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Genetic associations with resilience to potentially traumatic events and vantage sensitivity to social support

      Highlights

      • Resilience responses to potentially traumatic events (PTEs) are influenced by many factors, including genetics.
      • In this study, the G/G genotype of rs1800795 in Interleukin 6 (IL6) gene was associated with resilience to PTEs.
      • Met/Met of rs4680 in Catechol-O-MethylTransferase (COMT) gene was associated with greater sensitivity to social support.
      • Resilience needs to be viewed holistically from not only psychosocial but also genetic factors as well.

      Abstract

      Introduction

      Stress responses and mental health outcomes greatly vary when individuals are exposed to potentially traumatic events (PTEs). The Differential Susceptibility Model (DSM) (Pluess, 2015) suggests individual differences in stress responses are influenced by gene-environment interactions, with genes conferring reactivity. While individuals can be resilient (or vulnerable) to PTEs, they can also have vantage sensitivity (or resistance) to social support. This study examined whether selected genotypes moderated the effect of PTEs and social support on mental health.

      Methods

      This cross-sectional candidate gene study included 450 college students (M age = 20.4, 79.3 % women) who provided buccal cells for genotyping and completed measures of psychosocial variables. DNA was genotyped for 12 genetic variants.

      Results

      Hierarchical regression revealed that the Mental Health Inventory (MHI) was associated with the Trauma History Questionnaire (THQ), rs1800795 in IL-6, and THQ × rs1800795 [R2 = 0.10, F(3, 418) = 15.68, p < .01]. The MHI was associated with the Social Support Survey (SSS), rs4680 in COMT, and SSS × rs4680 [R2 = 0.24, F(3, 429) = 44.19, p < .01]. Only THQ and SSS survived multiple testing corrections.

      Discussion

      Findings partially support the DSM that the G/G genotype of rs1800795 in IL-6 is associated with resilience to PTEs, and the Met/Met genotype of rs4680 in COMT is associated with vantage sensitivity to social support. Limitations include cross-sectional design, limited PTE measurement, small convenience sample, and noncorrection for multiple significance test. Clinicians need to view resilience holistically and understand resilience is associated with psychosocial and genetic factors.

      Keywords

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      References

        • American Psychiatric Association
        Diagnostic and statistical manual of mental disorders.
        5th ed. American Psychiatric Association, 2013
        • Assary E.
        • Vincent J.P.
        • Keers R.
        • Pluess M.
        Gene-environment interaction and psychiatric disorders: Review and future directions.
        Seminars in Cell & Developmental Biology. 2018; 77: 133-143https://doi.org/10.1016/j.semcdb.2017.10.016
        • Bakermans-Kranenburg M.J.
        • van Ijzendoorn M.H.
        A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans.
        Psychiatric Genetics. 2014; 24: 45-51https://doi.org/10.1097/YPG.0b013e3283643684
        • Belsky J.
        • Pluess M.
        Beyond diathesis stress: Differential susceptibility to environmental influences.
        Psychological Bulletin. 2009; 135: 885-908https://doi.org/10.1037/a0017376
        • Benjamini Y.
        • Drai D.
        • Elmer G.
        • Kafkafi N.
        • Golani I.
        Controlling the false discovery rate in behavior genetics research.
        Behavioural Brain Research. 2001; 125: 279-284https://doi.org/10.1016/S0166-4328(01)00297-2
        • Benjet C.
        • Bromet E.
        • Karam E.G.
        • Kessler R.C.
        • McLaughlin K.A.
        • Ruscio A.M.
        • Shahly V.
        • Stein D.J.
        • Petukhova M.
        • Hill E.
        • Alonso J.
        • Atwoli L.
        • Bunting B.
        • Bruffaerts R.
        • Caldas-de-Almeida J.M.
        • de Girolamo G.
        • Florescu S.
        • Gureje O.
        • Huang Y.
        • Koenen K.C.
