Biological Underpinnings of Trauma and Post-Traumatic Stress Disorder: Focusing on Genetics and Epigenetics

References

• Bonanno GA . Loss, trauma, and human resilience: have we underestimated the human capacity to thrive after extremely aversive events?Am. Psychol.59 ( 1 ), 20 – 28 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Bisson JI , CosgroveS , LewisC , RobertNP . Post-traumatic stress disorder . BMJ351 , h6161 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association . Diagnostic And Statistical Manual Of Mental Disorders (5th Edition) . American Psychiatric Publishing , VA, USA ( 2013 ).
   Google Scholar
• Hauffa R , RiefW , BrahlerE , MartinA , MewesR , GlaesmerH . Lifetime traumatic experiences and post-traumatic stress disorder in the German population: results of a representative population survey . J. Nerv. Ment. Dis.199 ( 12 ), 934 – 939 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Reynolds K , PietrzakRH , MackenzieCS , ChouKL , SareenJ . Post-traumatic stress disorder across the adult lifespan: findings from a nationally representative survey . Am. J. Geriatr. Psychiatry24 ( 1 ), 81 – 93 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Darves-Bornoz JM , AlonsoJ , De GirolamoGet al. Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey . J. Trauma Stress21 ( 5 ), 455 – 462 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Creamer M , BurgessP , McFarlaneAC . Post-traumatic stress disorder: findings from the Australian National Survey of Mental Health and Well-being . Psychol. Med.31 ( 7 ), 1237 – 1247 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Yehuda R , HalliganSL , BiererLM . Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring . J. Psychiatr. Res.35 ( 5 ), 261 – 270 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Sartor CE , GrantJD , LynskeyMTet al. Common heritable contributions to low-risk trauma, high-risk trauma, post-traumatic stress disorder, and major depression . Arch. Gen. Psychiatry69 ( 3 ), 293 – 299 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Lyons MJ , GoldbergJ , EisenSAet al. Do genes influence exposure to trauma? A twin study of combat . Am. J. Med. Genet.48 ( 1 ), 22 – 27 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• True WR , RiceJ , EisenSAet al. A twin study of genetic and environmental contributions to liability for post-traumatic stress symptoms . Arch. Gen. Psychiatry50 ( 4 ), 257 – 264 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Stein MB , JangKL , TaylorS , VernonPA , LivesleyWJ . Genetic and environmental influences on trauma exposure and post-traumatic stress disorder symptoms: a twin study . Am. J. Psychiatry159 ( 10 ), 1675 – 1681 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Jang KL , SteinMB , TaylorS , AsmundsonGJ , LivesleyWJ . Exposure to traumatic events and experiences: aetiological relationships with personality function . Psychiatry Res.120 ( 1 ), 61 – 69 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Amstadter AB , AggenSH , KnudsenGP , Reichborn-KjennerudT , KendlerKS . A population-based study of familial and individual-specific environmental contributions to traumatic event exposure and post-traumatic stress disorder symptoms in a Norwegian twin sample . Twin Res. Hum. Genet.15 ( 5 ), 656 – 662 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Dragan WL , OniszczenkoW . The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors . Anxiety Stress Coping22 ( 5 ), 483 – 495 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Nelson EC , HeathAC , LynskeyMTet al. PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals . Addict. Biol.19 ( 4 ), 700 – 707 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Comings DE , MuhlemanD , GysinR . Dopamine D2 receptor (DRD2) gene and susceptibility to post-traumatic stress disorder: a study and replication . Biol. Psychiatry40 ( 5 ), 368 – 372 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Young RM , LawfordBR , NobleEPet al. Harmful drinking in military veterans with post-traumatic stress disorder: association with the D2 dopamine receptor A1 allele . Alcohol Alcohol.37 ( 5 ), 451 – 456 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Voisey J , SwagellCD , HughesIPet al. The DRD2 gene 957C>T polymorphism is associated with post-traumatic stress disorder in war veterans . Depress. Anxiety26 ( 1 ), 28 – 33 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Voisey J , YoungRM , LawfordBR , MorrisCP . Progress towards understanding the genetics of post-traumatic stress disorder . J. Anxiety Disord.28 ( 8 ), 873 – 883 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Chang SC , KoenenKC , GaleaSet al. Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study . PLoS ONE7 ( 6 ), e39184 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Drury SS , TheallKP , KeatsBJ , ScheeringaM . The role of the dopamine transporter (DAT) in the development of PTSD in preschool children . J. Trauma Stress22 ( 6 ), 534 – 539 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Koenen KC , UddinM , ChangSCet al. SLC6A4 methylation modifies the effect of the number of traumatic events on risk for post-traumatic stress disorder . Depress. Anxiety28 ( 8 ), 639 – 647 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Mellman TA , AlimT , BrownDDet al. Serotonin polymorphisms and post-traumatic stress disorder in a trauma exposed African–American population . Depress. Anxiety26 ( 11 ), 993 – 997 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Cornelis MC , NugentNR , AmstadterAB , KoenenKC . Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies . Curr. Psychiatry Rep.12 ( 4 ), 313 – 326 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Koenen KC , AielloAE , BakshisEet al. Modification of the association between serotonin transporter genotype and risk of post-traumatic stress disorder in adults by county-level social environment . Am. J. Epidemiol.169 ( 6 ), 704 – 711 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Kilpatrick DG , KoenenKC , RuggieroKJet al. The serotonin transporter genotype and social support and moderation of post-traumatic stress disorder and depression in hurricane-exposed adults . Am. J. Psychiatry164 ( 11 ), 1693 – 1699 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Xie P , KranzlerHR , PolingJet al. Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on post-traumatic stress disorder diagnosis in 2 independent populations . Arch. Gen. Psychiatry66 ( 11 ), 1201 – 1209 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Gressier F , CalatiR , BalestriMet al. The 5-HTTLPR polymorphism and post-traumatic stress disorder: a meta-analysis . J. Trauma Stress26 ( 6 ), 645 – 653 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Van IMH , CaspersK , Bakermans-KranenburgMJ , BeachSR , PhilibertR . Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma . Biol. Psychiatry68 ( 5 ), 405 – 407 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Alexander N , WankerlM , HennigJet al. DNA methylation profiles within the serotonin transporter gene moderate the association of 5-HTTLPR and cortisol stress reactivity . Transl. Psychiatry.4 , e443 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• White S , AciernoR , RuggieroKJet al. Association of CRHR1 variants and post-traumatic stress symptoms in hurricane exposed adults . J. Anxiety Disord.27 ( 7 ), 678 – 683 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Dunn EC , SolovieffN , LoweSRet al. Interaction between genetic variants and exposure to Hurricane Katrina on post-traumatic stress and post-traumatic growth: a prospective analysis of low income adults . J. Affect. Disord.152–154 , 243 – 249 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Bachmann AW , SedgleyTL , JacksonRV , GibsonJN , YoungRM , TorpyDJ . Glucocorticoid receptor polymorphisms and post-traumatic stress disorder . Psychoneuroendocrinology30 ( 3 ), 297 – 306 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Yehuda R , FloryJD , BiererLMet al. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with post-traumatic stress disorder . Biol. Psychiatry77 ( 4 ), 356 – 364 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Labonte B , AzoulayN , YerkoV , TureckiG , BrunetA . Epigenetic modulation of glucocorticoid receptors in post-traumatic stress disorder . Transl. Psychiatry.4 , e368 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Vukojevic V , KolassaIT , FastenrathMet al. Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors . J. Neurosci.34 ( 31 ), 10274 – 10284 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Schechter DS , MoserDA , Paoloni-GiacobinoAet al. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure . Front. Psychol.6 , 690 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Binder EB , BradleyRG , LiuWet al. Association of FKBP5 polymorphisms and childhood abuse with risk of post-traumatic stress disorder symptoms in adults . JAMA299 ( 11 ), 1291 – 1305 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Xie P , KranzlerHR , PolingJet al. Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder . Neuropsychopharmacology35 ( 8 ), 1684 – 1692 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Klengel T , MehtaD , AnackerCet al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions . Nat. Neurosci.16 ( 1 ), 33 – 41 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Ressler KJ , MercerKB , BradleyBet al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor . Nature470 ( 7335 ), 492 – 497 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Almli LM , MercerKB , KerleyKet al. ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African–American females . Am. J. Med. Genet. B Neuropsychiatr. Genet.162b ( 3 ), 262 – 272 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Wang L , CaoC , WangR , QingY , ZhangJ , ZhangXY . PAC1 receptor (ADCYAP1R1) genotype is associated with PTSD’s emotional numbing symptoms in Chinese earthquake survivors . J. Affect. Disord.150 ( 1 ), 156 – 159 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kim TY , ChungHG , ShinHSet al. Apolipoprotein E gene polymorphism, alcohol use, and their interactions in combat-related post-traumatic stress disorder . Depress. Anxiety30 ( 12 ), 1194 – 1201 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Pivac N , Kozaric-KovacicD , Grubisic-IlicMet al. The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in post-traumatic stress disorder . World J. Biol Psychiatry13 ( 4 ), 306 – 311 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Felmingham KL , Dobson-StoneC , SchofieldPR , QuirkGJ , BryantRA . The brain-derived neurotrophic factor Val66Met polymorphism predicts response to exposure therapy in post-traumatic stress disorder . Biol. Psychiatry73 ( 11 ), 1059 – 1063 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Zhang H , OzbayF , LappalainenJet al. Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer’s disease, affective disorders, post-traumatic stress disorder, schizophrenia, and substance dependence . Am. J. Med. Genet. B Neuropsychiatr. Genet.141b ( 4 ), 387 – 393 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Moser DA , Paoloni-GiacobinoA , StenzLet al. BDNF methylation and maternal brain activity in a violence-related sample . PLoS ONE10 ( 12 ), e0143427 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Lu AT , OgdieMN , JarvelinMRet al. Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder . Am. J. Med. Genet. B Neuropsychiatr. Genet.147b ( 8 ), 1488 – 1494 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Norrholm SD , JovanovicT , SmithAKet al. Differential genetic and epigenetic regulation of catechol-O-methyltransferase is associated with impaired fear inhibition in post-traumatic stress disorder . Front. Behav. Neurosci.7 , 30 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Michopoulos V , RothbaumAO , JovanovicTet al. Association of CRP genetic variation and CRP level with elevated PTSD symptoms and physiological responses in a civilian population with high levels of trauma . Am. J. Psychiatry172 ( 4 ), 353 – 362 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Uddin M , GaleaS , ChangSCet al. Gene expression and methylation signatures of MAN2C1 are associated with PTSD . Dis. Markers.30 ( 2–3 ), 111 – 121 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Andero R , BrothersSP , JovanovicTet al. Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD . Sci. Transl. Med.5 ( 188 ), 188ra173 ( 2013 ).
   Web of Science ®Google Scholar
• De Quervain DJ , KolassaIT , AckermannSet al. PKCalpha is genetically linked to memory capacity in healthy subjects and to risk for post-traumatic stress disorder in genocide survivors . Proc. Natl Acad. Sci. USA109 ( 22 ), 8746 – 8751 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Liu Y , RimmlerJ , DennisMF , Ashley-KochAE , HauserMA , BeckhamJC . Association of variant rs4790904 in protein kinase C alpha with post-traumatic stress disorder in a U.S. Caucasian and African–American veteran sample . J Depress. Anxiety2 ( 1 ), S4001 ( 2013 ).
   PubMedGoogle Scholar
• Boks MP , RuttenBP , GeuzeEet al. SKA2 methylation is involved in cortisol stress reactivity and predicts the development of post-traumatic stress disorder (PTSD) after military deployment . Neuropsychopharmacology41 ( 5 ), 1350 – 1356 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Belujon P , GraceAA . Regulation of dopamine system responsivity and its adaptive and pathological response to stress . Proc. Biol. Sci.282 ( 1805 ), 20142516 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Nagano-Saito A , DagherA , BooijLet al. Stress-induced dopamine release in human medial prefrontal cortex–18F-fallypride/PET study in healthy volunteers . Synapse67 ( 12 ), 821 – 830 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Pruessner JC , ChampagneF , MeaneyMJ , DagherA . Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride . J. Neurosci.24 ( 11 ), 2825 – 2831 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Lawford BR , BarnesM , SwagellCDet al. DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia . J. Psychopharmacol.27 ( 4 ), 343 – 348 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Davis LL , SurisA , LambertMT , HeimbergC , PettyF . Post-traumatic stress disorder and serotonin: new directions for research and treatment . J. Psychiatry Neurosci.22 ( 5 ), 318 – 326 ( 1997 ).
