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An epistasis between dopaminergic and oxytocinergic systems confers risk of post-traumatic stress disorder in a traumatized Chinese cohort.

ABSTRACT: Post-traumatic stress disorder (PTSD) is a psychiatric syndrome that occurs after trauma exposure. Neurotransmitters such as dopamine and oxytocin have been reported to be involved in neuropathology of PTSD. Previous studies indicated that the dopamine-oxytocin interaction may contribute to behavioral disorders. Thus, exploring the epistasis (gene-gene interaction) between oxytocinergic and dopaminergic systems might be useful to reveal the genetic basis of PTSD. In this study, we analyzed two functional single nucleotide polymorphisms (SNPs), rs2268498 for oxytocinergic gene OXTR and rs1801028 for dopaminergic gene DRD2 based on putative oxytocin receptor-dopamine receptor D2 (OTR-DR2) heterocomplex in a Chinese cohort exposed to the 2008 Wenchuan earthquake (156 PTSD cases and 978 controls). Statistical analyses did not find any single variant or gene-environment interaction (SNP?×?earthquake-related trauma exposure) associated with provisional PTSD diagnosis or symptoms. An OXTR-DRD2 interaction (rs2268498?×?rs1801028) was identified to confer risk of provisional PTSD diagnosis (OR?=?9.18, 95% CI?=?3.07-27.46 and P?=?7.37e-05) and further subset analysis indicated that rs2268498 genotypes controlled the association directions of rs1801028 and rs1801028 genotypes also controlled the association directions of rs2268498. Rs2268498?×?rs1801028 is also associated with PTSD symptoms (P?=?0.043). Our study uncovered a genetic and putative function-based contribution of dopaminergic-oxytocinergic system interaction to PTSD.

SUBMITTER: Zhang K

PROVIDER: S-EPMC6917732 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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An epistasis between dopaminergic and oxytocinergic systems confers risk of post-traumatic stress disorder in a traumatized Chinese cohort.

Zhang Kunlin K Li Gen G Wang Li L Cao Chengqi C Fang Ruojiao R Luo Shu S Liu Ping P Zhang Xiang Yang XY

Scientific reports 20191217 1

Post-traumatic stress disorder (PTSD) is a psychiatric syndrome that occurs after trauma exposure. Neurotransmitters such as dopamine and oxytocin have been reported to be involved in neuropathology of PTSD. Previous studies indicated that the dopamine-oxytocin interaction may contribute to behavioral disorders. Thus, exploring the epistasis (gene-gene interaction) between oxytocinergic and dopaminergic systems might be useful to reveal the genetic basis of PTSD. In this study, we analyzed two f ...[more]

PMID: 31848444

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Project description:Increasing evidence supports a close link between REM sleep and the consolidation of emotionally toned memories such as traumatic experiences. In order to investigate the role of sleep for the development of symptoms related to traumatic experiences, beyond experimental models in the laboratory, sleep of acutely traumatised individuals may be examined on the first night after trauma. This might allow us to identify EEG variables predicting the development of posttraumatic stress disorder (PTSD) symptoms, and guide the way to novel sleep interventions to prevent PTSD. Based on our experience, patients' acceptance of polysomnography in the first hours after treatment in an emergency room poses obstacles to such a strategy. Wearable, self-applicable sleep recorders might be an option for the investigation of sleep in the aftermath of trauma. They would considerably decrease the perceived burden for patients and thus increase the likelihood of successful patient recruitment. As one potential sleep intervention, sleep deprivation directly after trauma has been suggested to reduce the consolidation of traumatic memories and hence act as a secondary preventive measure. However, experimental data from sleep deprivation studies in healthy volunteers with the trauma film paradigm have been inconclusive regarding the beneficial or detrimental effects of sleep on traumatic memory processing. Depending on further insights into the role of sleep in traumatic memory consolidation through observational and experimental studies, several options for therapeutic sleep interventions are conceivable: besides behavioural sleep deprivation, selective REM sleep suppression or enhancement by a pharmacological intervention into the serotonergic, noradrenergic or cholinergic systems might provide novel therapeutic options. While REM-modulating drugs have been used with some success for the prevention of PTSD after trauma, they have never been tried before the first night of sleep. In conclusion, more experimental and observational research is needed before sleep interventions are performed in actual trauma victims.

Project description:Background: In our analysis of adolescents affected by the 2016 Fort McMurray wildfire, we observed many negative mental health effects in individuals with a prior history of psychological trauma. Elevated rates of depression and markers of post-traumatic stress disorder (PTSD) were observed, consistent with the hypothesis that prior trauma may reduce sensitivity thresholds for later psychopathology (stress sensitization). Surprisingly, levels of anxiety did not differ based on prior trauma history, nor were retraumatized individuals at increased risk for recent (past month) suicidal ideation. These results are more suggestive of inoculation by prior trauma than stress sensitization. This led us to consider whether individuals with a prior trauma history showed evidence of Post-Traumatic Growth (PTG), a condition in which the experience of a previous trauma leads to areas of sparing or even improvement. Method: To investigate this issue, we generated a structural equation model (SEM) exploring the role of anxiety in previously traumatized (n = 295) and wildfire trauma alone (n = 740) groups. Specifically, models were estimated to explore the relationship between hopelessness, anxiety, PTSD symptoms, self-efficacy and potential protective factors such as friend and family support in both groups. The model was tested using a cross-sectional sample of affected youth, comparing effects between the two groups. Results: While both models produced relatively good fit, differences in the effects and chi-squared values led us to conclude that the groups are subject to different causal specifications in a number of areas, although details warrant caution pending additional investigation. Discussion: We found that adolescents with a prior trauma history appear to have a more realistic appraisal of potential difficulties associated with traumatic events, and seem less reactive to potentially unsettling PTSD symptoms. They also seemed less prone to overconfidence as they got older, an effect seen in the adolescents without a history of trauma. Our findings provide preliminary evidence that the construct of anxiety may work differently in newly traumatized and retraumatized individuals, particularly in the context of mass trauma events.

Dataset Information

An epistasis between dopaminergic and oxytocinergic systems confers risk of post-traumatic stress disorder in a traumatized Chinese cohort.

Publications

An epistasis between dopaminergic and oxytocinergic systems confers risk of post-traumatic stress disorder in a traumatized Chinese cohort.

Similar Datasets

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