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States
| | - Sarah Sayers
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States
| | - Veronica Mata-Pacheco
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States
| | - Edward J. Wagner
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, United States
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States
| |
Collapse
|
|
25
|
De Salles A, Lucena L, Paranhos T, Ferragut MA, de Oliveira-Souza R, Gorgulho A. Modern neurosurgical techniques for psychiatric disorders. PROGRESS IN BRAIN RESEARCH 2022; 270:33-59. [PMID: 35396030 DOI: 10.1016/bs.pbr.2022.01.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Psychosurgery refers to an ensemble of more or less invasive techniques designed to reduce the burden caused by psychiatric diseases in patients who have failed to respond to conventional therapy. While most surgeries are designed to correct apparent anatomical abnormalities, no discrete cerebral anatomical lesion is evident in most psychiatric diseases amenable to invasive interventions. Finding the optimal surgical targets in mental illness is troublesome. In general, contemporary psychosurgical procedures can be classified into one of two primary modalities: lesioning and stimulation procedures. The first group is divided into (a) thermocoagulation and (b) stereotactic radiosurgery or recently introduced transcranial magnetic resonance-guided focused ultrasound, whereas stimulation techniques mainly include deep brain stimulation (DBS), cortical stimulation, and the vagus nerve stimulation. The most studied psychiatric diseases amenable to psychosurgical interventions are severe treatment-resistant major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, anorexia nervosa, schizophrenia, and substance use disorder. Furthermore, modern neuroimaging techniques spurred the interest of clinicians to identify cerebral regions amenable to be manipulated to control psychiatric symptoms. On this way, the concept of a multi-nodal network need to be embraced, enticing the collaboration of psychiatrists, psychologists, neurologists and neurosurgeons participating in multidisciplinary groups, conducting well-designed clinical trials.
Collapse
Affiliation(s)
- Antonio De Salles
- University of California Los Angeles (UCLA), Los Angeles, CA, United States; NeuroSapiens®, Brazil; Hospital Rede D'Or, São Luiz, SP, Brazil.
| | - Luan Lucena
- NeuroSapiens®, Brazil; Hospital Rede D'Or, São Luiz, SP, Brazil
| | - Thiago Paranhos
- Hospital Rede D'Or, São Luiz, SP, Brazil; Federal University of Rio De Janeiro (UFRJ), Rio de Janeiro, Brazil
| | | | - Ricardo de Oliveira-Souza
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Federal University of the State of Rio De Janeiro (UNIRIO), Rio de Janeiro, Brazil
| | | |
Collapse
|
|
26
|
Pérez V, Villalba-Martínez G, Elices M, Manero RM, Salgado P, Ginés JM, Guardiola R, Cedrón C, Polo M, Delgado-Martínez I, Conesa G, Medrano S, Portella MJ. Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa. EUROPEAN EATING DISORDERS REVIEW 2022; 30:353-363. [PMID: 35322504 DOI: 10.1002/erv.2895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 02/03/2022] [Accepted: 02/22/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Up to 20% of the cases of anorexia nervosa (AN) are chronic and treatment-resistant. Recently, the efficacy of deep brain stimulation (DBS) for severe cases of AN has been explored, with studies showing an improvement in body mass index and other psychiatric outcomes. While the effects of DBS on cognitive domains have been studied in patients with other neurological and psychiatric conditions so far, no evidence has been gathered in AN. METHODS Eight patients with severe, chronic, treatment-resistant AN received DBS either to the nucleus accumbens (NAcc) or subcallosal cingulate (SCC; four subjects on each target). A comprehensive battery of neuropsychological and clinical outcomes was used before and 6-month after surgery. FINDINGS Although Body Mass Index (BMI) did not normalise, statistically significant improvements in BMI, quality of life, and performance on cognitive flexibility were observed after 6 months of DBS. Changes in BMI were related to a decrease in depressive symptoms and an improvement in memory functioning. INTERPRETATION These findings, although preliminary, support the use of DBS in AN, pointing to its safety, even for cognitive functioning; improvements of cognitive flexibility are reported. DBS seems to exert changes on cognition and mood that accompany BMI increments. Further studies are needed better to determine the impact of DBS on cognitive functions.
Collapse
Affiliation(s)
- Víctor Pérez
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.,Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parce de Salut Mar, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
| | | | - Matilde Elices
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parce de Salut Mar, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
| | - Rosa María Manero
- Department of Neurology, Hospital del Mar, Barcelona, Catalonia, Spain
| | - Purificación Salgado
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - José María Ginés
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Rocío Guardiola
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Carlos Cedrón
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - María Polo
- Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | | | - Gerardo Conesa
- Department of Neurosurgery, Hospital del Mar, Barcelona, Spain
| | - Santiago Medrano
- Department of Radiology, Hospital del Mar, Barcelona, Catalonia, Spain
| | - Maria J Portella
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.,Institut de d'Investigació Biomèdica Sant Pau. Hospital de la Santa Creu i Sant Pau. UAB, Barcelona, Catalonia, Spain
| |
Collapse
|
|
27
|
Abstract
OBJECTIVE Binge eating, a core diagnostic symptom in binge eating disorder and bulimia nervosa, increases the risk of multiple physiological and psychiatric disorders. The neurotransmitter dopamine is involved in food craving, decision making, executive functioning, and impulsivity personality trait; all of which contribute to the development and maintenance of binge eating. The objective of this paper is to review the associations of dopamine levels/activities, dopamine regulator (e.g., dopamine transporter, degrading enzymes) levels/activities, and dopamine receptor availability/affinity with binge eating. METHODS A literature search was conducted in PubMed and PsycINFO to obtain human and animal studies published since 2010. RESULTS A total of 31 studies (25 human, six animal) were included. Among the human studies, there were 12 case-control studies, eight randomized controlled trials, and five cross-sectional studies. Studies used neuroimaging (e.g., positron emission tomography), genetic, and pharmacological (e.g., dopamine transporter inhibitor) techniques to describe or compare dopamine levels/activities, dopamine transporter levels/activities, dopamine degrading enzyme (e.g., catechol-O-methyltransferase) levels/activities, and dopamine receptor (e.g., D1, D2) availability/affinity among participants with and without binge eating. Most human and animal studies supported an altered dopaminergic state in binge eating (26/31, 83.9%); however, results were divergent regarding whether the altered state was hyperdopaminergic (9/26, 34.6%) or hypodopaminergic (17/26, 65.4%). The mixed findings may be partially explained by the variability in sample characteristics, study design, diagnosis criteria, and neuroimaging/genetic/pharmacological techniques used. However, it is possible that instead of being mutually exclusive, the hyperdopaminergic and hypodopaminergic state may co-exist, but in different stages of binge eating or in different individual genotypes. CONCLUSIONS For future studies to clarify the inconsistent findings, a homogenous sample that controls for confounders that may influence dopamine levels (e.g., psychiatric diseases) is preferable. Longitudinal studies are needed to evaluate whether the hyper- and hypo-dopaminergic states co-exist in different stages of binge eating or co-exist in individual phenotypes. Binge eating is characterized by eating a large amount of food in a short time and a feeling of difficulty to stop while eating. Binge eating is the defining symptom of binge eating disorder and bulimia nervosa, both of which are associated with serious health consequences. Studies have identified several psychological risk factors of binge eating, including a strong desire for food, impaired cognitive skills, and distinct personality traits (e.g., quick action without careful thinking). However, the physiological markers of binge eating remain unclear. Dopamine is a neurotransmitter that is heavily involved in feeding behavior, human motivation, cognitive ability, and personality. Therefore, dopamine is believed to play a critical role in binge eating. This review synthesized study findings related to the levels and activities of dopamine, dopamine regulators, and dopamine receptors in the context of binge eating. The primary finding is that most studies that used neuroimaging, genetic, or drug techniques found an altered dopaminergic state related to binge eating. However, the literature is inconsistent concerning the direction of the alteration. Considering the mixed findings and the limitations in study design, future studies, especially those that include repeated measurements, are needed to clarify the role of dopamine in binge eating.