        The epidemiology of traumatic event exposure worldwide: Results from the world mental health survey consortium.
        Psychological Medicine. 2016; 46: 327-343https://doi.org/10.1017/S0033291715001981
        • Beste C.
        • Baune B.T.
        • Falkenstein M.
        • Konrad C.
        Variations in the TNF-alpha gene (TNF-alpha -308G–>A) affect attention and action selection mechanisms in a dissociated fashion.
        Journal of Neurophysiology. 2010; 104: 2523-2531https://doi.org/10.1152/jn.00561.2010
        • Binder E.B.
        • Bradley R.G.
        • Liu W.
        • Epstein M.P.
        • Deveau T.C.
        • Mercer K.B.
        • Tang Y.
        • Gillespie C.F.
        • Heim C.M.
        • Nemeroff C.B.
        • Schwartz A.C.
        • Cubells J.F.
        • Ressler K.J.
        Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults.
        JAMA. 2008; 299: 1291-1305https://doi.org/10.1001/jama.299.11.1291
        • Bonanno G.A.
        • Diminich E.D.
        Annual research review: Positive adjustment to adversity–trajectories of minimal-impact resilience and emergent resilience.
        J Child Psychol Psychiatry. 2013; 54: 378-401https://doi.org/10.1111/jcpp.12021
        • Bonanno G.A.
        • Mancini A.D.
        The human capacity to thrive in the face of potential trauma.
        Pediatrics. 2008; 121: 369-375https://doi.org/10.1542/peds.2007-1648
        • Caspi A.
        • Sugden K.
        • Moffitt T.E.
        • Taylor A.
        • Craig I.W.
        • Harrington H.
        • McClay J.
        • Mill J.
        • Martin J.
        • Braithwaite A.
        • Poulton R.
        Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene.
        Science. 2003; 301: 386-389https://doi.org/10.1126/science.1083968
        • Chen J.
        • Lipska B.K.
        • Halim N.
        • Ma Q.D.
        • Matsumoto M.
        • Melhem S.
        • Kolachana B.S.
        • Hyde T.M.
        • Herman M.M.
        • Apud J.
        • Egan M.F.
        • Kleinman J.E.
        • Weinberger D.R.
        Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain.
        American Journal of Human Genetics. 2004; 75: 807-821https://doi.org/10.1086/425589
        • Cicchetti D.
        • Rogosch F.A.
        Gene x environment interaction and resilience: Effects of child maltreatment and serotonin, corticotropin releasing hormone, dopamine, and oxytocin genes.
        Development and Psychopathology. 2012; 24: 411-427https://doi.org/10.1017/S0954579412000077
        • Cole S.W.
        • Arevalo J.M.
        • Takahashi R.
        • Sloan E.K.
        • Lutgendorf S.K.
        • Sood A.K.
        • Sheridan J.F.
        • Seeman T.E.
        Computational identification of gene-social environment interaction at the human IL6 locus.
        Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 5681-5686https://doi.org/10.1073/pnas.0911515107
        • Cole S.W.
        • Arevalo J.M.
        • Manu K.
        • Telzer E.H.
        • Kiang L.
        • Bower J.E.
        • Irwin M.R.
        • Fuligni A.J.
        Antagonistic pleiotropy at the human IL6 promoter confers genetic resilience to the pro-inflammatory effects of adverse social conditions in adolescence.
        Developmental Psychology. 2011; 47: 1173-1180https://doi.org/10.1037/a0023871
        • Conley A.H.
        • Overstreet C.M.
        • Hawn S.E.
        • Kendler K.S.
        • Dick D.M.
        • Amstadter A.B.
        Prevalence and predictors of sexual assault among a college sample.
        Journal of American College Health. 2017; 65: 41-49https://doi.org/10.1080/07448481.2016.1235578
        • Corral-Frias N.S.
        • Pizzagalli D.A.
        • Carre J.M.
        • Michalski L.J.
        • Nikolova Y.S.
        • Perlis R.H.
        • Fagerness J.
        • Lee M.R.