   PubMed Web of Science ®Google Scholar
• Schneier FR , CampeasR , CarcamoJet al. Combined mirtazapine and SSRI treatment of PTSD: a placebo-controlled trial . Depress. Anxiety32 ( 8 ), 570 – 579 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Wendland JR , MartinBJ , KruseMR , LeschKP , MurphyDL . Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531 . Mol. Psychiatry11 ( 3 ), 224 – 226 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Grabe HJ , SpitzerC , SchwahnCet al. Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to post-traumatic stress disorder in the general population . Am. J. Psychiatry166 ( 8 ), 926 – 933 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Thakur GA , JooberR , BrunetA . Development and persistence of post-traumatic stress disorder and the 5-HTTLPR polymorphism . J. Trauma Stress22 ( 3 ), 240 – 243 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Kim-Cohen J , TurkewitzR . Resilience and measured gene–environment interactions . Dev. Psychopathol.24 ( 4 ), 1297 – 1306 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Wilker S , PfeifferA , KolassaSet al. The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for post-traumatic stress disorder . Transl. Psychiatry4 , e403 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Hammack SE , CheungJ , RhodesKMet al. Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior . Psychoneuroendocrinology34 ( 6 ), 833 – 843 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Stroth N , HolighausY , Ait-AliD , EidenLE . PACAP: a master regulator of neuroendocrine stress circuits and the cellular stress response . Ann. NY Acad. Sci.1220 , 49 – 59 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Niknazar S , NahavandiA , PeyvandiAA , PeyvandiH , AkhtariAS , KarimiM . Comparison of the adulthood chronic stress effect on hippocampal BDNF signaling in male and female rats . Mol. Neurobiol.53 ( 6 ), 4026 – 4033 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Martinotti G , SepedeG , BrunettiMet al. BDNF concentration and impulsiveness level in post-traumatic stress disorder . Psychiatry Res.229 ( 3 ), 814 – 818 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Holbrook TL , GalarneauMR , DyeJL , QuinnK , DoughertyAL . Morphine use after combat injury in Iraq and post-traumatic stress disorder . N. Engl. J. Med.362 ( 2 ), 110 – 117 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Ashley-Koch AE , GarrettME , GibsonJet al. Genome-wide association study of post-traumatic stress disorder in a cohort of Iraq-Afghanistan era veterans . J. Affect. Disord.184 , 225 – 234 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Guffanti G , GaleaS , YanLet al. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women . Psychoneuroendocrinology38 ( 12 ), 3029 – 3038 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kilaru V , IyerSV , AlmliLMet al. Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder . Transl. Psychiatry6 , e820 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Logue MW , BaldwinC , GuffantiGet al. A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus . Mol. Psychiatry18 ( 8 ), 937 – 942 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Nievergelt CM , MaihoferAX , MustapicMet al. Genomic predictors of combat stress vulnerability and resilience in U.S. marines: a genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene . Psychoneuroendocrinology51 , 459 – 471 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Xie P , KranzlerHR , YangC , ZhaoH , FarrerLA , GelernterJ . Genome-wide association study identifies new susceptibility loci for post-traumatic stress disorder . Biol. Psychiatry74 ( 9 ), 656 – 663 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Guffanti G , Ashley-KochAE , RobertsALet al. No association between RORA polymorphisms and PTSD in two independent samples . Mol. Psychiatry19 ( 10 ), 1056 – 1057 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Amstadter AB , SumnerJA , AciernoRet al. Support for association of RORA variant and post traumatic stress symptoms in a population-based study of hurricane exposed adults . Mol. Psychiatry18 ( 11 ), 1148 – 1149 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Miller MW , WolfEJ , LogueMW , BaldwinCT . The retinoid-related orphan receptor alpha (RORA) gene and fear-related psychopathology . J. Affect. Disord.151 ( 2 ), 702 – 708 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Lowe SR , MeyersJL , GaleaSet al. RORA and post-traumatic stress trajectories: main effects and interactions with childhood physical abuse history . Brain Behav.5 ( 4 ), e00323 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Almli LM , StevensJS , SmithAKet al. A genome-wide identified risk variant for PTSD is a methylation quantitative trait locus and confers decreased cortical activation to fearful faces . Am. J. Med. Genet. B Neuropsychiatr. Genet.168b ( 5 ), 327 – 336 ( 2015 ).