Collapse
Affiliation(s)
- Yang Yu
- School of Nursing, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642 USA
| | - Renee Miller
- Brain and Cognitive Sciences, University of Rochester, 303F Meliora Hall, Rochester, NY 14627 USA
| | - Susan W. Groth
- School of Nursing, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642 USA
| |
Collapse
|
|
28
|
Acute gastric perforation after leaving against medical advice: A case presentation. Trauma Case Rep 2022; 37:100598. [PMID: 35024408 PMCID: PMC8724944 DOI: 10.1016/j.tcr.2021.100598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2021] [Indexed: 11/24/2022] Open
Abstract
Introduction Gastric perforation with necrosis is rare following acute gastric dilation (AGD) and can be fatal. We present a case of a patient with AGD due to a binge-eating episode who left the emergency department (ED) against medical advice (AMA) only to return with gastric perforation and necrosis requiring total splenectomy and partial gastrectomy. Case A 28-year-old female without a remarkable past medical history presented to the ED with diffuse abdominal pain and obstipation after a three-day “food crawl.” On admission, a computerized tomography (CT) scan revealed a markedly dilated stomach from the diaphragm to the pelvis with severe mass effect. The therapeutic plan at the time was gastric decompression via a nasogastric tube. The following day, the patient reported feeling better and left AMA only to return the same evening with worsening symptoms and peritoneal signs. The patient was then emergently taken to the operating room (OR). In the OR, laparotomy revealed frank spillage of partially digested food and necrosis along the greater curvature of the stomach that extended to the spleen. Damage control surgery was performed, which required a total splenectomy and a partial gastrectomy. The patient was admitted to the intensive care unit (ICU) and subsequently underwent five more trips to the OR due to severe edema that delayed the primary closure of the fascia. Once the patient was transferred out of the ICU, she was evaluated by psychiatry and diagnosed with a binge-eating disorder. Conclusion This case demonstrates the severity of acute gastric dilation and its potentially lethal consequences. In some cases, such as this one, the patient may present with mild symptoms and not comprehend the gravity of the situation. Therefore, it is important for clinicians to recognize this condition as a true emergency and perform immediate decompression and evaluation for surgery.
Collapse
|
|
29
|
Le N, Hernandez J, Gastelum C, Perez L, Vahrson I, Sayers S, Wagner EJ. Pituitary Adenylate Cyclase Activating Polypeptide Inhibits A 10 Dopamine Neurons and Suppresses the Binge-like Consumption of Palatable Food. Neuroscience 2021; 478:49-64. [PMID: 34597709 DOI: 10.1016/j.neuroscience.2021.09.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 10/20/2022]
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) binds to PACAP-specific (PAC1) receptors in multiple hypothalamic areas, especially those regulating energy balance. PACAP neurons in the ventromedial nucleus (VMN) exert anorexigenic effects within the homeostatic energy balance circuitry. Since PACAP can also reduce the consumption of palatable food, we tested the hypothesis that VMN PACAP neurons project to the ventral tegmental area (VTA) to inhibit A10 dopamine neurons via PAC1 receptors and KATP channels, and thereby suppress binge-like consumption. We performed electrophysiological recordings in mesencephalic slices from male PACAP-Cre and tyrosine hydroxylase (TH)-Cre mice. Initially, we injected PACAP (30 pmol) into the VTA, where it suppressed binge intake in wildtype male but not female mice. Subsequent tract tracing studies uncovered projections of VMN PACAP neurons to the VTA. Optogenetic stimulation of VMN PACAP neurons in voltage clamp induced an outward current and increase in conductance in VTA neurons, and a hyperpolarization and decrease in firing in current clamp. These effects were markedly attenuated by the KATP channel blocker tolbutamide (100 μM) and PAC1 receptor antagonist PACAP6-38 (200 nM). In recordings from A10 dopamine neurons in TH-Cre mice, we replicated the outward current by perfusing PACAP1-38 (100 nM). This response was again completely blocked by tolbutamide and PACAP6-38, and associated with a hyperpolarization and decrease in firing. These findings demonstrate that PACAP activates PAC1 receptors and KATP channels to inhibit A10 dopamine neurons and sex-dependently suppress binge-like consumption. Accordingly, they advance our understanding of how PACAP regulates energy homeostasis via the hedonic energy balance circuitry.
Collapse
Affiliation(s)
- Nikki Le
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Jennifer Hernandez
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Cassandra Gastelum
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Lynnea Perez
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Isabella Vahrson
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Sarah Sayers
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Edward J Wagner
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA; College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA.
| |
Collapse
|
|
30
|
Elkfury JL, Antunes LC, Dal Moro Angoleri L, Sipmann RB, de Souza A, da Silva Torres IL, Caumo W. Dysfunctional eating behavior in fibromyalgia and its association with serum biomarkers of brain plasticity (BDNF and S100B): an exploratory study. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2021; 65:713-722. [PMID: 34591410 PMCID: PMC10065384 DOI: 10.20945/2359-3997000000406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 04/19/2021] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To assess disordered eating, hunger and satiety perceptions in women with fibromyalgia (FM) compared to healthy controls (HC) and their association with biomarkers of brain plasticity (brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B)). METHODS Cross-sectional exploratory study. The sample included FM (n = 20) and HC (n = 19), matched to age and waist perimeter. Dysfunctional eating was assessed through the Three Factor Eating Questionnaire and Eating Disorders Examination with a questionnaire. Hunger and satiety levels were rated by a Numerical Scale. Serum leptin, S100B and BDNF were analyzed. RESULTS The MANCOVA analysis showed that the mean of Emotional Eating rates was 30.65% higher in FM compared to HC (p = 0.015). Eating, shape and weight concerns were 77.77%, 57.14% and 52.22% higher in FM (p = <0.001) compared to HC, respectively. Moreover, the FM group reported higher scores for feeling of hunger "[5.2 (±2.9) vs. 4.8 (±2.0); p = 0.042] and lower scores for satiety [7.0 (±1.7) vs. 8.3 (±1.0); p = 0.038]. In the FM group, serum BDNF was negatively associated with hunger (r = - 0.52; p = 0.02), while S100B was positively associated with hunger scores (r = 0.463; p = 0.004). CONCLUSION The present findings support the hypothesis that the association between FM and obesity can be mediated by a hedonistic pathway. Further research is needed.
