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Gene Environment Interplays: Why PTSD Makes a Good Case for Gene–Environment Interaction Studies and How Adding a Developmental Approach Can Help

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Comprehensive Guide to Post-Traumatic Stress Disorder

Abstract

This chapter provides a review of gene–environment interaction (GxE) research in the etiology of post-traumatic stress disorder (PTSD). Gene–environment interaction is a form of causal interplay, whereby genetic effects are moderated by environmental factors.

It will be outlined why GxE presents both unique opportunities and challenges for the comprehension of PTSD, why GxE is controversial, and how it is investigated.

A better knowledge of GxE is at the basis of individual vulnerability and resilience to PTSD; it can inform primary prevention and pave the way toward individually tailored therapies.

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Abbreviations

5-HTTLPR:

Serotonin transporter-linked polymorphic region

ADCYAP1:

Adenylate cyclase activating polypeptide 1 (pituitary)

FKBP5:

FK506 binding protein 5

HPA:

Hypothalamo–pituitary–adrenal

PTSD:

Post-traumatic stress disorder

rGE:

Gene–environment correlation

Rgs2:

Regulator of G-protein signaling 2

rs:

Reference SNP

s:

Short

SLC6A4:

Solute carrier family 6 (neurotransmitter transporter, sertonin) member 4

SNP:

Single nucleotide polymorphism

References

  • Adams RE, Boscarino JA. Predictors of PTSD and delayed PTSD after disaster: the impact of exposure and psychosocial resources. J Nerv Ment Dis. 2006;194:485–93.

    Article  PubMed Central  PubMed  Google Scholar 

  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.

    Google Scholar 

  • Amstadter AB, Koenen KC, Ruggiero KJ, et al. Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. J Anxiety Disord. 2009a;23:369–73.

    Article  PubMed Central  PubMed  Google Scholar 

  • Amstadter AB, Nugent NR, Koenen KC, et al. Association between COMT, PTSD, and increased smoking following hurricane exposure in an epidemiologic sample. Psychiatry. 2009b;72:360–9.

    Article  PubMed Central  PubMed  Google Scholar 

  • Barr CS, Newman TK, Schwandt M, et al. Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. Proc Natl Acad Sci U S A. 2004;101:12358–63.

    Article  PubMed Central  PubMed  Google Scholar 

  • Battaglia M. Is behavioral genetics ‘too-big-to-know’science? Behav Brain Sci. 2012;35:360.

    Article  PubMed  Google Scholar 

  • Battaglia M. In review Gene–Environment interaction in panic disorder and posttraumatic stress disorder. Can J Psychiatry. 2013;58:69–75.

    PubMed  Google Scholar 

  • Bennett P, Owen RL, Koutsakis S, Bisson J. Personality, social context and cognitive predictors of post-traumatic stress disorder in myocardial infarction patients. Psychol Health. 2002;17:489–500.

    Article  Google Scholar 

  • Binder EB, Bradley RG, Liu W, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299:1291–305.

    Article  PubMed Central  PubMed  Google Scholar 

  • Breslau N, Lucia VC, Alvarado GF. Intelligence and other predisposing factors in exposure to trauma and posttraumatic stress disorder: a follow-up study at age 17 years. Arch Gen Psychiatry. 2006;63:1238–45.

    Article  PubMed  Google Scholar 

  • Brewin CR, Andrews B, Valentine JD. Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol. 2000;68:748.

    Article  PubMed  Google Scholar 

  • Brosschot JF, Gerin W, Thayer JF. The perseverative cognition hypothesis: a review of worry, prolonged stress-related physiological activation, and health. J Psychosom Res. 2006;60:113–24.

    Article  PubMed  Google Scholar 

  • Caffo E, Forresi B, Strik Lievers L. Impact, psychological sequelae and management of trauma affecting children and adolescents. Curr Opin Psychiatry. 2005;18:422–8.

    Article  PubMed  Google Scholar 

  • Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry. 2010;167:509–27.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cornelis MC, Nugent NR, Amstadter AB, Koenen KC. Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies. Curr Psychiatry Rep. 2010;12:313–26.

    Article  PubMed Central  PubMed  Google Scholar 

  • Costello EJ, Eaves L, Sullivan P, Kennedy M, Conway K, Adkins DE, Angold A, Clark SL, Erkanli A, McClay JL, Copeland W, Maes HH, Liu Y, Patkar AA, Silberg J, van den Oord E. Genes, environments, and developmental research: methods for a multi-site study of early substance abuse. Twin Res Hum Genet. 2013;16:505–15.