   PubMedGoogle Scholar
• Caspi A , SugdenK , MoffittTEet al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene . Science301 ( 5631 ), 386 – 389 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Karg K , BurmeisterM , SheddenK , SenS . The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation . Arch. Gen. Psychiatry68 ( 5 ), 444 – 454 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Risch N , HerrellR , LehnerTet al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis . JAMA301 ( 23 ), 2462 – 2471 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Caspi A , McClayJ , MoffittTEet al. Role of genotype in the cycle of violence in maltreated children . Science297 ( 5582 ), 851 – 854 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Nilsson KW , ComascoE , HodginsS , OrelandL , AslundC . Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: gene–environment interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR [corrected] . Int. J. Neuropsychopharmacol.18 ( 5 ), pii: pyu107 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Januar V , SafferyR , RyanJ . Epigenetics and depressive disorders: a review of current progress and future directions . Int. J. Epidemiol.44 ( 4 ), 1364 – 1387 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Petronis A . Epigenetics as a unifying principle in the aetiology of complex traits and diseases . Nature465 ( 7299 ), 721 – 727 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Boersma GJ , LeeRS , CordnerZAet al. Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats . Epigenetics9 ( 3 ), 437 – 447 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Uchida S , HaraK , KobayashiAet al. Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events . Neuron69 ( 2 ), 359 – 372 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Elliott E , Ezra-NevoG , RegevL , Neufeld-CohenA , ChenA . Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice . Nat. Neurosci.13 ( 11 ), 1351 – 1353 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Kember RL , DempsterEL , LeeTH , SchalkwykLC , MillJ , FernandesC . Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse . Brain Behav.2 ( 4 ), 455 – 467 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Sterrenburg L , GasznerB , BoerrigterJet al. Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat . PLoS ONE6 ( 11 ), e28128 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Weaver IC , CervoniN , ChampagneFAet al. Epigenetic programming by maternal behavior . Nat. Neurosci.7 ( 8 ), 847 – 854 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Uddin M , AielloAE , WildmanDEet al. Epigenetic and immune function profiles associated with post-traumatic stress disorder . Proc. Natl Acad. Sci. USA107 ( 20 ), 9470 – 9475 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Smith AK , ConneelyKN , KilaruVet al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder . Am. J. Med. Genet. B Neuropsychiatr. Genet.156b ( 6 ), 700 – 708 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Von Kanel R , HeppU , KraemerBet al. Evidence for low-grade systemic proinflammatory activity in patients with post-traumatic stress disorder . J. Psychiatr. Res.41 ( 9 ), 744 – 752 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Mehta D , KlengelT , ConneelyKNet al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in post-raumatic stress disorder . Proc. Natl Acad. Sci. USA110 ( 20 ), 8302 – 8307 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Turecki G , MeaneyMJ . Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review . Biol. Psychiatry79 ( 2 ), 87 – 96 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Sadeh N , SpielbergJM , LogueMWet al. SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans . Mol. Psychiatry21 ( 3 ), 357 – 363 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Morris MC , CompasBE , GarberJ . Relations among post-traumatic stress disorder, comorbid major depression, and HPA function: a systematic review and meta-analysis . Clin. Psychol. Rev.32 ( 4 ), 301 – 315 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Roth TL , ZoladzPR , SweattJD , DiamondDM . Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model of post-traumatic stress disorder . J. Psychiatr. Res.45 ( 7 ), 919 – 926 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Keller S , SarchiaponeM , ZarrilliFet al. Increased BDNF promoter methylation in the Wernicke area of suicide subjects . Arch. Gen. Psychiatry67 ( 3 ), 258 – 267 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Rusiecki JA , ByrneC , GaldzickiZet al. PTSD and DNA methylation in select immune function gene promoter regions: a repeated measures case–control study of U.S. military service members . Front. Psychiatry4 , 56 ( 2013 ).