        • Conley E.D.
        • Lancaster T.M.
        • Haddad S.
        • Wolf A.
        • Smoller J.W.
        • Hariri A.R.
        • Bogdan R.
        COMT Val(158) met genotype is associated with reward learning: A replication study and meta-analysis.
        Genes, Brain, and Behavior. 2016; 15: 503-513https://doi.org/10.1111/gbb.12296
        • de Villiers B.
        • Lionetti F.
        • Pluess M.
        Vantage sensitivity: A framework for individual differences in response to psychological intervention.
        Social Psychiatry and Psychiatric Epidemiology. 2018; https://doi.org/10.1007/s00127-017-1471-0
        • Dedic N.
        • Pohlmann M.L.
        • Richter J.S.
        • Mehta D.
        • Czamara D.
        • Metzger M.W.
        • Dine J.
        • Bedenk B.T.
        • Hartmann J.
        • Wagner K.V.
        • Jurik A.
        • Almli L.M.
        • Lori A.
        • Moosmang S.
        • Hofmann F.
        • Wotjak C.T.
        • Rammes G.
        • Eder M.
        • Chen A.
        • Deussing J.M.
        Cross-disorder risk gene CACNA1C differentially modulates susceptibility to psychiatric disorders during development and adulthood.
        Molecular Psychiatry. 2018; 23: 533-543https://doi.org/10.1038/mp.2017.133
        • Dick D.M.
        • Agrawal A.
        • Keller M.C.
        • Adkins A.
        • Aliev F.
        • Monroe S.
        • Hewitt J.K.
        • Kendler K.S.
        • Sher K.J.
        Candidate gene-environment interaction research: Reflections and recommendations.
        Perspectives on Psychological Science. 2015; 10: 37-59https://doi.org/10.1177/1745691614556682
        • Dunn E.C.
        • Solovieff N.
        • Lowe S.R.
        • Gallagher P.J.
        • Chaponis J.
        • Rosand J.
        • Koenen K.C.
        • Waters M.C.
        • Rhodes J.E.
        • Smoller J.W.
        Interaction between genetic variants and exposure to hurricane Katrina on post-traumatic stress and post-traumatic growth: A prospective analysis of low income adults.
        Journal of Affective Disorders. 2014; 152–154: 243-249https://doi.org/10.1016/j.jad.2013.09.018
        • Ebrahimi N.
        • Bilgili D.
        A new method of testing for Hardy-Weinberg equilibrium and ordering populations.
        Journal of Genetics. 2007; 86: 1-7
        • Elbau I.G.
        • Cruceanu C.
        • Binder E.B.
        Genetics of resilience: Gene-by-environment interaction studies as a tool to dissect mechanisms of resilience.
        Biological Psychiatry. 2019; 86: 433-442https://doi.org/10.1016/j.biopsych.2019.04.025
        • Ellis B.J.
        • Boyce W.T.
        • Belsky J.
        • Bakermans-Kranenburg M.J.
        • van Ijzendoorn M.H.
        Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory.
        Development and Psychopathology. 2011; 23: 7-28https://doi.org/10.1017/S0954579410000611
        • El-Tahan R.R.
        • Ghoneim A.M.
        • El-Mashad N.
        TNF-alpha gene polymorphisms and expression.
        Springerplus. 2016; 5: 1508https://doi.org/10.1186/s40064-016-3197-y
        • Feder A.
        • Nestler E.J.
        • Charney D.S.
        Psychobiology and molecular genetics of resilience.
        Nature Reviews Neuroscience. 2009; 10: 446-457https://doi.org/10.1038/nrn2649
        • Fishman D.
        • Faulds G.
        • Jeffery R.
        • Mohamed-Ali V.
        • Yudkin J.S.
        • Humphries S.
        • Woo P.
        The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.
        The Journal of Clinical Investigation. 1998; 102: 1369-1376https://doi.org/10.1172/JCI2629
        • Frazier P.
        • Anders S.
        • Perera S.