    Article  PubMed Central  PubMed  Google Scholar 

  • D’Onofrio BM, Lahey BB, Turkheimer E, Lichtenstein P. Critical need for family-based, quasi-experimental designs in integrating genetic and social science research. Am J Public Health. 2013;103:S46–55.

    Article  PubMed Central  PubMed  Google Scholar 

  • Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012;106:29–39.

    Article  PubMed  Google Scholar 

  • Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci U S A. 2007;104:1319–24.

    Article  PubMed Central  PubMed  Google Scholar 

  • De Bellis MD, Keshavan MS, Shifflett H, et al. Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study. Biol Psychiatry. 2002;52:1066–78.

    Article  PubMed  Google Scholar 

  • Evans GW, Schamberg MA. Childhood poverty, chronic stress, and adult working memory. Proc Natl Acad Sci U S A. 2009;106:6545–9.

    Article  PubMed Central  PubMed  Google Scholar 

  • Gillespie CF, Phifer J, Bradley B, Ressler KJ. Risk and resilience: genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26:984–92.

    Article  PubMed Central  PubMed  Google Scholar 

  • Grabe H, Spitzer C, Schwahn C, et al. Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am J Psychiatry. 2009;166:926–33.

    Article  PubMed  Google Scholar 

  • Haglund ME, Nestadt P, Cooper N, Southwick S, Charney D. Psychobiological mechanisms of resilience: relevance to prevention and treatment of stress-related psychopathology. Dev Psychopathol. 2007;19:889–920.

    Article  PubMed  Google Scholar 

  • Kaplow JB, Widom CS. Age of onset of child maltreatment predicts long-term mental health outcomes. J Abnorm Psychol. 2007;116:176.

    Article  PubMed  Google Scholar 

  • Kendler KS, Baker JH. Genetic influences on measures of the environment: a systematic review. Psychol Med. 2007;37:615–26.

    Article  PubMed  Google Scholar 

  • Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry. 1995;52:1048–60.

    Article  PubMed  Google Scholar 

  • Kessler RC, Berglund P, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593–602.

    Article  PubMed  Google Scholar 

  • Kessler RC, McLaughlin KA, Green JG, et al. Childhood adversities and adult psychopathology in the WHO world mental health surveys. Br J Psychiatry. 2010;197:378–85.

    Article  PubMed Central  PubMed  Google Scholar 

  • Khoury MJ, Wacholder S. Invited commentary: from genome-wide association studies to gene–environment-wide interaction studies–challenges and opportunities. Am J Epidemiol. 2009;169:227–30. discussion 234–5.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kilpatrick D, Koenen K, Ruggiero K, et al. The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry. 2007;164:1693–9.

    Article  PubMed  Google Scholar 

  • Klauke B, Deckert J, Reif A, et al. Serotonin transporter gene and childhood trauma – a G× E effect on anxiety sensitivity. Depress Anxiety. 2011;28:1048–57.

    Article  PubMed  Google Scholar 

  • Koenen K, Saxe G, Purcell S, et al. Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry. 2005;10:1058–9.

    Article  PubMed  Google Scholar 

  • Koenen KC, Nugent NR, Amstadter AB. Gene–environment interaction in posttraumatic stress disorder: review, strategy and new directions for future research. Eur Arch Psychiatry Clin Neurosci. 2008;258:82–96.

    Article  PubMed Central  PubMed  Google Scholar 

  • Koenen KC, Amstadter AB, Nugent NR. Gene–environment interaction in posttraumatic stress disorder: an update. J Trauma Stress. 2009a;22:416–26.

    Article  PubMed Central  PubMed  Google Scholar 

  • Koenen KC, Aiello AE, Bakshis E, et al. Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. Am J Epidemiol. 2009b;169:704–11.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kolassa I, Ertl V, Eckart C, et al. Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: evidence from survivors of the Rwandan genocide. J Clin Psychiatry. 2010;71:543–7.

    Article  PubMed  Google Scholar 

  • Krull JL. Using multilevel analyses with sibling data to increase analytic power: an illustration and simulation study. Dev Psychol. 2007;43:602–19.