Collapse
Affiliation(s)
- Jéssica Lorenzzi Elkfury
- Programa de Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Luciana C Antunes
- Programa de Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Centro de Ciências da Saúde, Divisão de Nutrição, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil
| | - Letícia Dal Moro Angoleri
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Laboratório de Dor e Neuromodulação, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Raquel Busanello Sipmann
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Laboratório de Dor e Neuromodulação, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Andressa de Souza
- Programa de Pós-graduação em Saúde e Desenvolvimento Humano, LaSalle, Canoas, RS, Brasil
- Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Iraci Lucena da Silva Torres
- Laboratório de Dor e Neuromodulação, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
| | - Wolnei Caumo
- Programa de Pós-graduação em Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Laboratório de Dor e Neuromodulação, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil
- Departamento de Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil,
| |
Collapse
|
|
31
|
Blanco-Gandia MC, Montagud-Romero S, Rodríguez-Arias M. Binge eating and psychostimulant addiction. World J Psychiatry 2021; 11:517-529. [PMID: 34631457 PMCID: PMC8475000 DOI: 10.5498/wjp.v11.i9.517] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/13/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Many of the various factors, characteristics, and variables involved in the addictive process can determine an individual’s vulnerability to develop drug addiction. Hedonic eating, based on pleasure rather than energy needs, modulates the same reward circuits, as do drugs of abuse. According to the last report of the World Health Organization, the worldwide obesity rate has more than doubled since 1980, reaching especially critical levels in children and young people, who are overexposed to high-fat, high-sugar, energy-dense foods. Over the past few decades, there has been an increase in the number of studies focused on how eating disorders can lead to the development of drug addiction and on the comorbidity that exists between the two disorders. Herein, we review the most recent research on the subject, focusing especially on animal models of binge eating disorders and drug addiction. The complex profile of patients with substance use and binge eating disorders requires an integrated response to dually diagnosed patients. Nutritional patterns should be considered an important variable in the treatment of substance use disorders, and future studies need to focus on specific treatments and interventions in individuals who show a special vulnerability to shift from one addiction to the other.
Collapse
Affiliation(s)
| | | | - Marta Rodríguez-Arias
- Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia 46010, Spain
| |
Collapse
|
|
32
|
Reed CH, Bauer EE, Shoeman A, Buhr TJ, Clark PJ. Acute Stress Exposure Alters Food-Related Brain Monoaminergic Profiles in a Rat Model of Anorexia. J Nutr 2021; 151:3617-3627. [PMID: 34522956 PMCID: PMC8643607 DOI: 10.1093/jn/nxab298] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/02/2021] [Accepted: 08/12/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Adverse life experiences are a major risk factor for anorexia nervosa (AN). Eating-provoked anxiousness associated with AN is postulated to be due to food-related exaggerated serotonin activity in the brain and imbalances of monoamine neurotransmitters. OBJECTIVES Using a rodent model of stress-induced hypophagia, we investigated if stress exposure augments food-related serotonin turnover and imbalances in measures of brain serotonin and dopamine activity in manners consistent with anxiousness toward food and restricted eating. METHODS Adult male F344 rats were conditioned to associate an audio cue with daily food over 2 weeks, after which half of the rats were exposed to a single episode of tail shocks (stress) or left undisturbed (nonstressed). All rats were killed 48 h later, during a control period, the food-associated cue, or a period of food access. Serotonin, dopamine, and norepinephrine, as well as metabolite concentrations, were assessed across brain regions comprising reward, emotion, and feeding circuits relevant to AN in acutely stressed and nonstressed rats using HPLC. Statistical significance level was 5%. RESULTS Stress-induced rat hypophagia paralleled an augmented serotonin turnover in response to the food-associated cue in the hypothalamus and hippocampus, as well as food access in the hypothalamus and cortical areas (all P < 0.05). Stress exposure increased the ratio of serotonin to dopamine metabolites across several brain areas, but the magnitude of this imbalance was further augmented during the food-associated cue and food access in the brainstem, hippocampus, and cortical areas (all P < 0.05). Finally, stress lowered norepinephrine concentrations by 18% in the hypothalamus (P < 0.05). CONCLUSIONS The observed stress-induced changes to monoamine profiles in rats could have key implications for physiological states that contribute to restricted eating and may hold relevance for the development of AN precipitated by adverse life experiences.
Collapse
Affiliation(s)
- Carter H Reed
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA,Department of Kinesiology, Iowa State University, Ames, IA, USA
| | - Ella E Bauer
- Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA,Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA,Neuroscience Program, Iowa State University, Ames, IA, USA
| | - Allyse Shoeman
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA
| | - Trevor J Buhr
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA,Neuroscience Program, Iowa State University, Ames, IA, USA
| | | |
Collapse
|
|
33
|
Skowron K, Kurnik-Łucka M, Jurczyk M, Aleksandrovych V, Stach P, Dadański E, Kuśnierz-Cabala B, Jasiński K, Węglarz WP, Mazur P, Podlasz P, Wąsowicz K, Gil K. Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa? Nutrients 2021; 13:2876. [PMID: 34445036 PMCID: PMC8399373 DOI: 10.3390/nu13082876] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 08/16/2021] [Accepted: 08/19/2021] [Indexed: 12/24/2022] Open
Abstract
Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.
