{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:40:07Z","timestamp":1790386807958,"version":"4.1.0"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:p>Depression is an umbrella term used to describe a mood disorder with a broad spectrum of symptoms including a persistent feeling of sadness, loss of interest, and deficits in social behavior. Epigenetic research bridges the environmental and genetic landscape and has the potential to exponentially improve our understanding of such a complex disorder. Depression is also a sexually dimorphic disorder and variations exist within epigenetic modification sites between sexes. These sex-specific mediators may impact behavioral symptomology and could serve as therapeutic targets for treatments to improve behavioral deficits. This mini review will focus on the social behavior perspective of depression and specifically explore the sexually different epigenetic modifications on depression.<\/jats:p>","DOI":"10.3389\/fncir.2021.768571","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T23:37:12Z","timestamp":1634773032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies"],"prefix":"10.3389","volume":"15","author":[{"given":"Branden","family":"Cahill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Poelker-Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan F.","family":"Prather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/nrn1884","article-title":"Meeting of minds: the medial frontal cortex and social cognition.","volume":"7","author":"Amodio","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.euroneuro.2013.07.012","article-title":"Maternal separation is associated with DNA methylation and behavioural changes in adult rats.","volume":"24","author":"Anier","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00510","article-title":"Oxytocin and vasopressin receptor gene polymorphisms: role in social and psychiatric traits.","volume":"9","author":"Aspe-Sanchez","year":"2015","journal-title":"Front. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/sj.mp.4001565","article-title":"Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder.","volume":"10","author":"Aston","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1006\/hbeh.2001.1653","article-title":"Social stress induces glucocorticoid resistance in subordinate animals.","volume":"39","author":"Avitsur","year":"2001","journal-title":"Horm. Behav."},{"key":"B6","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications.","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.neubiorev.2010.07.002","article-title":"Sex bias in neuroscience and biomedical research.","volume":"35","author":"Beery","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jad.2006.04.029","article-title":"Different gender response to serotonergic and noradrenergic antidepressants. A comparative study of the efficacy of citalopram and reboxetine.","volume":"95","author":"Berlanga","year":"2006","journal-title":"J. Affect. Disord."},{"key":"B9","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/nrn1846","article-title":"New approaches to antidepressant drug discovery: beyond monoamines.","volume":"7","author":"Berton","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/s0165-0327(99)00004-x","article-title":"Lifetime suicide risk in major depression: sex and age determinants.","volume":"55","author":"Blair-West","year":"1999","journal-title":"J. Affect. Disord."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1210\/en.2018-00217","article-title":"Chronic variable stress induces sex-specific alterations in social behavior and neuropeptide expression in the mouse.","volume":"159","author":"Borrow","year":"2018","journal-title":"Endocrinology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.neuropharm.2011.08.017","article-title":"Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner.","volume":"62","author":"Brummelte","year":"2012","journal-title":"Neuropharmacology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.2147\/PPA.S110632","article-title":"Long-term antidepressant use: patient perspectives of benefits and adverse effects.","volume":"10","author":"Cartwright","year":"2016","journal-title":"Patient Prefer. Adherence"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2020.100249","article-title":"Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system.","volume":"13","author":"Catale","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"B15","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.omtn.2020.05.001","article-title":"MicroRNA-206 regulates stress-provoked aggressive behaviors in post-weaning social isolation mice.","volume":"20","author":"Chang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B16","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jad.2015.08.065","article-title":"Gender differences in mood stabilizer medications prescribed to Veterans with serious mental illness.","volume":"188","author":"Charlotte","year":"2015","journal-title":"J. Affect. Disord."},{"key":"B17","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1017\/S1461145710001422","article-title":"The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression.","volume":"14","author":"Chen","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1080\/15592294.2019.1700628","article-title":"Longitudinal DNA methylation changes at MET may alter HGF\/c-MET signalling in adolescents at risk for depression.","volume":"15","author":"Ciuculete","year":"2020","journal-title":"Epigenetics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1001\/jamapsychiatry.2016.2586","article-title":"Toward an evidence-based, operational definition of treatment-resistant depression: when enough is enough.","volume":"74","author":"Conway","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.biopsych.2007.03.001","article-title":"Evolving knowledge of sex differences in brain structure, function, and chemistry.","volume":"62","author":"Cosgrove","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.pnpbp.2018.08.003","article-title":"Long-term