    Article  PubMed  Google Scholar 

  • La Greca AM, Lai BS, Joormann J, Auslander BB, Short MA. Children’s risk and resilience following a natural disaster: genetic vulnerability, posttraumatic stress, and depression. J Affect Disord. 2013;151:860–7.

    Article  PubMed  Google Scholar 

  • Lupien SJ, King S, Meaney MJ, McEwen BS. Can poverty get under your skin? basal cortisol levels and cognitive function in children from low and high socioeconomic status. Dev Psychopathol. 2001;13:653–76.

    Article  Google Scholar 

  • Lyons MJ, Genderson M, Grant MD, Logue M, Zink T, McKenzie R, Franz CE, Panizzon M, Lohr JB, Jerskey B, Kremen WS. Gene-environment interaction of ApoE genotype and combat exposure on PTSD. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:762–9.

    Article  PubMed  Google Scholar 

  • Maroun M, Kavushansky A, Holmes A, Wellman C, Motanis H. Enhanced extinction of aversive memories by high-frequency stimulation of the rat infralimbic cortex. PLoS One. 2012;7:e35853.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mehta D, Binder EB. Gene × environment vulnerability factors for PTSD: the HPA-axis. Neuropharmacology. 2012;62:654–62.

    Article  PubMed  Google Scholar 

  • Mercer KB, Orcutt HK, Quinn JF, et al. Acute and posttraumatic stress symptoms in a prospective gene × environment study of a university campus shooting. Arch Gen Psychiatry. 2012;69:89–97.

    Article  PubMed Central  PubMed  Google Scholar 

  • Moffitt TE, Caspi A, Rutter M. Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry. 2005;62:473–81.

    Article  PubMed  Google Scholar 

  • Mustapić M, Pivac N, Kozarić-Kovačić D, Deželjin M, Cubells JF, Mück-Šeler D. Dopamine beta-hydroxylase (DBH) activity and-1021C/T polymorphism of DBH gene in combat-related post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144:1087–9.

    Article  Google Scholar 

  • Nelson EC, Agrawal A, Pergadia ML, et al. Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Mol Psychiatry. 2009;14:234–5.

    Article  PubMed Central  PubMed  Google Scholar 

  • Norris FH, Tracy M, Galea S. Looking for resilience: understanding the longitudinal trajectories of responses to stress. Soc Sci Med. 2009;68:2190–8.

    Article  PubMed  Google Scholar 

  • Orsini CA, Maren S. Neural and cellular mechanisms of fear and extinction memory formation. Neurosci Biobehav Rev. 2012;36:1773–802.

    Article  PubMed Central  PubMed  Google Scholar 

  • Pietrzak RH, Galea S, Southwick SM, Gelernter J. Examining the relation between the serotonin transporter 5-HTTPLR genotype x trauma exposure interaction on a contemporary phenotypic model of posttraumatic stress symptomatology: a pilot study. J Affect Disord. 2013;148:123–8.

    Article  PubMed Central  PubMed  Google Scholar 

  • Reid WJ, Crisafulli A. Marital discord and child behavior problems: a meta-analysis. J Abnorm Child Psychol. 1990;18:105–17.

    Article  PubMed  Google Scholar 

  • Repetti R, Taylor SE, Saxbe D. The influence of early socialization experiences on the development of biological systems. In: Handbook of socialization: theory and research. New York: Guilford Publications. 2007. p. 124–52.

    Google Scholar 

  • Risch N, Herrell R, Lehner T, et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA. 2009;301:2462–71.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rutter M. Gene–environment interdependence. Eur J Dev Psychol. 2012;9:391–412.

    Article  Google Scholar 

  • Rutter M, Moffitt TE, Caspi A. Gene–environment interplay and psychopathology: multiple varieties but real effects. J Child Psychol Psychiatr. 2006;47:226–61.

    Article  Google Scholar 

  • Schiller D, Monfils M, Raio CM, Johnson DC, LeDoux JE, Phelps EA. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature. 2009;463:49–53.

    Article  PubMed Central  PubMed  Google Scholar 

  • Schoedl AF, Costa MCP, Mari JJ, et al. The clinical correlates of reported childhood sexual abuse: an association between age at trauma onset and severity of depression and PTSD in adults. J Child Sex Abuse. 2010;19:156–70.

