Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders

Binder, Elisabeth B.

doi:10.1080/20008198.2017.1412745

Cited by 24 publications

(14 citation statements)

References 37 publications

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“…childhood trauma) to increase the risk for PTSD. Binder (Binder, 2017) provided an eloquent review of how a key gene within the stress response system, FBKP5, can increase the risk for PTSD. Specifically, with the combination of inherited genetic risk and childhood trauma a reduction in DNA methylation occurs at FKBP5 which disrupts the homoeostasis and may results in lasting alterations of the neural circuits related to stress regulation.…”

Section: Ten Years Of Progress In Genomicsmentioning

confidence: 99%

A decennial review of psychotraumatology: what did we learn and where are we going?

Olff

Amstadter

Armour

et al. 2019

European Journal of Psychotraumatology

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On 6 December 2019 we start the 10th year of the European Journal of Psychotraumatogy (EJPT), a full Open Access journal on psychotrauma. This editorial is part of a special issue/ collection celebrating the 10 years anniversary of the journal where we will acknowledge some of our most impactful articles of the past decade (also discussed below and marked with * in the reference list). In this editorial the editors present a decennial review of the field addressing a range of topics that are core to both the journal and to psychotraumatology as a discipline. These include neurobiological developments (genomics, neuroimaging and neuroendocrine research), forms of trauma exposure and impact across the lifespan, mass trauma and early interventions, work-related trauma, trauma in refugee populations, and the potential consequences of trauma such as PTSD or Complex PTSD, but also resilience. We address innovations in psychological, medication (enhanced) and technologyassisted treatments, mediators and moderators like social support and finally how new research methods help us to gain insights in symptom structures or to better predict symptom development or treatment success. We aimed to answer three questions 1. Where did we stand in 2010? 2. What did we learn in the past 10 years? 3. What are our knowledge gaps? We conclude with a number of recommendations concerning top priorities for the future direction of the field of psychotraumatology and correspondingly the journal.

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Section: Ten Years Of Progress In Genomicsmentioning

confidence: 99%

A decennial review of psychotraumatology: what did we learn and where are we going?

Olff

Amstadter

Armour

et al. 2019

European Journal of Psychotraumatology

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“…Several recent reviews have pointed to a multitude of neurobiological factors believed to play a role in resilience (Feder et al, ; Menard, Pfau, Hodes, & Russo, ; Pfau & Russo, ) including diverse stress response systems (McEwen et al, ). While the potential genetic underpinnings of these factors have begun to receive attention, studies to date have focused on candidate gene (or epigenetic) (Binder, ) involvement (Feder et al, ; McEwen, ; Menard et al, ). Here, we report results from what we believe to be the first GWAS of psychological resilience, and have done so in military population‐based samples.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide analyses of psychological resilience in U.S. Army soldiers

Stein

Choi

Jain

et al. 2019

American J of Med Genetics Pt B

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Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome-wide association studies (GWASs) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self-assessed resilience (N = 11,492) was found to have significant common-variant heritability (h 2 = 0.162, se = 0.050, p = 5.37 × 10 −4 ), and to be significantly negatively genetically correlated with neuroticism (r g = −0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome-wide significant locus on an intergenic region on Chr 4 upstream from doublecortin-like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [p = 5.65 × 10 −9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch-like family member 36 (KLHL36) was detected at gene-wise genomewide significance [p = 1.89 × 10 −6 ]. A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very

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“…Several recent reviews have pointed to a multitude of neurobiological factors believed to play a role in resilience [Feder et al 2018;Menard et al 2016;Pfau and Russo 2015] including diverse stress response systems [McEwen et al 2015]. While the potential genetic underpinnings of these factors have begun to receive attention, studies to date have focused on candidate gene (or epigenetic) [Binder 2017] involvement [Feder et al 2018;McEwen 2016;Menard et al 2016]. Here, we report results from what we believe to be the first GWAS of psychological resilience, and have done so in military population-based samples.…”

Section: Discussionmentioning

confidence: 99%

Genomewide Analyses of Psychological Resilience in US Army Soldiers

Stein

Choi

Jain

et al. 2019

Preprint

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Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genomewide association studies (GWAS) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from pre-to post-deployment) resilience among European (EUR) ancestry soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). Self-assessed resilience (N=11,492) was found to have significant common-variant heritability (h 2 =0.162, se=0.050, p=5.37e-4), and to be significantly negatively genetically correlated with neuroticism (r g = -0.388, p=0.0092). GWAS results from the EUR soldiers revealed a genomewide significant locus (4 SNPs in LD; top SNP: rs4260523, p=5.654e-09) on an intergenic region on Chr 4 upstream from DCLK2(Doublecortin-Like Kinase 2), a member of the doublecortin (DCX) family of kinases that promote survival and regeneration of injured neurons. A second gene, KLHL36 (Kelch Like Family Member 36) was detected at gene-wise genomewide significance (p=1.89e-06). A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genomewide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015) on Chr 12 downstream from SLC15A5 (solute carrier family 15 member 5) in the small group (N=581) of subjects exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and potentially point to new avenues for therapeutic intervention.

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Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders

Cited by 24 publications

References 37 publications

A decennial review of psychotraumatology: what did we learn and where are we going?

A decennial review of psychotraumatology: what did we learn and where are we going?

Genome‐wide analyses of psychological resilience in U.S. Army soldiers

Genomewide Analyses of Psychological Resilience in US Army Soldiers

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