impact of chronic variable stress in adolescence versus adulthood.","volume":"88","author":"Cotella","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/ejn.14582","article-title":"Paternal transgenerational epigenetic mechanisms mediating stress phenotypes of offspring.","volume":"53","author":"Cunningham","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0146-2","article-title":"Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress.","volume":"8","author":"Dickson","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"B24","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2011.05.005","article-title":"Paternal transmission of stress-induced pathologies.","volume":"70","author":"Dietz","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yfrne.2015.04.003","article-title":"Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior.","volume":"40","author":"Dumais","year":"2016","journal-title":"Front. Neuroendocrinol."},{"key":"B26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1037\/0033-2909.100.3.309","article-title":"Gender and aggressive behavior: a meta-analytic review of the social psychological literature.","volume":"100","author":"Eagly","year":"1986","journal-title":"Psychol. Bull."},{"key":"B27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.brainres.2011.01.078","article-title":"Gender-specific response of brain corticosteroid receptors to stress and fluoxetine.","volume":"1384","author":"Elakovic","year":"2011","journal-title":"Brain Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/nn.2642","article-title":"Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice.","volume":"13","author":"Elliott","year":"2010","journal-title":"Nat. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58297-9","article-title":"Depressive symptoms are associated with social isolation in face-to-face interaction networks.","volume":"10","author":"Elmer","year":"2020","journal-title":"Sci. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/mp.2009.35","article-title":"Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers.","volume":"14","author":"Ernst","year":"","journal-title":"Mol. Psychiatry"},{"key":"B31","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1001\/archpsyc.66.1.22","article-title":"Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers.","volume":"66","author":"Ernst","year":"","journal-title":"Arch. Gen. Psychiatry"},{"key":"B32","first-page":"37","article-title":"Weight gain and antidepressants.","author":"Fava","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1017\/S1461145709991167","article-title":"Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers.","volume":"13","author":"Fiori","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1001\/archinte.164.9.1010","article-title":"Depression and C-reactive protein in US adults: data from the third national health and nutrition examination survey.","volume":"164","author":"Ford","year":"2004","journal-title":"Arch. Intern. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2010.05.036","article-title":"Epigenetic transmission of the impact of early stress across generations.","volume":"68","author":"Franklin","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nn.3695","article-title":"Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice.","volume":"17","author":"Gapp","year":"2014","journal-title":"Nat. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1038\/s41380-018-0271-6","article-title":"Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma.","volume":"25","author":"Gapp","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s10571-010-9606-9","article-title":"Adrenal responses to stress.","volume":"30","author":"Goldstein","year":"2010","journal-title":"Cell. Mol. Neurobiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/cercor\/11.6.490","article-title":"Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.","volume":"11","author":"Goldstein","year":"2001","journal-title":"Cereb. Cortex"},{"key":"B40","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.physbeh.2018.09.001","article-title":"Social instability in female rodents as a model of stress related disorders: a systematic review.","volume":"196","author":"Goni-Balentziaga","year":"2018","journal-title":"Physiol. Behav."},{"key":"B41","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1002\/hipo.20907","article-title":"Early life stress stimulates hippocampal reelin gene expression in a sex-specific manner: evidence for corticosterone-mediated action.","volume":"22","author":"Gross","year":"2012","journal-title":"Hippocampus"},{"key":"B42","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1037\/a0026712","article-title":"Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21.","volume":"26","author":"Gur","year":"2012","journal-title":"Neuropsychology"},{"key":"B43","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1523\/JNEUROSCI.19-10-04065.1999","article-title":"Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance.","volume":"19","author":"Gur","year":"1999","journal-title":"J. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nrm3838","article-title":"Regulation of microRNA biogenesis.","volume":"15","author":"Ha","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/s0361-9230(99)00087-8","article-title":"Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats.","volume":"50","author":"Haller","year":"1999","journal-title":"Brain Res. Bull."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1529-1006.2007.00032.x","article-title":"The science of sex differences in science and mathematics.","volume":"8","author":"Halpern","year":"2007","journal-title":"Psychol. Sci. Public Interest."