    Article  Google Scholar 

  • Smoller JW, Paulus MP, Fagerness JA, et al. Influence of RGS2 on anxiety-related temperament, personality, and brain function. Arch Gen Psychiatry. 2008;65:298–308.

    Article  PubMed  Google Scholar 

  • Tarullo AR, Gunnar MR. Child maltreatment and the developing HPA axis. Horm Behav. 2006;50:632–9.

    Article  PubMed  Google Scholar 

  • Taylor SE, Way BM, Seeman TE. Early adversity and adult health outcomes. Dev Psychopathol. 2011;23:939–54.

    Article  PubMed  Google Scholar 

  • Thakur GA, Joober R, Brunet A. Development and persistence of posttraumatic stress disorder and the 5-HTTLPR polymorphism. J Trauma Stress. 2009;22:240–3.

    Article  PubMed  Google Scholar 

  • Uddin M, Chang SC, Zhang C, Ressler K, Mercer KB, Galea S, Keyes KM, McLaughlin KA, Wildman DE, Aiello AE, Koenen KC. Adcyap1r1 genotype, posttraumatic stress disorder, and depression among women exposed to childhood maltreatment. Depress Anxiety. 2013;30:251–8.

    Article  PubMed Central  PubMed  Google Scholar 

  • Valentiner DP, Holahan CJ, Moos RH. Social support, appraisals of event controllability, and coping: an integrative model. J Pers Soc Psychol. 1994;66:1094–102.

    Article  Google Scholar 

  • van den Oord EJ. Estimating effects of latent and measured genotypes in multilevel models. Stat Methods Med Res. 2001;10:393–407.

    Article  PubMed  Google Scholar 

  • Wieck A, Grassi-Oliveira R, Hartmann do Prado C, Teixeira AL, Bauer ME. Neuroimmunoendocrine interactions in post-traumatic stress disorder: focus on long-term implications of childhood maltreatment. Neuroimmunomodulation. 2014;21:145–51.

    PubMed  Google Scholar 

  • Williams LM, Gatt JM, Schofield PR, Olivieri G, Peduto A, Gordon E. ‘Negativity bias’ in risk for depression and anxiety: brain–body fear circuitry correlates, 5-HTT-LPR and early life stress. Neuroimage. 2009;47:804–14.

    Article  PubMed  Google Scholar 

  • Wolf E, Mitchell K, Koenen K, Miller M. Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder. Psychol Med. 2013;44:1499–509.

    Article  PubMed Central  PubMed  Google Scholar 

  • Woon FL, Hedges DW. Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus. 2008;18:729–36.

    Article  PubMed  Google Scholar 

  • Xie P, Kranzler HR, Poling J, et al. Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology. 2010;35:1684–92.

    PubMed Central  PubMed  Google Scholar 

  • Xie P, Kranzler HR, Farrer L, Gelernter J. Serotonin transporter 5-HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: a replication study. Am J Med Genet B Neuropsychiatr Genet. 2012;159:644–52.

    Article  Google Scholar 

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Authors and Affiliations

  1. University of Modena and Reggio Emilia, Modena, Italy

    Barbara Forresi & Ernesto Caffo

  2. Department of Psychiatry and Neurosciences, Laval University & Centre de Recherche Institut Universitaire en Santé Mentale de Québec, Room F 4439 2601, QC G1J 2G3, Québec City, QC, Canada

    Marco Battaglia

Authors
  1. Barbara Forresi
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  2. Ernesto Caffo
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  3. Marco Battaglia
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Corresponding author

Correspondence to Marco Battaglia .

Editor information

Editors and Affiliations

  1. Buckinghamshire New University, Uxbridge, Middlesex, United Kingdom

    Colin R. Martin

  2. Kings College, London, United Kingdom

    Victor R. Preedy

  3. University of Westminster, London, United Kingdom

    Vinood B. Patel

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Forresi, B., Caffo, E., Battaglia, M. (2015). Gene Environment Interplays: Why PTSD Makes a Good Case for Gene–Environment Interaction Studies and How Adding a Developmental Approach Can Help. In: Martin, C., Preedy, V., Patel, V. (eds) Comprehensive Guide to Post-Traumatic Stress Disorder. Springer, Cham. https://doi.org/10.1007/978-3-319-08613-2_84-1

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  • DOI: https://doi.org/10.1007/978-3-319-08613-2_84-1

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