Collapse
Affiliation(s)
- Kamil Skowron
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Magdalena Kurnik-Łucka
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Michał Jurczyk
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Veronika Aleksandrovych
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Paulina Stach
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Emil Dadański
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| | - Beata Kuśnierz-Cabala
- Department of Diagnostics, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Krakow, Poland;
| | - Krzysztof Jasiński
- Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland; (K.J.); (W.P.W.)
| | - Władysław P. Węglarz
- Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland; (K.J.); (W.P.W.)
| | - Paulina Mazur
- Department of Medical Diagnostics, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland;
| | - Piotr Podlasz
- Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (P.P.); (K.W.)
| | - Krzysztof Wąsowicz
- Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (P.P.); (K.W.)
| | - Krzysztof Gil
- Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Krakow, Poland; (M.K.-Ł.); (M.J.); (V.A.); (P.S.); (E.D.); (K.G.)
| |
Collapse
|
|
34
|
Gastelum C, Perez L, Hernandez J, Le N, Vahrson I, Sayers S, Wagner EJ. Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status. Int J Mol Sci 2021; 22:2728. [PMID: 33800452 PMCID: PMC7962960 DOI: 10.3390/ijms22052728] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/03/2021] [Accepted: 03/04/2021] [Indexed: 12/15/2022] Open
Abstract
Energy homeostasis is regulated in coordinate fashion by the brain-gut axis, the homeostatic energy balance circuitry in the hypothalamus and the hedonic energy balance circuitry comprising the mesolimbcortical A10 dopamine pathway. Collectively, these systems convey and integrate information regarding nutrient status and the rewarding properties of ingested food, and formulate it into a behavioral response that attempts to balance fluctuations in consumption and food-seeking behavior. In this review we start with a functional overview of the homeostatic and hedonic energy balance circuitries; identifying the salient neural, hormonal and humoral components involved. We then delve into how the function of these circuits differs in males and females. Finally, we turn our attention to the ever-emerging roles of nociceptin/orphanin FQ (N/OFQ) and pituitary adenylate cyclase-activating polypeptide (PACAP)-two neuropeptides that have garnered increased recognition for their regulatory impact in energy homeostasis-to further probe how the imposed regulation of energy balance circuitry by these peptides is affected by sex and altered under positive (e.g., obesity) and negative (e.g., fasting) energy balance states. It is hoped that this work will impart a newfound appreciation for the intricate regulatory processes that govern energy homeostasis, as well as how recent insights into the N/OFQ and PACAP systems can be leveraged in the treatment of conditions ranging from obesity to anorexia.
Collapse
Affiliation(s)
- Cassandra Gastelum
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Lynnea Perez
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Jennifer Hernandez
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Nikki Le
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Isabella Vahrson
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Sarah Sayers
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
| | - Edward J. Wagner
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA; (C.G.); (L.P.); (J.H.); (N.L.); (I.V.); (S.S.)
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
| |
Collapse
|
|
35
|
Heidinger BA, Cameron JD, Vaillancourt R, De Lisio M, Ngu M, Tasca GA, Chyurlia L, Doucet É, Doucette S, Maria Obregón Rivas A, Goldfield GS. No association between dopaminergic polymorphisms and response to treatment of binge-eating disorder. Gene 2021; 781:145538. [PMID: 33631245 DOI: 10.1016/j.gene.2021.145538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 02/16/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND The genetics of binge-eating disorder (BED) is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined if DA genes influence response to behavioral treatment of BED. OBJECTIVE The primary objective of this study was to examine the ability of DA-associated polymorphisms to predict BED treatment response measured using binge frequency over 12 months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity. METHODS Women aged 18-64 years old were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these 4 polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination - Interview) and body composition (Tanita BC-418) were assessed in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was conducted on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n = 72), obesity without BED (n = 27), and normal-weight without BED (n = 45). RESULTS There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics. CONCLUSIONS Our study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. Future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as examine their impact on both behavioral and pharmacological-based treatment for BED.
Collapse
Affiliation(s)
- Brandon A Heidinger
- Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - Jameason D Cameron
- Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - Regis Vaillancourt
- Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - Michael De Lisio
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, Canada
| | - Matthew Ngu
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Giorgio A Tasca
- School of Psychology, University of Ottawa, Ottawa, ON, Canada
| | - Livia Chyurlia
- School of Psychology, University of Ottawa, Ottawa, ON, Canada
| | - Éric Doucet
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Steve Doucette
- Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada
| | - Ana Maria Obregón Rivas
- Escuela de Nutrición y dietética, Facultad de Ciencias para el cuidado de la Salud, Universidad San Sebastián, Concepción, Chile
| | - Gary S Goldfield
- Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
| |
Collapse
|
|
36
|
Ma R, Mikhail ME, Culbert KM, Johnson AW, Sisk CL, Klump KL. Ovarian Hormones and Reward Processes in Palatable Food Intake and Binge Eating. Physiology (Bethesda) 2021; 35:69-78. [PMID: 31799907 DOI: 10.1152/physiol.00013.2019] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contribute to these relationships, but additional studies are needed to confirm and extend findings.
Collapse
Affiliation(s)
- Ruofan Ma
- Department of Psychology, Michigan State University, East Lansing, Michigan
| | - Megan E Mikhail
- Department of Psychology, Michigan State University, East Lansing, Michigan
| | - Kristen M Culbert
- Department of Psychology, University of Nevada-Las Vegas, Las Vegas, Nevada
| | - Alex W Johnson
- Neuroscience Program, Michigan State University, East Lansing, Michigan
| | - Cheryl L Sisk
- Neuroscience Program, Michigan State University, East Lansing, Michigan
| | - Kelly L Klump
- Department of Psychology, Michigan State University, East Lansing, Michigan
| |
Collapse
|
|
37
|
Hernandez J, Perez L, Soto R, Le N, Gastelum C, Wagner EJ. Nociceptin/orphanin FQ neurons in the Arcuate Nucleus and Ventral Tegmental Area Act via Nociceptin Opioid Peptide Receptor Signaling to Inhibit Proopiomelanocortin and A 10 Dopamine Neurons and Thereby Modulate Ingestion of Palatable Food. Physiol Behav 2021; 228:113183. [PMID: 32979341 PMCID: PMC7736116 DOI: 10.1016/j.physbeh.2020.113183] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 09/18/2020] [Accepted: 09/21/2020] [Indexed: 12/13/2022]
Abstract
The neuropeptide nociceptin/orphanin FQ (N/OFQ) inhibits neuronal activity via its cognate nociceptin opioid peptide (NOP) receptor throughout the peripheral and central nervous systems, including those areas involved in the homeostatic and hedonic regulation of energy homeostasis. We thus tested the hypothesis that N/OFQ neurons in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA) act via NOP receptor signaling to inhibit nearby anorexigenic proopiomelanocortin (POMC) and A10 dopamine neuronal excitability, respectively, and thereby modulate ingestion of palatable food. Electrophysiologic recordings were performed in slices prepared from transgenic male and ovariectomized (OVX) female N/OFQ-cre/enhanced green fluorescent protein-POMC, N/OFQ-cre and tyrosine hydroxylase-cre animals to see if optogenetically-stimulated peptide release from N/OFQ neurons could directly inhibit these neuronal populations. Binge-feeding behavioral experiments were also conducted where animals were exposed to a high-fat-diet (HFD) for one hour each day for five days and monitored for energy intake. Photostimulation of ARC and VTA N/OFQ neurons produces an outward current in POMC and A10 dopamine neurons receiving input from these cells. This is associated with a hyperpolarization and decreased firing. These features are also sex hormone- and diet-dependent; with estradiol-treated slices from OVX females being less sensitive, and obese males being more sensitive, to N/OFQ. Limited access to HFD causes a dramatic escalation in consumption, such that animals eat 25-45% of their daily intake during that one-hour exposure. Moreover, the NOP receptor-mediated regulation of these energy balance circuits are engaged, as N/OFQ injected directly into the VTA or ARC respectively diminishes or potentiates this binge-like increase in a manner heightened by diet-induced obesity or dampened by estradiol in females. Collectively, these findings provide key support for the idea that N/OFQ regulates appetitive behavior in sex-, site- and diet-specific ways, along with important insights into aberrant patterns of feeding behavior pertinent to the pathogenesis of food addiction.