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1093\/molbev\/msh104","article-title":"Functional microsatellite polymorphism associated with divergent social structure in vole species.","volume":"21","author":"Hammock","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.neuroscience.2009.01.059","article-title":"Chronic social instability stress in female rats: a potential animal model for female depression.","volume":"159","author":"Herzog","year":"2009","journal-title":"Neuroscience"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/cells8090943","article-title":"Mismatched prenatal and postnatal maternal depressive symptoms and child behaviours: a sex-dependent role for NR3C1 DNA methylation in the Wirral Child Health and Development Study.","volume":"8","author":"Hill","year":"2019","journal-title":"Cells"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1037\/a0038550","article-title":"A brief history of the development of antidepressant drugs: from monoamines to glutamate.","volume":"23","author":"Hillhouse","year":"2015","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"268","DOI":"10.4088\/jcp.v61n0405","article-title":"Social functioning in depression: a review.","volume":"61","author":"Hirschfeld","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"B52","doi-asserted-by":"publisher","first-page":"16362","DOI":"10.1523\/JNEUROSCI.1392-15.2015","article-title":"Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress.","volume":"35","author":"Hodes","year":"2015","journal-title":"J. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-00948-6","article-title":"Association between DNA methylation levels in brain tissue and late-life depression in community-based participants.","volume":"10","author":"Huls","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"B54","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1073\/pnas.1316909110","article-title":"Sex differences in the structural connectome of the human brain.","volume":"111","author":"Ingalhalikar","year":"2014","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B55","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.biopsych.2017.07.014","article-title":"Vicarious social defeat stress induces depression-related outcomes in female mice.","volume":"83","author":"Iniguez","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-015-0156-3","article-title":"Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders.","volume":"7","author":"Jawahar","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"B57","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/bs.pmbts.2018.03.003","article-title":"Transgenerational epigenetics of traumatic stress.","volume":"158","author":"Jawaid","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3109\/00048678709160898","article-title":"Sex and age differences in depression: a quantitative synthesis of published research.","volume":"21","author":"Jorm","year":"1987","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"B59","doi-asserted-by":"publisher","first-page":"154","DOI":"10.4236\/ojd.2014.34019","article-title":"Social connectedness predicts lower loneliness and depressive symptoms over time in adolescents.","volume":"3","author":"Jose","year":"2014","journal-title":"Open J. Depress."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1017\/s0033291798008198","article-title":"The assessment of dependence in the study of stressful life events: validation using a twin design.","volume":"29","author":"Kendler","year":"1999","journal-title":"Psychol. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1146\/annurev.psych.48.1.191","article-title":"The effects of stressful life events on depression.","volume":"48","author":"Kessler","year":"1997","journal-title":"Annu. Rev. Psychol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/s0165-0327(02)00426-3","article-title":"Epidemiology of women and depression.","volume":"74","author":"Kessler","year":"2003","journal-title":"J. Affect. Disord."},{"key":"B63","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1097\/01.jcp.0000168879.03169.ce","article-title":"Sex differences in antidepressant response in recent antidepressant clinical trials.","volume":"25","author":"Khan","year":"2005","journal-title":"J. Clin. Psychopharmacol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.cell.2019.09.020","article-title":"Multimodal analysis of cell types in a hypothalamic node controlling social behavior.","volume":"179","author":"Kim","year":"2019","journal-title":"Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrm2143","article-title":"Regulation of histone methylation by demethylimination and demethylation.","volume":"8","author":"Klose","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1176\/appi.ajp.157.9.1445","article-title":"Gender differences in treatment response to sertraline versus imipramine in chronic depression.","volume":"157","author":"Kornstein","year":"2000","journal-title":"Am. J. Psychiatry"},{"key":"B67","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/s41593-021-00814-8","article-title":"Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons.","volume":"24","author":"Kronman","year":"2021","journal-title":"Nat. Neurosci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/nm.4386","article-title":"Sex-specific transcriptional signatures in human depression.","volume":"23","author":"Labonte","year":"2017","journal-title":"Nat. Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1176\/appi.ajp.2012.12050627","article-title":"Genome-wide methylation changes in the brains of suicide completers.","volume":"170","author":"Labonte","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"B70","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1001\/archgenpsychiatry.2011.2287","article-title":"Genome-wide epigenetic regulation by early-life trauma.","volume":"69","author":"Labonte","year":"","journal-title":"Arch. Gen. Psychiatry"},{"key":"B71","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.biopsych.2012.01.034","article-title":"Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse.","volume":"72","author":"Labonte","year":"","journal-title":"Biol. Psychiatry"},{"key":"B72","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1016\/j.biopsych.2009.01.024","article-title":"Role of nuclear factor kappaB in ovarian hormone-mediated stress hypersensitivity in female mice.","volume":"65","author":"LaPlant","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1038\/nn.2619","article-title":"Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.","volume":"13","author":"LaPlant","year":"2010","journal-title":"Nat. Neurosci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.biopsych.2017.01.021","article-title":"Replicable and coupled changes in innate and adaptive immune gene expression in two case-control studies of blood microarrays in major depressive disorder.","volume":"83","author":"Leday","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.573107","article-title":"Differences in DNA methylation reprogramming underlie the sexual dimorphism of behavioral disorder caused by prenatal stress in rats.","volume":"14","author":"Lei","year":"2020","journal-title":"Front. Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2007.01.015","article-title":"The role of chromatin during transcription.","volume":"128","author":"Li","year":"2007","journal-title":"Cell"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.02.765","article-title":"Role of CCL5 and its receptors in female social defeat stress.","volume":"89","author":"Lin","year":"2021","journal-title":"Biological. Psychiatry"},{"key":"B78","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/mp.2012.38","article-title":"Epigenetic regulation of BDNF expression according to antidepressant response.","volume":"18","author":"Lopez","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"B79","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.bbr.2015.02.009","article-title":"Sex differences in the stress response in SD rats.","volume":"284","author":"Lu","year":"2015","journal-title":"Behav. Brain Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1080\/15622975.2018.1500029","article-title":"Chronic social defeat stress differentially regulates the expression of BDNF transcripts and epigenetic modifying enzymes in susceptible and resilient mice.","volume":"20","author":"Mallei","year":"2019","journal-title":"World J. Biol. Psychiatry"},{"key":"B81","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/s0165-1781(00)00162-1","article-title":"A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.","volume":"95","author":"Manuck","year":"2000","journal-title":"Psychiatry Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.euroneuro.2019.11.004","article-title":"Gene expression signature of antidepressant treatment response\/non-response in Flinders Sensitive Line rats subjected to maternal separation.","volume":"31","author":"Marchetti","year":"2020","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s00127-016-1178-7","article-title":"Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis.","volume":"51","author":"Matthews","year":"2016","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"12815","DOI":"10.1523\/jneurosci.3331-09.2009","article-title":"The epigenetics of sex differences in the brain.","volume":"29","author":"McCarthy","year":"2009","journal-title":"J. Neurosci."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002085","article-title":"Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.","volume":"3","author":"McGowan","year":"2008","journal-title":"PLoS One"},{"key":"B86","doi-asserted-by":"publisher","first-page":"277","DOI":"10.2174\/2666082215666191029141418","article-title":"Epigenetics, gender, and sex in the diagnosis of depression.","volume":"15","author":"Mehl-Madrona","year":"2019","journal-title":"Curr. Psychiatry Res. Rev."},{"key":"B87","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.neubiorev.2006.05.003","article-title":"Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains.","volume":"31","author":"Millstein","year":"2007","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239335","article-title":"Epigenetic marks and their relationship with BDNF in the brain of suicide victims.","volume":"15","author":"Misztak","year":"2020","journal-title":"PLoS One"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2018.00157","article-title":"Early life stress in rodents: animal models of illness or resilience?","volume":"12","author":"Murthy","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/s41593-020-0621-y","article-title":"Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.","volume":"23","author":"Nagy","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/mp.2014.21","article-title":"Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.","volume":"20","author":"Nagy","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"B92","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1192\/bjp.bp.115.180752","article-title":"Childhood maltreatment and characteristics of adult depression: meta-analysis.","volume":"210","author":"Nelson","year":"2017","journal-title":"Br. J. Psychiatry"},{"key":"B93","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.1749-6632.1999.tb09271.x","article-title":"The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network.","volume":"877","author":"Newman","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1176\/appi.ajp.159.8.1265","article-title":"Parental depression: animal models of an adverse life event.","volume":"159","author":"Newport","year":"2002","journal-title":"Am. J. Psychiatry"},{"key":"B95","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.biopsych.2015.05.017","article-title":"Early-life adversity and physical and emotional health across the lifespan: a neuroimmune network hypothesis.","volume":"80","author":"Nusslock","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"B96","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1210\/edrv.22.4.0436","article-title":"Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.","volume":"22","author":"Pacak","year":"2001","journal-title":"Endocr. Rev."},{"key":"B97","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.bbi.2020.11.027","article-title":"HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women.","volume":"92","author":"Palma-Gudiel","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"B98","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.cobeha.2017.02.007","article-title":"Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes.","volume":"14","author":"Pang","year":"2017","journal-title":"Curr. Opin. Behav. Sci."