Novel GxE Effects and Resilience: A Case:control Longitudinal Study of Psychosocial Stress with War-affected Youth

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Apr 4

PMID 35377919

Authors

Connie J Mulligan

Christopher J Clukay

Anthony Matarazzo

Kristin Hadfield

Lisa Nevell

Rana Dajani

Catherine Panter-Brick

Affiliations

Soon will be listed here.

Abstract

Responses to early life adversity differ greatly across individuals. Elucidating which factors underlie this variation can help us better understand how to improve health trajectories. Here we used a case:control study of refugee and non-refugee youth, differentially exposed to war-related trauma, to investigate the effects of genetics and psychosocial environment on response to trauma. We investigated genetic variants in two genes (serotonin transporter, 5-HTT, and catechol-O-methyltransferase, COMT) that have been implicated in response to trauma. We collected buccal samples and survey data from 417 Syrian refugee and 306 Jordanian non-refugee youth who were enrolled in a randomized controlled trial to evaluate a mental health-focused intervention. Measures of lifetime trauma exposure, resilience, and six mental health and psychosocial stress outcomes were collected at three time points: baseline, ~13 weeks, and ~48 weeks. We used multilevel models to identify gene x environment (GxE) interactions and direct effects of the genetic variants in association with the six outcome measures over time. We did not identify any interactions with trauma exposure, but we did identify GxE interactions with both genes and resilience; 1) individuals with high expression (HE) variants of 5-HTTLPR and high levels of resilience had the lowest levels of perceived stress and 2) individuals homozygous for the Val variant of COMT with high levels of resilience showed stable levels of post-traumatic stress symptoms. We also identified a direct protective effect of 5-HTTLPR HE homozygotes on perceived insecurity. Our results point to novel interactions between the protective effects of genetic variants and resilience, lending support to ideas of differential susceptibility and altered stress reactivity in a cohort of war-affected adolescents.

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References

Oral R, Ramirez M, Coohey C, Nakada S, Walz A, Kuntz A . Adverse childhood experiences and trauma informed care: the future of health care. Pediatr Res. 2015; 79(1-2):227-33. DOI: 10.1038/pr.2015.197. View

Punamaki R, Palosaari E, Diab M, Peltonen K, Qouta S . Trajectories of posttraumatic stress symptoms (PTSS) after major war among Palestinian children: Trauma, family- and child-related predictors. J Affect Disord. 2014; 172:133-40. DOI: 10.1016/j.jad.2014.09.021. View

Lachman H, Papolos D, Saito T, Yu Y, Szumlanski C, Weinshilboum R . Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996; 6(3):243-50. DOI: 10.1097/00008571-199606000-00007. View

Klauke B, Winter B, Gajewska A, Zwanzger P, Reif A, Herrmann M . Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma. PLoS One. 2012; 7(6):e39709. PMC: 3382176. DOI: 10.1371/journal.pone.0039709. View

Caspi A, Moffitt T, Cannon M, McClay J, Murray R, Harrington H . Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005; 57(10):1117-27. DOI: 10.1016/j.biopsych.2005.01.026. View

Mahfoud Z, Abdulrahim S, Taha M, Harpham T, El Hajj T, Makhoul J . Validation of the Arab Youth Mental Health scale as a screening tool for depression/anxiety in Lebanese children. Child Adolesc Psychiatry Ment Health. 2011; 5:9. PMC: 3070665. DOI: 10.1186/1753-2000-5-9. View

Lovallo W, Cohoon A, Sorocco K, Vincent A, Acheson A, Hodgkinson C . Early-Life Adversity and Blunted Stress Reactivity as Predictors of Alcohol and Drug use in Persons With COMT (rs4680) Val158Met Genotypes. Alcohol Clin Exp Res. 2019; 43(7):1519-1527. PMC: 6602827. DOI: 10.1111/acer.14079. View

Flasbeck V, Moser D, Pakusch J, Kumsta R, Brune M . The association between childhood maltreatment and empathic perspective taking is moderated by the 5-HTT linked polymorphic region: Another example of "differential susceptibility". PLoS One. 2019; 14(12):e0226737. PMC: 6922468. DOI: 10.1371/journal.pone.0226737. View

Hu X, Lipsky R, Zhu G, Akhtar L, Taubman J, Greenberg B . Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 2006; 78(5):815-826. PMC: 1474042. DOI: 10.1086/503850. View

10.

van Roekel E, Verhagen M, Engels R, Kuppens P . Variation in the serotonin transporter polymorphism (5-HTTLPR) and inertia of negative and positive emotions in daily life. Emotion. 2017; 18(2):229-236. DOI: 10.1037/emo0000336. View

11.

Munafo M, Bowes L, Clark T, Flint J . Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry. 2005; 10(8):765-70. DOI: 10.1038/sj.mp.4001664. View

12.

Boussetta S, Cherni L, Pakstis A, Ben Salem N, Elkamel S, Khodjet-El-Khil H . Usefulness of COMT gene polymorphisms in North African populations. Gene. 2019; 696:186-196. DOI: 10.1016/j.gene.2019.02.021. View

13.

Assary E, Vincent J, Keers R, Pluess M . Gene-environment interaction and psychiatric disorders: Review and future directions. Semin Cell Dev Biol. 2017; 77:133-143. DOI: 10.1016/j.semcdb.2017.10.016. View

14.

Reed R, Fazel M, Jones L, Panter-Brick C, Stein A . Mental health of displaced and refugee children resettled in low-income and middle-income countries: risk and protective factors. Lancet. 2011; 379(9812):250-65. DOI: 10.1016/S0140-6736(11)60050-0. View

15.

Ramsay H, Kelleher I, Flannery P, Clarke M, Lynch F, Harley M . Relationship between the COMT-Val158Met and BDNF-Val66Met polymorphisms, childhood trauma and psychotic experiences in an adolescent general population sample. PLoS One. 2013; 8(11):e79741. PMC: 3818212. DOI: 10.1371/journal.pone.0079741. View

16.

Curran P, Obeidat K, Losardo D . Twelve Frequently Asked Questions About Growth Curve Modeling. J Cogn Dev. 2011; 11(2):121-136. PMC: 3131138. DOI: 10.1080/15248371003699969. View

17.

Panter-Brick C, Eggerman M, Ager A, Hadfield K, Dajani R . Measuring the psychosocial, biological, and cognitive signatures of profound stress in humanitarian settings: impacts, challenges, and strategies in the field. Confl Health. 2020; 14:40. PMC: 7310257. DOI: 10.1186/s13031-020-00286-w. View

18.

Clukay C, Dajani R, Hadfield K, Quinlan J, Panter-Brick C, Mulligan C . Association of MAOA genetic variants and resilience with psychosocial stress: A longitudinal study of Syrian refugees. PLoS One. 2019; 14(7):e0219385. PMC: 6636744. DOI: 10.1371/journal.pone.0219385. View

19.

van Winkel R, Henquet C, Rosa A, Papiol S, Fananas L, De Hert M . Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. Am J Med Genet B Neuropsychiatr Genet. 2007; 147B(1):10-7. DOI: 10.1002/ajmg.b.30559. View

20.

Uwizeye G, Thayer Z, DeVon H, McCreary L, McDade T, Mukamana D . Double Jeopardy: Young adult mental and physical health outcomes following conception via genocidal rape during the 1994 genocide against the Tutsi in Rwanda. Soc Sci Med. 2021; 278:113938. DOI: 10.1016/j.socscimed.2021.113938. View