Collapse
Affiliation(s)
- Jennifer Hernandez
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
| | - Lynnea Perez
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Rosy Soto
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
| | - Nikki Le
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Cassandra Gastelum
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Edward J Wagner
- Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA; College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA.
| |
Collapse
|
|
38
|
Hildebrandt BA, Ahmari SE. Breaking It Down: Investigation of Binge Eating Components in Animal Models to Enhance Translation. Front Psychiatry 2021; 12:728535. [PMID: 34484010 PMCID: PMC8414642 DOI: 10.3389/fpsyt.2021.728535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 07/19/2021] [Indexed: 12/28/2022] Open
Abstract
Binge eating (BE) is a core eating disorder behavior that is present across nearly all eating disorder diagnoses (e. g., bulimia nervosa, binge eating disorder, anorexia nervosa binge/purge subtype), and is also widely present in the general population. Despite the prevalence of BE, limited treatment options exist and there are often high rates of relapse after treatment. There is evidence showing that genetic factors contribute to the heritability of BE and support for biological contributions to BE. However, more work is needed to fully understand neurobiological mechanisms underlying BE. One approach to target this problem is to separate BE into its distinct clinical components that can be more easily modeled using pre-clinical approaches. To date, a variety of animal models for BE have been used in pre-clinical studies; but there have been challenges translating this work to human BE. Here, we review these pre-clinical approaches by breaking them down into three clinically-significant component parts (1) consumption of a large amount of food; (2) food consumption within a short period of time; and (3) loss of control over eating. We propose that this rubric identifies the most frequently used and effective ways to model components of BE behavior using pre-clinical approaches with the strongest clinical relevance. Finally, we discuss how current pre-clinical models have been integrated with techniques using targeted neurobiological approaches and propose ways to improve translation of pre-clinical work to human investigations of BE that could enhance our understanding of BE behavior.
Collapse
Affiliation(s)
- Britny A Hildebrandt
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Susanne E Ahmari
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.,Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United States.,Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, United States
| |
Collapse
|
|
39
|
Walsh K, Iskandar G, Kamboj SK, Das RK. An assessment of rapamycin for weakening binge-eating memories via reconsolidation: a pre-registered, double-blind randomised placebo-controlled experimental study. Psychol Med 2021; 51:158-167. [PMID: 31736460 DOI: 10.1017/s003329171900312x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation. METHODS Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up. RESULTS Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices. CONCLUSIONS We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.
Collapse
Affiliation(s)
- Katie Walsh
- Clinical, Educational and Health Psychology, University College London, Gower Street, London, WC1E 6BT
| | - Georges Iskandar
- University College Hospital and University College Hospital at Westmoreland Street, London, UK
| | - Sunjeev K Kamboj
- Clinical, Educational and Health Psychology, University College London, Gower Street, London, WC1E 6BT
| | - Ravi K Das
- Clinical, Educational and Health Psychology, University College London, Gower Street, London, WC1E 6BT
| |
Collapse
|
|
40
|
Qadiri Q, York H, Muth BJ, Longoria CR, Campbell SC, Guers JJ. "The addition of naltrexone alters cerebral glucose uptake following acute forced swimming". Physiol Behav 2021; 228:113199. [PMID: 33038350 DOI: 10.1016/j.physbeh.2020.113199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 09/23/2020] [Accepted: 10/05/2020] [Indexed: 11/29/2022]
Abstract
Endogenous opioid release has been linked to exercise. We investigated if opioid blockade following forced swimming, a common model of rodent exercise, influenced cerebral glucose metabolism in mice. PET scan was used to assess the uptake of Fludeoxyglucose (FDG-18), a marker of cerebral glucose metabolism in 19 regions of the interest in the brain following: forced swimming, an acute dose of the opioid receptor blocker naltrexone or a combination of both. Forced swimming increased glucose uptake in the cerebellum, while naltrexone + forced swimming increased glucose uptake in the hypothalamus, forebrain, septum and amygdala. This suggests that opioid blockade alters the typical pattern of cerebral glucose uptake following forced swimming in mice in certain areas of the brain.
Collapse
Affiliation(s)
| | - Harlee York
- Exercise Science Program, Stockton University, Galloway, NJ 08205
| | - Bryce J Muth
- Exercise Science Program, Stockton University, Galloway, NJ 08205
| | - Candace R Longoria
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901
| | - Sara C Campbell
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901
| | - John J Guers
- Department of Biology, Behavioral Neuroscience and Health Science, Rider University, Lawrenceville, NJ 08646.
| |
Collapse
|
|
41
|
Liu T, Pan X, Wang X, Feenstra KA, Heringa J, Huang Z. Predicting the relationships between gut microbiota and mental disorders with knowledge graphs. Health Inf Sci Syst 2020; 9:3. [PMID: 33262885 PMCID: PMC7686388 DOI: 10.1007/s13755-020-00128-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 09/30/2020] [Indexed: 01/14/2023] Open
Abstract
Gut microbiota produce and modulate the production of neurotransmitters which have been implicated in mental disorders. Neurotransmitters may act as ‘matchmaker’ between gut microbiota imbalance and mental disorders. Most of the relevant research effort goes into the relationship between gut microbiota and neurotransmitters and the other between neurotransmitters and mental disorders, while few studies collect and analyze the dispersed research results in systematic ways. We therefore gather the dispersed results that in the existing studies into a structured knowledge base for identifying and predicting the potential relationships between gut microbiota and mental disorders. In this study, we propose to construct a gut microbiota knowledge graph for mental disorder, which named as MiKG4MD. It is extendable by linking to future ontologies by just adding new relationships between existing information and new entities. This extendibility is emphasized for the integration with existing popular ontologies/terminologies, e.g. UMLS, MeSH, and KEGG. We demonstrate the performance of MiKG4MD with three SPARQL query test cases. Results show that the MiKG4MD knowledge graph is an effective method to predict the relationships between gut microbiota and mental disorders.