        • Tomich P.
        • Tennen H.
        • Park C.
        • Tashiro T.
        Traumatic events among undergraduate students: Prevalence and associated symptoms.
        Journal of Counseling Psychology. 2009; 56: 450-460https://doi.org/10.1037/a0016412
        • Goldstein R.B.
        • Smith S.M.
        • Chou S.P.
        • Saha T.D.
        • Jung J.
        • Zhang H.
        • Pickering R.P.
        • Ruan W.J.
        • Huang B.
        • Grant B.F.
        The epidemiology of DSM-5 posttraumatic stress disorder in the United States: Results from the National Epidemiologic Survey on alcohol and related conditions-III.
        Social Psychiatry and Psychiatric Epidemiology. 2016; 51: 1137-1148https://doi.org/10.1007/s00127-016-1208-5
        • Gong P.
        • Fan H.
        • Liu J.
        • Yang X.
        • Zhang K.
        • Zhou X.
        Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis.
        Psychoneuroendocrinology. 2017; 80: 131-136https://doi.org/10.1016/j.psyneuen.2017.03.005
        • Greisenegger S.
        • Endler G.
        • Haering D.
        • Schillinger M.
        • Lang W.
        • Lalouschek W.
        • Mannhalter C.
        The (-174) G/C polymorphism in the interleukin-6 gene is associated with the severity of acute cerebrovascular events.
        Thrombosis Research. 2003; 110: 181-186https://doi.org/10.1016/s0049-3848(03)00376-1
        • Hajeer A.H.
        • Hutchinson I.V.
        Influence of TNFalpha gene polymorphisms on TNFalpha production and disease.
        Human Immunology. 2001; 62: 1191-1199
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • Payne J.
        • Gonzalez N.
        • Conde J.G.
        Research electronic data capture (REDCap): A metadata-driven methodology and workflow process for providing translational research informatics support.
        Journal of Biomedical Informatics. 2009; 42: 377-381https://doi.org/10.1016/j.jbi.2008.08.010
        • Hawn S.E.
        • Sheerin C.M.
        • Lind M.J.
        • Hicks T.A.
        • Marraccini M.E.
        • Bountress K.
        • Bacanu S.A.
        • Nugent N.R.
        • Amstadter A.B.
        GxE effects of FKBP5 and traumatic life events on PTSD: A meta-analysis.
        Journal of Affective Disorders. 2019; 243: 455-462https://doi.org/10.1016/j.jad.2018.09.058
        • Hooper L.M.
        • Stockton P.
        • Krupnick J.L.
        • Green B.L.
        Development, use, and psychometric properties of the trauma history questionnaire.
        Journal of Loss and Trauma. 2011; 16: 258-283https://doi.org/10.1080/15325024.2011.572035
        • Hu X.Z.
        • Lipsky R.H.
        • Zhu G.
        • Akhtar L.A.
        • Taubman J.
        • Greenberg B.D.
        • Xu K.
        • Arnold P.D.
        • Richter M.A.
        • Kennedy J.L.
        • Murphy D.L.
        • Goldman D.
        Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder.
        American Journal of Human Genetics. 2006; 78: 815-826https://doi.org/10.1086/503850
        • Hunter J.E.
        • Leslie M.
        • Novak G.
        • Hamilton D.
        • Shubeck L.
        • Charen K.
        • Abramowitz A.
        • Epstein M.P.
        • Lori A.
        • Binder E.
        • Cubells J.F.
        • Sherman S.L.
        Depression and anxiety symptoms among women who carry the FMR1 premutation: Impact of raising a child with fragile X syndrome is moderated by CRHR1 polymorphisms.
        American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2012; 159B: 549-559https://doi.org/10.1002/ajmg.b.32061
        • Illig T.
        • Bongardt F.
        • Schopfer A.
        • Muller-Scholze S.
        • Rathmann W.
        • Koenig W.
        • Thorand B.
        • Vollmert C.
        • Holle R.
        • Kolb H.