   PubMedGoogle Scholar
• Boks MP , Van MierloHC , RuttenBPet al. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder . Psychoneuroendocrinology51 , 506 – 512 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Horvath S . DNA methylation age of human tissues and cell types . Genome Biol.14 ( 10 ), R115 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Yehuda R , DaskalakisNP , DesarnaudFet al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD . Front. Psychiatry4 , 118 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Sipahi L , WildmanDE , AielloAEet al. Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder . Psychol. Med.44 ( 15 ), 3165 – 3179 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Gluckman PD , HansonMA , CooperC , ThornburgKL . Effect of in utero and early-life conditions on adult health and disease . N. Engl. J. Med.359 ( 1 ), 61 – 73 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Kessler RC , McLaughlinKA , GreenJGet al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys . Br. J. Psychiatry.197 ( 5 ), 378 – 385 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• McGowan PO , SasakiA , D’AlessioACet al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse . Nat. Neurosci.12 ( 3 ), 342 – 348 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Labonte B , SudermanM , MaussionGet al. Genome-wide epigenetic regulation by early-life trauma . Arch. Gen. Psychiatry69 ( 7 ), 722 – 731 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Levenson JM , SweattJD . Epigenetic mechanisms in memory formation . Nat. Rev. Neurosci.6 ( 2 ), 108 – 118 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Oberlander TF , WeinbergJ , PapsdorfM , GrunauR , MisriS , DevlinAM . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses . Epigenetics3 ( 2 ), 97 – 106 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Palma-Gudiel H , Cordova-PalomeraA , EixarchE , DeuschleM , FananasL . Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis . Epigenetics10 ( 10 ), 893 – 902 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Mansell T , VuillerminP , PonsonbyAL , CollierF , SafferyR , RyanJ . Maternal mental well-being during pregnancy and glucocorticoid receptor gene promoter methylation in the neonate . Dev. Psychopathol. doi:10.1017/S09545794160001831 - 10 ( 2016 ) ( Epub ahead of print ).
   Web of Science ®Google Scholar
• Devlin AM , BrainU , AustinJ , OberlanderTF . Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth . PLoS ONE5 ( 8 ), e12201 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Thaler L , GauvinL , JooberRet al. Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder . Prog. Neuropsychopharmacol. Biol. Psychiatry54 , 43 – 49 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Mansell T , NovakovicB , MeyerBet al. The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood . Transl. Psychiatry6 , e765 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Naumova OY , LeeM , KoposovR , SzyfM , DozierM , GrigorenkoEL . Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents . Dev. Psychopathol.24 ( 1 ), 143 – 155 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Essex MJ , BoyceWT , HertzmanCet al. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence . Child Dev.84 ( 1 ), 58 – 75 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Yang BZ , ZhangH , GeWet al. Child abuse and epigenetic mechanisms of disease risk . Am. J. Prev. Med.44 ( 2 ), 101 – 107 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Houtepen LC , VinkersCH , Carrillo-RoaTet al. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans . Nat. Commun.7 , 10967 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Varricchio L , TirelliV , MasselliEet al. The expression of the glucocorticoid receptor in human erythroblasts is uniquely regulated by KIT ligand: implications for stress erythropoiesis . Stem Cells Dev.21 ( 15 ), 2852 – 2865 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Zannas AS , ArlothJ , Carrillo-RoaTet al. Lifetime stress accelerates epigenetic aging in an urban, African–American cohort: relevance of glucocorticoid signaling . Genome Biol.16 , 266 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Van Der Knaap LJ , RieseH , HudziakJJet al. Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study . Transl. Psychiatry4 , e381 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Yehuda R , DaskalakisNP , BiererLMet al. Holocaust exposure induced intergenerational effects on FKBP5 methylation . Biol. Psychiatry80 ( 5 ), 372 – 380 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Cichon S , CraddockN , DalyMet al. Genomewide association studies: history, rationale, and prospects for psychiatric disorders . Am. J. Psychiatry166 ( 5 ), 540 – 556 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Logue MW , AmstadterAB , BakerDGet al. The psychiatric genomics consortium post-traumatic stress disorder workgroup: post-traumatic stress disorder enters the age of large-scale genomic collaboration . Neuropsychopharmacology40 ( 10 ), 2287 – 2297 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Abel T , ZukinRS . Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders . Curr. Opin. Pharmacol.8 ( 1 ), 57 – 64 ( 2008 ).
   PubMed Web of Science ®Google Scholar