Collapse
Affiliation(s)
- Ting Liu
- Knowledge Representation and Reasoning (KR&R) Group, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Center for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Xueli Pan
- Knowledge Representation and Reasoning (KR&R) Group, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Xu Wang
- Knowledge Representation and Reasoning (KR&R) Group, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - K Anton Feenstra
- Center for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jaap Heringa
- Center for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Zhisheng Huang
- Knowledge Representation and Reasoning (KR&R) Group, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Brain Protection Innovation Center, Capital Medical University, Beijing, China
| |
Collapse
|
|
42
|
Schaumberg K, Reilly EE, Gorrell S, Levinson CA, Farrell NR, Brown TA, Smith KM, Schaefer LM, Essayli JH, Haynos AF, Anderson LM. Conceptualizing eating disorder psychopathology using an anxiety disorders framework: Evidence and implications for exposure-based clinical research. Clin Psychol Rev 2020; 83:101952. [PMID: 33221621 DOI: 10.1016/j.cpr.2020.101952] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 11/09/2020] [Accepted: 11/09/2020] [Indexed: 12/13/2022]
Abstract
Eating disorders (EDs) and anxiety disorders (ADs) evidence shared risk and significant comorbidity. Recent advances in understanding of anxiety-based disorders may have direct application to research and treatment efforts for EDs. The current review presents an up-to-date, behavioral conceptualization of the overlap between anxiety-based disorders and EDs. We identify ways in which anxiety presents in EDs, consider differences between EDs and ADs relevant to treatment adaptions, discuss how exposure-based strategies may be adapted for use in ED treatment, and outline directions for future mechanistic, translational, and clinical ED research from this perspective. Important research directions include: simultaneous examination of the extent to which EDs are characterized by aberrant avoidance-, reward-, and/or habit-based neurobiological and behavioral processes; improvement in understanding of how nutritional status interacts with neurobiological characteristics of EDs; incorporation of a growing knowledge of biobehavioral signatures in ED treatment planning; development of more comprehensive exposure-based treatment approaches for EDs; testing whether certain exposure interventions for AD are appropriate for EDs; and improvement in clinician self-efficacy and ability to use exposure therapy for EDs.
Collapse
Affiliation(s)
| | | | - Sasha Gorrell
- University of California, San Francisco, United States of America
| | - Cheri A Levinson
- University of Louisville, Department of Psychological & Brain Sciences, United States of America
| | | | - Tiffany A Brown
- University of California, San Diego, United States of America
| | - Kathryn M Smith
- Sanford Health, United States of America; University of Southern California, United States of America
| | | | | | - Ann F Haynos
- University of Minnesota, United States of America
| | | |
Collapse
|
|
43
|
Neurochemical regulators of food behavior for pharmacological treatment of obesity: current status and future prospects. Future Med Chem 2020; 12:1865-1884. [PMID: 33040605 DOI: 10.4155/fmc-2019-0361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
In recent decades, obesity has become a pandemic disease and appears to be an ultimate medical and social problem. Existing antiobesity drugs show low efficiency and a wide variety of side effects. In this review, we discuss possible mechanisms underlying brain-gut-adipose tissue axis, as well as molecular biochemical characteristics of various neurochemical regulators of body weight and appetite. Multiple brain regions are responsible for eating behavior, hedonic eating and food addiction. The existing pharmacological targets for treatment of obesity were reviewed as well.
Collapse
|
|
44
|
Crucianelli L, Demartini B, Goeta D, Nisticò V, Saramandi A, Bertelli S, Todisco P, Gambini O, Fotopoulou A. The Anticipation and Perception of Affective Touch in Women with and Recovered from Anorexia Nervosa. Neuroscience 2020; 464:143-155. [PMID: 32937191 DOI: 10.1016/j.neuroscience.2020.09.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 09/01/2020] [Accepted: 09/02/2020] [Indexed: 11/19/2022]
Abstract
Disruptions in reward processing and anhedonia have long been observed in Anorexia Nervosa (AN). Interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialised, interoceptive C-tactile system originating at the periphery, or a more top-down mechanism in the processing of tactile pleasantness remains debated. Here, we investigated differences between patients with and recovered from AN (RAN) and healthy controls (HC) in the perception of pleasantness of touch delivered in a CT-optimal versus a CT-non-optimal manner, and in their top-down, anticipatory beliefs about the perceived pleasantness of touch. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic touch applied to the forearm of 27 women with AN, 24 women who have recovered and 30 HCs using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than HCs, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in the perception of CT-optimal touch were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, tactile anhedonia in AN might persist as a trait even after otherwise successful recovery of AN and it is not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of tactile pleasantness.
Collapse
Affiliation(s)
- Laura Crucianelli
- Department of Clinical, Educational and Health Psychology, University College London, London, UK; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
| | - Benedetta Demartini
- Department of Clinical, Educational and Health Psychology, University College London, London, UK; Department of Health Sciences, University of Milan, Milan, Italy; Psychiatry Unit, ASST Santi Paolo e Carlo, S. Paolo General Hospital, Milan, Italy; Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics, University of Milan, Italy
| | - Diana Goeta
- Department of Health Sciences, University of Milan, Milan, Italy; Psychiatry Unit, ASST Santi Paolo e Carlo, S. Paolo General Hospital, Milan, Italy
| | - Veronica Nisticò
- Department of Clinical, Educational and Health Psychology, University College London, London, UK; Department of Health Sciences, University of Milan, Milan, Italy; Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics, University of Milan, Italy
| | - Alkistis Saramandi
- Department of Clinical, Educational and Health Psychology, University College London, London, UK
| | - Sara Bertelli
- Psychiatry Unit, ASST Santi Paolo e Carlo, S. Paolo General Hospital, Milan, Italy
| | | | - Orsola Gambini
- Department of Health Sciences, University of Milan, Milan, Italy; Psychiatry Unit, ASST Santi Paolo e Carlo, S. Paolo General Hospital, Milan, Italy; Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics, University of Milan, Italy
| | - Aikaterini Fotopoulou
- Department of Clinical, Educational and Health Psychology, University College London, London, UK
| |
Collapse
|
|
45
|
Yilmaz Z, Halvorsen M, Bryois J, Yu D, Thornton LM, Zerwas S, Micali N, Moessner R, Burton CL, Zai G, Erdman L, Kas MJ, Arnold PD, Davis LK, Knowles JA, Breen G, Scharf JM, Nestadt G, Mathews CA, Bulik CM, Mattheisen M, Crowley JJ. Examination of the shared genetic basis of anorexia nervosa and obsessive-compulsive disorder. Mol Psychiatry 2020; 25:2036-2046. [PMID: 30087453 PMCID: PMC6367065 DOI: 10.1038/s41380-018-0115-4] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 03/16/2018] [Accepted: 05/25/2018] [Indexed: 12/22/2022]
Abstract
Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10-7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = -0.25 with body mass index and -0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN-OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.