        • Herder C.
        • Kooperative Gesundheitsforschung im Raum Augsburg/Cooperative Research in the Region of A.
        Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes.
        The Journal of Clinical Endocrinology and Metabolism. 2004; 89: 5053-5058https://doi.org/10.1210/jc.2004-0355
        • Kabir Z.D.
        • Martinez-Rivera A.
        • Rajadhyaksha A.M.
        From gene to behavior: L-type calcium channel mechanisms underlying neuropsychiatric symptoms.
        Neurotherapeutics. 2017; 14: 588-613https://doi.org/10.1007/s13311-017-0532-0
        • Kessler R.C.
        • Sonnega A.
        • Bromet E.
        • Hughes M.
        • Nelson C.B.
        Posttraumatic stress disorder in the National Comorbidity Survey.
        Archives of General Psychiatry. 1995; 52: 1048-1060
        • Koenen K.C.
        • Amstadter A.B.
        • Ruggiero K.J.
        • Acierno R.
        • Galea S.
        • Kilpatrick D.G.
        • Gelernter J.
        RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults.
        Depression and Anxiety. 2009; 26: 309-315https://doi.org/10.1002/da.20528
        • Koenen K.C.
        • Ratanatharathorn A.
        • Ng L.
        • McLaughlin K.A.
        • Bromet E.J.
        • Stein D.J.
        • Karam E.G.
        • Meron Ruscio A.
        • Benjet C.
        • Scott K.
        • Atwoli L.
        • Petukhova M.
        • Lim C.C.W.
        • Aguilar-Gaxiola S.
        • Al-Hamzawi A.
        • Alonso J.
        • Bunting B.
        • Ciutan M.
        • de Girolamo G.
        • Kessler R.C.
        Posttraumatic stress disorder in the world mental health surveys.
        Psychological Medicine. 2017; 47: 2260-2274https://doi.org/10.1017/S0033291717000708
        • Lesch K.P.
        • Bengel D.
        • Heils A.
        • Sabol S.Z.
        • Greenberg B.D.
        • Petri S.
        • Benjamin J.
        • Muller C.R.
        • Hamer D.H.
        • Murphy D.L.
        Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
        Science. 1996; 274 (http://science.sciencemag.org/content/274/5292/1527.long): 1527-1531
        • Li J.
        • Zhao Y.
        • Li R.
        • Broster L.S.
        • Zhou C.
        • Yang S.
        Association of oxytocin receptor gene (OXTR) rs53576 polymorphism with sociality: A meta-analysis.
        PLoS One. 2015; 10e0131820https://doi.org/10.1371/journal.pone.0131820
        • Li L.
        • Bao Y.
        • He S.
        • Wang G.
        • Guan Y.
        • Ma D.
        • Wang P.
        • Huang X.
        • Tao S.
        • Zhang D.
        • Liu Q.
        • Wang Y.
        • Yang J.
        The association between genetic variants in the dopaminergic system and posttraumatic stress disorder: A meta-analysis.
        Medicine (Baltimore). 2016; 95e3074https://doi.org/10.1097/MD.0000000000003074
        • Lipsky R.H.
        • Marini A.M.
        Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity.
        Annals of the New York Academy of Sciences. 2007; 1122: 130-143https://doi.org/10.1196/annals.1403.009
        • Luthar S.S.
        • Cicchetti D.
        • Becker B.
        The construct of resilience: A critical evaluation and guidelines for future work.
        Child Development. 2000; 71: 543-562
        • Marioni R.E.
        • Deary I.J.
        • Murray G.D.
        • Fowkes F.G.
        • Price J.F.
        Associations between polymorphisms in five inflammation-related genes and cognitive ability in older persons.
        Genes, Brain, and Behavior. 2010; 9: 348-352https://doi.org/10.1111/j.1601-183X.2010.00565.x
        • Masten A.S.
        Resilience in children threatened by extreme adversity: Frameworks for research, practice, and translational synergy.