},{"key":"B99","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.ceb.2005.02.006","article-title":"Methylation of histones: playing memory with DNA.","volume":"17","author":"Peters","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.neuroscience.2012.03.003","article-title":"5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor mRNA modulation by antidepressant treatment in the chronic mild stress model of depression: sex differences exposed.","volume":"210","author":"Pitychoutis","year":"2012","journal-title":"Neuroscience"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1007\/s00702-019-02084-y","article-title":"Animal models of major depression: drawbacks and challenges.","volume":"126","author":"Planchez","year":"2019","journal-title":"J. Neural. Transm."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1038\/nbt.1685","article-title":"Epigenetic modifications and human disease.","volume":"28","author":"Portela","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.biopsych.2008.05.028","article-title":"GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes.","volume":"64","author":"Poulter","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.586904","article-title":"Depressive-like behaviors induced by chronic social defeat stress are associated with HDAC7 reduction in the nucleus accumbens.","volume":"11","author":"Qian","year":"2020","journal-title":"Front. Psychiatry"},{"key":"B105","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1601-183X.2011.00681.x","article-title":"A role for BDNF\/TrkB signaling in behavioral and physiological consequences of social defeat stress.","volume":"10","author":"Razzoli","year":"2011","journal-title":"Genes Brain Behav."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2020.110068","article-title":"Social defeat stress in adult mice causes alterations in gene expression, alternative splicing, and the epigenetic landscape of H3K4me3 in the prefrontal cortex: an impact of early-life stress.","volume":"106","author":"Reshetnikov","year":"2021","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B107","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jad.2009.10.029","article-title":"Trajectories of recovery of social and physical functioning in major depression, dysthymic disorder and double depression: a 3-year follow-up.","volume":"124","author":"Rhebergen","year":"2010","journal-title":"J. Affect. Disord."},{"key":"B108","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1093\/ijnp\/pyx048","article-title":"Sex-dependent effects of stress on immobility behavior and VTA dopamine neuron activity: modulation by ketamine.","volume":"20","author":"Rincon-Cortes","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0278-2626(03)00277-X","article-title":"The functions of the orbitofrontal cortex.","volume":"55","author":"Rolls","year":"2004","journal-title":"Brain Cogn."},{"key":"B110","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR\u2217D report.","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"B111","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.psyneuen.2013.11.008","article-title":"Sex differences in response to chronic mild stress and congenital serotonin deficiency.","volume":"40","author":"Sachs","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"B112","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s12031-019-01446-1","article-title":"Relation of promoter methylation of the oxytocin gene to stressful life events and depression severity.","volume":"70","author":"Sanwald","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"B113","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.biopsych.2019.12.029","article-title":"Shared transcriptional signatures in major depressive disorder and mouse chronic stress models.","volume":"88","author":"Scarpa","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"B114","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1159\/000435778","article-title":"Epigenetic dysregulation in the prefrontal cortex of suicide completers.","volume":"146","author":"Schneider","year":"2015","journal-title":"Cytogenet. Genome Res."},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-014-0017-3","article-title":"Sex differences in mood disorders: perspectives from humans and rodent models.","volume":"5","author":"Seney","year":"2014","journal-title":"Biol. Sex Differ."},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176331","article-title":"Effects of early life stress on epigenetic changes of the glucocorticoid receptor 17 promoter during adulthood.","volume":"21","author":"Seo","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B117","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.physbeh.2009.02.016","article-title":"Genetic, epigenetic and environmental impact on sex differences in social behavior.","volume":"97","author":"Shepard","year":"2009","journal-title":"Physiol. Behav."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2016.06.038","article-title":"Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: relevance for sex differences in stress-related disorders.","volume":"332","author":"Shepard","year":"2016","journal-title":"Neuroscience"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.109","article-title":"Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring.","volume":"6","author":"Short","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"B120","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/2211-5463.12581","article-title":"Differential regulation of brain-derived neurotrophic factor (BDNF) expression in sensory neuron axons by miRNA-206.","volume":"9","author":"Shrestha","year":"2019","journal-title":"FEBS Open Bio."