Collapse
Affiliation(s)
- Zeynep Yilmaz
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Matthew Halvorsen
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Julien Bryois
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Dongmei Yu
- Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Laura M Thornton
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Stephanie Zerwas
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Nadia Micali
- Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- UCL Institute of Child Health, UCL, London, UK
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Rainald Moessner
- Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany
| | - Christie L Burton
- Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Gwyneth Zai
- Neurogenetics Section, Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Lauren Erdman
- Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Martien J Kas
- Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands
- Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Paul D Arnold
- Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada
- Mathison Centre for Mental Health Research & Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Lea K Davis
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - James A Knowles
- SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA
| | - Gerome Breen
- MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Jeremiah M Scharf
- Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Gerald Nestadt
- Department of Psychiatry and Behavioral Science, Johns Hopkins University, Baltimore, MD, USA
| | - Carol A Mathews
- Department of Psychiatry, Genetics Institute, University of Florida, Gainesville, FL, USA
| | - Cynthia M Bulik
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Manuel Mattheisen
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- The Lundbeck Foundation Initiative of Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - James J Crowley
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
| |
Collapse
|
|
46
|
Skowron K, Jasiński K, Kurnik-Łucka M, Stach P, Kalita K, Węglarz WP, Gil K. Hypothalamic and brain stem neurochemical profile in anorectic rats after peripheral administration of kisspeptin-10 using 1 H-nmr spectroscopy in vivo. NMR IN BIOMEDICINE 2020; 33:e4306. [PMID: 32253803 DOI: 10.1002/nbm.4306] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 03/16/2020] [Accepted: 03/17/2020] [Indexed: 06/11/2023]
Abstract
PURPOSE Although anorexia nervosa is classified as a psychiatric disorder associated with socio-environmental and psychological factors, a deeper insight into the dominant neurobiological basis is needed to develop a more effective approach of treatment. Given the high contribution of genetic predisposition and the underlying pathophysiology of neurohormonal circuits, it seems that pharmacological targeting of these mechanisms may provide us with better therapeutic outcomes. METHODS 1 H-NMR spectroscopy was used to measure concentrations of the hypothalamus and brain stem metabolites in an activity-based rodent model (ABA) after subcutaneous administration of kisspeptin-10. Because anorexia mainly affects young women and often leads to hypogonadotropic-hypogonadism, we investigated the influence of this neuropeptide, which is involved in reproductive function by regulating the hypothalamic-pituitary-gonadal axis, on the ABA model development. RESULTS Kisspeptin reinforced food consumption in an activity-based rodent model of anorexia changing a pattern of weight loss. 1 H-NMR spectroscopy of the hypothalamus and brain stem of ABA rats revealed a statistically significant change in the concentration of creatine (Cr; decreased, P = 0.030), phosphocreatine (PCr; increased, P = 0.030), γ-aminobutyric acid (GABA; decreased, P = 0.011), glutathione (GSH; increased, P = 0.011) and inositol (INS; increased, P = 0.047) compared to the control group. Subcutaneous administration of kisspeptin reversed the decrease in GABA (P = 0.018) and Cr (P = 0.030) levels in the hypothalamus as well as restored glutamate (GLU; P = 0.040) level in the brain stem. CONCLUSIONS We suspect that kisspeptin through modulation of hypothalamic GABAergic signaling increases food intake, and thus positively alters brain metabolism.
Collapse
Affiliation(s)
- Kamil Skowron
- Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
| | - Krzysztof Jasiński
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
| | | | - Paulina Stach
- Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
| | - Katarzyna Kalita
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
| | - Władysław P Węglarz
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
| | - Krzysztof Gil
- Department of Pathophysiology, Jagiellonian University Medical College, Kraków, Poland
| |
Collapse
|
|
47
|
Food Addiction among Female Patients Seeking Treatment for an Eating Disorder: Prevalence and Associated Factors. Nutrients 2020; 12:nu12061897. [PMID: 32604734 PMCID: PMC7353200 DOI: 10.3390/nu12061897] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/19/2020] [Accepted: 06/24/2020] [Indexed: 12/16/2022] Open
Abstract
The concept of "food addiction" (FA) has aroused much focus because of evidence for similarities between overeating and substance use disorders (SUDs). However, few studies have explored this concept among the broad spectrum of eating disorders (ED), especially in anorexia nervosa (AN). This study aimed to assess FA prevalence in ED female patients and to determine its associated factors. We recruited a total of 195 adult women with EDs from an ED treatment center. The prevalence of FA diagnosis (Yale Food Addiction Scale) in the whole ED sample was 83.6%; AN restrictive type (AN-R), 61.5%; AN binge-eating/purging type (AN-BP), 87.9%; bulimia nervosa (BN), 97.6%; and binge-eating disorder (BED), 93.3%. The most frequently met criteria of FA were "clinically significant impairment or distress in relation to food", "craving" and "persistent desire or repeated unsuccessful attempts to cut down". An FA diagnosis was independently associated with three variables: presence of recurrent episodes of binge eating, ED severity, and lower interoceptive awareness. In showing an overlap between ED and FA, this study allows for considering EDs, and AN-R in particular, from an "addictive point of view", and thus for designing therapeutic management that draws from those proposed for addictive disorders.
Collapse
|
|
48
|
Villalba Martínez G, Justicia A, Salgado P, Ginés JM, Guardiola R, Cedrón C, Polo M, Delgado-Martínez I, Medrano S, Manero RM, Conesa G, Faus G, Grau A, Elices M, Pérez V. A Randomized Trial of Deep Brain Stimulation to the Subcallosal Cingulate and Nucleus Accumbens in Patients with Treatment-Refractory, Chronic, and Severe Anorexia Nervosa: Initial Results at 6 Months of Follow Up. J Clin Med 2020; 9:jcm9061946. [PMID: 32580399 PMCID: PMC7357090 DOI: 10.3390/jcm9061946] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 06/12/2020] [Accepted: 06/16/2020] [Indexed: 01/28/2023] Open
Abstract
Background: The main objective of this study was to assess the safety and efficacy of deep brain stimulation (DBS) in patients with severe anorexia nervosa (AN). Methods: Eight participants received active DBS to the subcallosal cingulate (SCC) or nucleus accumbens (NAcc) depending on comorbidities (affective or anxiety disorders, respectively) and type of AN. The primary outcome measure was body mass index (BMI). Results: Overall, we found no significant difference (p = 0.84) between mean preoperative and postoperative (month 6) BMI. A BMI reference value (BMI-RV) was calculated. In patients that received preoperative inpatient care to raise the BMI, the BMI-RV was defined as the mean BMI value in the 12 months prior to surgery. In patients that did not require inpatient care, the BMI-RV was defined as the mean BMI in the 3-month period before surgery. This value was compared to the postoperative BMI (month 6), revealing a significant increase (p = 0.02). After 6 months of DBS, five participants showed an increase of ≥10% in the BMI-RV. Quality of life was improved (p = 0.03). Three cases presented cutaneous complications. Conclusion: DBS may be effective for some patients with severe AN. Cutaneous complications were observed. Longer term data are needed.