        Development and Psychopathology. 2011; 23: 493-506https://doi.org/10.1017/S0954579411000198
        • Mooijaart S.P.
        • Sattar N.
        • Trompet S.
        • Lucke J.
        • Stott D.J.
        • Ford I.
        • Jukema J.W.
        • Westendorp R.G.
        • de Craen A.J.
        • Group P.S.
        Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study.
        Journal of Internal Medicine. 2013; 274: 77-85https://doi.org/10.1111/joim.12052
        • Morris K.A.
        • Grace S.A.
        • Woods W.
        • Dean B.
        • Rossell S.L.
        The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review.
        European Journal of Neuroscience. 2020; : n/a(n/a)https://doi.org/10.1111/ejn.14748
        • National Center for Biotechnology Information
        CRHR1 corticotropin releasing hormone receptor 1 [Homo sapiens (human)].
        • National Center for Biotechnology Information
        OXTR oxytocin receptor [Homo sapiens (human)].
        • National Center for Biotechnology Information
        RGS2 regulator of G protein signaling 2 [Homo sapiens (human)].
        • Nederhof E.
        • Bouma E.M.
        • Riese H.
        • Laceulle O.M.
        • Ormel J.
        • Oldehinkel A.J.
        Evidence for plasticity genotypes in a gene-gene-environment interaction: The TRAILS study.
        Genes, Brain and Behavior. 2010; 9: 968-973https://doi.org/10.1111/j.1601-183X.2010.00637.x
        • Niitsu K.
        Genetic influence on psychological resilience to potentially traumatic events.
        (Doctoral dissertation)2017
        • Niitsu K.
        • Houfek J.F.
        • Barron C.R.
        • Stoltenberg S.F.
        • Kupzyk K.A.
        • Rice M.J.
        A concept analysis of resilience integrating genetics.
        Issues in Mental Health Nursing. 2017; 38: 896-906https://doi.org/10.1080/01612840.2017.1350225
        • Niitsu K.
        • Rice M.J.
        • Houfek J.F.
        • Stoltenberg S.F.
        • Kupzyk K.A.
        • Barron C.R.
        A systematic review of genetic influence on psychological resilience.
        Biological Research for Nursing. 2019; 21: 61-71https://doi.org/10.1177/1099800418800396
        • Osorio C.
        • Probert T.
        • Jones E.
        • Young A.H.
        • Robbins I.
        Adapting to stress: Understanding the neurobiology of resilience.
        Behavioral Medicine. 2017; 43: 307-322https://doi.org/10.1080/08964289.2016.1170661
        • Parsey R.V.
        • Hastings R.S.
        • Oquendo M.A.
        • Hu X.
        • Goldman D.
        • Huang Y.Y.
        • Simpson N.
        • Arcement J.
        • Huang Y.
        • Ogden R.T.
        • Van Heertum R.L.
        • Arango V.
        • Mann J.J.
        Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain.
        The American Journal of Psychiatry. 2006; 163: 48-51https://doi.org/10.1176/appi.ajp.163.1.48
        • Pluess M.
        Individual differences in environmental sensitivity.
        Child Development Perspectives. 2015; 9: 138-143https://doi.org/10.1111/cdep.12120
        • Pluess M.
        Vantage sensitivity: Environmental sensitivity to positive experiences as a function of genetic differences.
        Journal of Personality. 2017; 85: 38-50https://doi.org/10.1111/jopy.12218
        • Rodriguez S.
        • Gaunt T.R.
        • Day I.N.
        Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies.
        American Journal of Epidemiology. 2009; 169: 505-514https://doi.org/10.1093/aje/kwn359
        • Rogers J.
        • Raveendran M.
        • Fawcett G.L.
        • Fox A.S.
        • Shelton S.E.
        • Oler J.A.
        • Cheverud J.
        • Muzny D.M.
        • Gibbs R.A.
        • Davidson R.J.
        • Kalin N.H.
        CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression.
        Molecular Psychiatry. 2013; 18: 700-707https://doi.org/10.1038/mp.2012.152
        • Rutten B.P.
