Environmental stress, oxytocin receptor gene (OXTR) polymorphism, and mental health following collective stress

Lucas‐Thompson, Rachel G.; Holman, E. Alison

doi:10.1016/j.yhbeh.2013.02.015

Cited by 46 publications

(31 citation statements)

References 75 publications

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“…Veterans with insecure attachment were at significantly higher risk of meeting screening criteria for PTSD if they had at least one rs53576*A compared to G homozygotes. This finding parallels results showing that insecurely attached individuals with an A allele were more socially anxious than G homozygotes (Notzon et al, 2016), and that OXTR rs53575 genotype interacted with negative social environments to predict PTSD symptoms (Lucas-Thompson and Holman, 2013). Further, the association between insecure attachment style and greater likelihood of probable PTSD is consistent with longitudinal observations of the effect of insecure attachment on PTSD symptoms (Franz et al, 2014) and extends previous findings in military samples (Currier et al, 2012; Escolas et al, 2012) to a nationally representative sample, and is clinically relevant given that an insecure attachment style has been linked to reduced treatment response among veterans with PTSD (Forbes et al, 2010).…”

Section: Discussionsupporting

confidence: 84%

“…Given higher rates of PTSD in women (Olff et al, 2007), preliminary evidence of rs53576 genotype × sex interactions predicting activity in limbic areas (Tost et al, 2010), and sex differences in fear and stress responses (Taylor et al, 2000), future studies could explore the potential role of sex in OXTR rs53576 × environment interactions on stress- and trauma-related phenotypes like PTSD. Lucas-Thompson and Holman (2013) found that men’s functioning in response to economic stress was moderated by both OXTR genotype and negative social environments, whereas among women, functioning was associated with negative social environments regardless of genotype and economic stress. These findings suggest the possibility that environmental variables exert more direct influences on women, and are more likely to interact with genetic vulnerabilities in men.…”

Section: Discussionmentioning

confidence: 91%

“…In the only published study of OXTR rs53576 genotype and PTSD symptoms, among individuals with an A allele, a perceived negative social environment was associated with significantly increased PTSD symptoms (regardless of economic stress), while among G homozygotes, a negative social environment predicted elevated PTSD symptoms only for individuals reporting high economic stress (Lucas-Thompson and Holman, 2013). Thus, the G/G genotype may be protective against poor mental health outcomes in the context of negative social environments (e.g., insecure attachment).…”

mentioning

confidence: 96%

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Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

Sippel

Han

Watkins

et al. 2017

Journal of Psychiatric Research

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The human oxytocin system is implicated in social behavior and stress recovery. Polymorphisms in the oxytocin receptor gene (OXTR) may interact with attachment style to predict stress-related psychopathology like posttraumatic stress disorder (PTSD). The objective of this study was to examine independent and interactive effects of the OXTR single nucleotide polymorphism (SNP) rs53576, which has been associated with stress reactivity, support-seeking, and PTSD in prior studies, and attachment style on risk for PTSD in a nationally representative sample of 2163 European-American (EA) U.S. military veterans who participated in two independent waves of the National Health and Resilience in Veterans Study (NHRVS). Results revealed that insecure attachment style [adjusted odds ratio (OR)=4.29; p<0.001] and the interaction of rs53576 and attachment style (OR=2.58, p=0.02) were associated with probable lifetime PTSD. Among individuals with the minor A allele, the prevalence of probable PTSD was significantly higher among those with an insecure attachment style (23.9%) than those with a secure attachment style (2.0%), equivalent to an adjusted OR of 10.7. We attempted to replicate these findings by utilizing dense marker data from a genome-wide association study of 2,215 high-risk civilians; one OXTR variant, though not rs53576, was associated with PTSD. Exploratory analyses in the veteran sample revealed that the interaction between this variant and attachment style predicting probable PTSD approached statistical significance. Results indicate that polymorphisms in the OXTR gene and attachment style may contribute to vulnerability to PTSD in U.S. military veterans.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 96%

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Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

Sippel

Han

Watkins

et al. 2017

Journal of Psychiatric Research

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“…Oxytocin-related genes have continued being the variants most commonly associated with areas related to social functioning, and with impacts of social environments on the individual, in a variety of samples [59–61]. However the picture is far from clear; the relationships between oxytocin and social behaviour are complex, and epigenetic mechanisms play a crucial role [62, 63].…”

Section: Resultsmentioning

confidence: 99%

“…However the picture is far from clear; the relationships between oxytocin and social behaviour are complex, and epigenetic mechanisms play a crucial role [62, 63]. Moreover, given the known influence of estrogens on oxytocin receptor activity, gender could also impact the intensity and/or direction of this association [59, 61]. Additionally, gene variants that appear to be related to serotonergic pathways (e.g, HTR2A [53]) and dopaminergic pathways (e.g., DRD4 [64] and MAO-A [65]), or to psychiatric vulnerability, have continued to be reported as associated to social functioning domains [53, 64, 66].…”

Section: Resultsmentioning

confidence: 99%

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update

Sprangers

Thong

Bartels³

et al. 2014

Qual Life Res

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Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL.

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Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene

Kushner¹,

Herzhoff

Vrshek‐Schallhorn

et al. 2017

Aggressive Behavior

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Interpersonal stress arising from relational aggression (RA)-the intentional effort to harm others via rejection and exclusion-may increase risk for depression in youth. Biological vulnerabilities related to the hormone oxytocin, which affects social behavior and stress responses, may exacerbate this risk. In a community sample of 307 youth (52% female; age range = 10-14 years), we tested whether (1) the association between RA and subsequent depressive symptoms was mediated through social problems and (2) a single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) moderated this indirect association between RA and depression, where GG homozygotes are predicted to be more sensitive to the effects of social problems than A-allele carriers. Youth-reported RA and depressive symptoms were measured using a structured interview and a questionnaire, respectively. DNA was extracted from saliva collected with Oragene kits. Consistent with the interpersonal theory of depression, the association between relational aggression and subsequent depressive symptoms was mediated by social problems. This indirect effect was further moderated by rs53576 genotype, such that GG homozygotes showed a stronger mediation effect than A-carriers. These results suggest that rs53576 variants confer vulnerability for depression within the context of interpersonal risk factors, such that youth with the GG genotype may be particularly sensitive to the social consequences resulting from RA.

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Environmental stress, oxytocin receptor gene (OXTR) polymorphism, and mental health following collective stress

Cited by 46 publications

References 75 publications

Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

Oxytocin receptor gene polymorphisms, attachment, and PTSD: Results from the National Health and Resilience in Veterans Study

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update

Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene

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