Collapse
Affiliation(s)
- Gloria Villalba Martínez
- Department of Neurosurgery, Hospital del Mar, 08003 Barcelona, Spain; (G.V.M.); (I.D.-M.); (G.C.)
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain;
| | - Azucena Justicia
- Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain;
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain
| | - Purificación Salgado
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
| | - José María Ginés
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
| | - Rocío Guardiola
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
| | - Carlos Cedrón
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
| | - María Polo
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
| | - Ignacio Delgado-Martínez
- Department of Neurosurgery, Hospital del Mar, 08003 Barcelona, Spain; (G.V.M.); (I.D.-M.); (G.C.)
| | - Santiago Medrano
- Department of Radiology, Hospital del Mar, 08003 Barcelona, Spain;
| | | | - Gerardo Conesa
- Department of Neurosurgery, Hospital del Mar, 08003 Barcelona, Spain; (G.V.M.); (I.D.-M.); (G.C.)
- Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain;
- Department of Surgery, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain
| | - Gustavo Faus
- ITA, Mental Health Specialists, 08036 Barcelona, Spain; (G.F.); (A.G.)
| | - Antoni Grau
- ITA, Mental Health Specialists, 08036 Barcelona, Spain; (G.F.); (A.G.)
| | - Matilde Elices
- Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-933160
| | - Víctor Pérez
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain;
- Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain;
- Institut de Neuropsiquiatria i Adiccions (INAD), Hospital del Mar, 08003 Barcelona, Spain; (P.S.); (J.M.G.); (R.G.); (C.C.); (M.P.)
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain
| |
Collapse
|
|
49
|
Cruz-Carrillo G, Montalvo-Martínez L, Cárdenas-Tueme M, Bernal-Vega S, Maldonado-Ruiz R, Reséndez-Pérez D, Rodríguez-Ríos D, Lund G, Garza-Ocañas L, Camacho-Morales A. Fetal Programming by Methyl Donors Modulates Central Inflammation and Prevents Food Addiction-Like Behavior in Rats. Front Neurosci 2020; 14:452. [PMID: 32581665 PMCID: PMC7283929 DOI: 10.3389/fnins.2020.00452] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 04/14/2020] [Indexed: 12/16/2022] Open
Abstract
Fetal programming by hypercaloric intake leads to food addiction-like behavior and brain pro-inflammatory gene expression in offspring. The role of methylome modulation during programming on central immune activation and addiction-like behavior has not been characterized. We employed a nutritional programming model exposing female Wistar rats to chow diet, cafeteria (CAF), or CAF-methyl donor’s diet from pre-pregnancy to weaning. Addiction-like behavior in offspring was characterized by the operant training response using Skinner boxes. Food intake in offspring was determined after fasting–refeeding schedule and subcutaneous injection of ghrelin. Genome-wide DNA methylation in the nucleus accumbens (NAc) shell was performed by fluorescence polarization, and brain immune activation was evaluated using real-time PCR for pro-inflammatory cytokines (IL-1β, TNF-1α, and IL-6). Molecular effects of methyl modulators [S-adenosylmethionine (SAM) or 5-azatidine (5-AZA)] on pro-inflammatory cytokine expression and phagocytosis were identified in the cultures of immortalized SIM-A9 microglia cells following palmitic acid (100 μM) or LPS (100 nM) stimulation for 6 or 24 h. Our results show that fetal programming by CAF exposure increases the number of offspring subjects and reinforcers under the operant training response schedule, which correlates with an increase in the NAc shell global methylation. Notably, methyl donor’s diet selectively decreases lever-pressing responses for reinforcers and unexpectedly decreases the NAc shell global methylation. Also, programmed offspring by CAF diet shows a selective IL-6 gene expression in the NAc shell, which is reverted to control values by methyl diet exposure. In vitro analysis identified that LPS and palmitic acid activate IL-1β, TNF-1α, and IL-6 gene expression, which is repressed by the methyl donor SAM. Finally, methylation actively represses phagocytosis activity of SIM-A9 microglia cells induced by LPS and palmitic acid stimulation. Our in vivo and in vitro data suggest that fetal programming by methyl donors actively decreases addiction-like behavior to palatable food in the offspring, which correlates with a decrease in NAc shell methylome, expression of pro-inflammatory cytokine genes, and activity of phagocytic microglia. These results support the role of fetal programming in brain methylome on immune activation and food addiction-like behavior in the offspring.
Collapse
Affiliation(s)
- Gabriela Cruz-Carrillo
- Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.,Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Larisa Montalvo-Martínez
- Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.,Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Marcela Cárdenas-Tueme
- Department of Cell Biology and Genetics, College of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Sofia Bernal-Vega
- Department of Cell Biology and Genetics, College of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Roger Maldonado-Ruiz
- Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.,Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Diana Reséndez-Pérez
- Department of Cell Biology and Genetics, College of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | | | - Gertrud Lund
- Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico
| | - Lourdes Garza-Ocañas
- Department of Pharmacology and Toxicology, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| | - Alberto Camacho-Morales
- Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.,Neurometabolism Unit, Center for Research and Development in Health Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico
| |
Collapse
|
|
50
|
Massa MG, Correa SM. Sexes on the brain: Sex as multiple biological variables in the neuronal control of feeding. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165840. [PMID: 32428559 DOI: 10.1016/j.bbadis.2020.165840] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 05/05/2020] [Accepted: 05/13/2020] [Indexed: 12/21/2022]
Abstract
Neuronal interactions at the level of vagal, homeostatic, and hedonic circuitry work to regulate the neuronal control of feeding. This integrative system appears to vary across sex and gender in the animal and human worlds. Most feeding research investigating these variations across sex and gender focus on how the organizational and activational mechanisms of hormones contribute to these differences. However, in limited studies spanning both the central and peripheral nervous systems, sex differences in feeding have been shown to manifest not just at the level of the hormonal, but also at the chromosomal, epigenetic, cellular, and even circuitry levels to alter food intake. In this review, we provide a brief orientation to the current understanding of how these neuronal systems interact before dissecting selected studies from the recent literature to exemplify how feeding physiology at all levels can be affected by the various components of sex.
Collapse
Affiliation(s)
- Megan G Massa
- Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, United States of America; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, CA, United States of America; Neuroscience Interdepartmental Doctoral Program, University of California, Los Angeles, CA, United States of America.
| | - Stephanie M Correa
- Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, United States of America; Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, CA, United States of America.
| |
Collapse
|