        • Hammels C.
        • Geschwind N.
        • Menne-Lothmann C.
        • Pishva E.
        • Schruers K.
        • van den Hove D.
        • Kenis G.
        • van Os J.
        • Wichers M.
        Resilience in mental health: Linking psychological and neurobiological perspectives.
        Acta Psychiatrica Scandinavica. 2013; 128: 3-20https://doi.org/10.1111/acps.12095
        • Rutter M.
        Resilience as a dynamic concept.
        Development and Psychopathology. 2012; 24: 335-344https://doi.org/10.1017/S0954579412000028
        • Ryan J.
        • Pilkington L.
        • Neuhaus K.
        • Ritchie K.
        • Ancelin M.L.
        • Saffery R.
        Investigating the epigenetic profile of the inflammatory gene IL-6 in late-life depression.
        BMC Psychiatry. 2017; 17: 354https://doi.org/10.1186/s12888-017-1515-8
        • Schultze-Florey C.R.
        • Martinez-Maza O.
        • Magpantay L.
        • Breen E.C.
        • Irwin M.R.
        • Gundel H.
        • O'Connor M.F.
        When grief makes you sick: Bereavement induced systemic inflammation is a question of genotype.
        Brain, Behavior, and Immunity. 2012; 26: 1066-1071https://doi.org/10.1016/j.bbi.2012.06.009
        • Sherbourne C.D.
        • Stewart A.L.
        The MOS social support survey.
        Social Science & Medicine. 1991; 32: 705-714
        • Shields G.S.
        • Moons W.G.
        • Slavich G.M.
        Inflammation, self-regulation, and health: An immunologic model of self-regulatory failure.
        Perspectives on Psychological Science. 2017; 12: 588-612https://doi.org/10.1177/1745691616689091
        • Smith K.J.
        • Au B.
        • Ollis L.
        • Schmitz N.
        The association between C-reactive protein, Interleukin-6 and depression among older adults in the community: A systematic review and meta-analysis.
        Experimental Gerontology. 2018; 102: 109-132https://doi.org/10.1016/j.exger.2017.12.005
        • Southwick S.M.
        • Litz B.T.
        • Charney D.
        • Friedman M.J.
        Resilience and mental health: Challenges across the lifespan.
        Cambridge University Press, 2011
        • Southwick S.M.
        • Bonanno G.A.
        • Masten A.S.
        • Panter-Brick C.
        • Yehuda R.
        Resilience definitions, theory, and challenges: Interdisciplinary perspectives.
        European Journal of Psychotraumatology. 2014; 5https://doi.org/10.3402/ejpt.v5.25338
        • Stein M.B.
        • Campbell-Sills L.
        • Gelernter J.
        Genetic variation in 5HTTLPR is associated with emotional resilience.
        American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2009; 150B: 900-906https://doi.org/10.1002/ajmg.b.30916
        • Strohmaier J.
        • Amelang M.
        • Hothorn L.A.
        • Witt S.H.
        • Nieratschker V.
        • Gerhard D.
        • Meier S.
        • Wust S.
        • Frank J.
        • Loerbroks A.
        • Rietschel M.
        • Sturmer T.
        • Schulze T.G.
        The psychiatric vulnerability gene CACNA1C and its sex-specific relationship with personality traits, resilience factors and depressive symptoms in the general population.
        Molecular Psychiatry. 2013; 18: 607-613https://doi.org/10.1038/mp.2012.53
        • Sulik M.J.
        • Eisenberg N.
        • Spinrad T.L.
        • Lemery-Chalfant K.
        • Swann G.
        • Silva K.M.
        • Reiser M.
        • Stover D.A.
        • Verrelli B.C.
        Interactions among catechol-O-methyltransferase genotype, parenting, and sex predict children's internalizing symptoms and inhibitory control: Evidence for differential susceptibility.
        Development and Psychopathology. 2015; 27: 709-723https://doi.org/10.1017/S0954579414000807
        • Tartter M.