},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-020-09337-y","article-title":"Early life stress and development: potential mechanisms for adverse outcomes.","volume":"12","author":"Smith","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"B122","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1111\/jgs.15966","article-title":"Adverse effects of pharmacologic treatments of major depression in older adults.","volume":"67","author":"Sobieraj","year":"2019","journal-title":"J. Am. Geriatr. Soc."},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-7-9","article-title":"Update in the methodology of the chronic stress paradigm: internal control matters.","volume":"7","author":"Strekalova","year":"2011","journal-title":"Behav. Brain Funct."},{"key":"B124","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1007\/s12035-020-02224-6","article-title":"Maternal separation-induced histone acetylation correlates with BDNF-programmed synaptic changes in an animal model of PTSD with sex differences.","volume":"58","author":"Sun","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nn1659","article-title":"Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action.","volume":"9","author":"Tsankova","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B126","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.psychres.2007.10.017","article-title":"Childhood maltreatment and adult personality disorder symptoms: influence of maltreatment type.","volume":"165","author":"Tyrka","year":"2009","journal-title":"Psychiatry Res."},{"key":"B127","doi-asserted-by":"publisher","first-page":"9470","DOI":"10.1073\/pnas.0910794107","article-title":"Epigenetic and immune function profiles associated with posttraumatic stress disorder.","volume":"107","author":"Uddin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.4088\/JCP.10m06419","article-title":"Early and delayed onset of response to antidepressants in individual trajectories of change during treatment of major depression: a secondary analysis of data from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study.","volume":"72","author":"Uher","year":"2011","journal-title":"J. Clin. Psychiatry"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00355","article-title":"Early life stress and serotonin transporter gene variation interact to affect the transcription of the glucocorticoid and mineralocorticoid receptors, and the co-chaperone FKBP5, in the adult rat brain.","volume":"8","author":"van der Doelen","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"B130","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.bbr.2019.03.025","article-title":"Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats.","volume":"366","author":"Viana Borges","year":"2019","journal-title":"Behav. Brain Res."},{"key":"B131","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.chiabu.2006.04.010","article-title":"Child multi-type maltreatment and associated depression and PTSD symptoms: the role of social support and stress.","volume":"31","author":"Vranceanu","year":"2007","journal-title":"Child Abuse Negl."},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.02.964","article-title":"Sex-specific transcriptional changes in response to adolescent social stress in the brain\u2019s reward circuitry.","author":"Walker","year":"2021","journal-title":"Biol. Psychiatry."},{"key":"B133","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4068\/cmj.2018.54.2.101","article-title":"Addressing the side effects of contemporary antidepressant drugs: a comprehensive review.","volume":"54","author":"Wang","year":"2018","journal-title":"Chonnam Med. J."},{"key":"B134","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.biopsych.2012.06.006","article-title":"Neurobiological sequelae of witnessing stressful events in adult mice.","volume":"73","author":"Warren","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"B135","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1001\/archpsyc.1977.01770130100011","article-title":"Sex differences and the epidemiology of depression.","volume":"34","author":"Weissman","year":"1977","journal-title":"Arch. Gen. Psychiatry"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005744","article-title":"Neuronal activity-regulated gene transcription in synapse development and cognitive function.","volume":"3","author":"West","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0682-5","article-title":"Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.","volume":"11","author":"Wiechmann","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"B138","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ynstr.2016.08.001","article-title":"Reliability of the chronic mild stress model of depression: a user survey.","volume":"6","author":"Willner","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"B139","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.4161\/epi.22363","article-title":"Epigenetic regulation of the glucocorticoid receptor promoter 1(7) in adult rats.","volume":"7","author":"Witzmann","year":"2012","journal-title":"Epigenetics"},{"key":"B140","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.neuint.2013.09.019","article-title":"Gender differences in CMS and the effects of antidepressant venlafaxine in rats.","volume":"63","author":"Xing","year":"2013","journal-title":"Neurochem. Int."},{"key":"B141","doi-asserted-by":"publisher","first-page":"263","DOI":"10.4196\/kjpp.2014.18.3.263","article-title":"Chronic non-social stress affects depressive behaviors but not anxiety in mice.","volume":"18","author":"Yoon","year":"2014","journal-title":"Korean J. Physiol. Pharmacol."}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.768571\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T23:37:17Z","timestamp":1634773037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.768571\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":141,"alternative-id":["10.3389\/fncir.2021.768571"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2021.768571","relation":{},"ISSN":["1662-5110"],"issn-type":[{"value":"1662-5110","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]},"article-number":"768571"}}