        • Hammen C.
        • Bower J.E.
        • Brennan P.A.
        • Cole S.
        Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1beta in youth.
        Brain, Behavior, and Immunity. 2015; 46: 104-111https://doi.org/10.1016/j.bbi.2015.01.003
        • U.S. National Library of Medicine
        CACNA1C gene.
        • U.S. National Library of Medicine
        COMT gene.
        • U.S. National Library of Medicine
        DRD2 gene.
        • U.S. National Library of Medicine
        DRD4 gene.
        • U.S. National Library of Medicine
        FKBP5 gene.
        • U.S. National Library of Medicine
        IL6 gene.
        • U.S. National Library of Medicine
        Reference SNP report: rs6265.
        • Valkanova V.
        • Ebmeier K.P.
        • Allan C.L.
        CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies.
        Journal of Affective Disorders. 2013; 150: 736-744https://doi.org/10.1016/j.jad.2013.06.004
        • van Winkel M.
        • Peeters F.
        • van Winkel R.
        • Kenis G.
        • Collip D.
        • Geschwind N.
        • Jacobs N.
        • Derom C.
        • Thiery E.
        • van Os J.
        • Myin-Germeys I.
        • Wichers M.
        Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: Replication and extension of a gene-environment interaction.
        European Neuropsychopharmacology. 2014; 24: 930-938https://doi.org/10.1016/j.euroneuro.2014.02.005
        • Veit C.T.
        • Ware Jr., J.E.
        The structure of psychological distress and well-being in general populations.
        Journal of Consulting and Clinical Psychology. 1983; 51: 730-742
        • Walker F.R.
        • Pfingst K.
        • Carnevali L.
        • Sgoifo A.
        • Nalivaiko E.
        In the search for integrative biomarker of resilience to psychological stress.
        Neuroscience and Biobehavioral Reviews. 2017; 74: 310-320https://doi.org/10.1016/j.neubiorev.2016.05.003
        • Wang Q.
        • Shelton R.C.
        • Dwivedi Y.
        Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.
        Journal of Affective Disorders. 2018; 225: 422-428https://doi.org/10.1016/j.jad.2017.08.066
        • Wendland J.R.
        • Martin B.J.
        • Kruse M.R.
        • Lesch K.P.
        • Murphy D.L.
        Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531.
        Molecular Psychiatry. 2006; 11: 224-226https://doi.org/10.1038/sj.mp.4001789
        • Wilson A.G.
        • Symons J.A.
        • McDowell T.L.
        • McDevitt H.O.
        • Duff G.W.
        Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.
        Proceedings of the National Academy of Sciences of the United States of America. 1997; 94: 3195-3199
        • Wu G.
        • Feder A.
        • Cohen H.
        • Kim J.J.
        • Calderon S.
        • Charney D.S.
        • Mathe A.A.
        Understanding resilience.
        Frontiers in Behavioral Neuroscience. 2013; 7: 10https://doi.org/10.3389/fnbeh.2013.00010
        • Yehuda R.
        • Hoge C.W.
        • McFarlane A.C.
        • Vermetten E.
        • Lanius R.A.
        • Nievergelt C.M.
        • Hobfoll S.E.
        • Koenen K.C.
        • Neylan T.C.
        • Hyman S.E.
        Post-traumatic stress disorder.
        Nature Reviews Disease Primers. 2015; 1: 15057https://doi.org/10.1038/nrdp.2015.57
        • Zhu D.
        • Yin J.
        • Liang C.
        • Luo X.
        • Lv D.
        • Dai Z.
        • Xiong S.
        • Fu J.
        • Li Y.
        • Lin J.
        • Lin Z.
        • Wang Y.
        • Ma G.
        CACNA1C (rs1006737) may be a susceptibility gene for schizophrenia: An updated meta-analysis.
        Brain and Behavior: A Cognitive Neuroscience Perspective. 2019; 9e01292https://doi.org/10.1002/brb3.1292