Dataset Information

A DRD2/ANNK1-COMT Interaction, Consisting of Functional Variants, Confers Risk of Post-traumatic Stress Disorder in Traumatized Chinese.

ABSTRACT: Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene-gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of dopamine-related PTSD symptomatology and contribute to precision medicine. Methods: We genotyped seven single nucleotide polymorphisms (SNPs) of three dopaminergic genes DRD2/ANNK1 (rs1800497 and rs1801028), COMT (rs6269, rs4633, rs4818 and rs4680) and DBH (rs1611115), in a Chinese predominantly adult cohort that had been exposed to an earthquake (156 PTSD cases and 978 controls). Results: Statistical genetics analysis identified a DRD2/ANNK1-COMT interaction (rs1800497 × rs6269), which is associated with PTSD diagnosis (Pinteraction = 0.0008055 and Pcorrected = 0.0169155). Single-variant and haplotype-based subset analyses showed that rs1800497 modulates the association directions of both the rs6269 G allele and the rs6269-rs4633-rs4818-rs4680 haplotype G-C-G-G. The interaction (rs1800497 × rs6269) was replicated in a Chinese young female cohort (32 cases and 581 controls, Pinteraction = 0.01329). Conclusions: Rs1800497 is related to the DA receptor D2 density and rs6269-rs4633-rs4818-rs4680 haplotypes affect the catechol O-methyltransferase level and enzyme activity. Thus, the interaction was inferred to be at protein-protein and DA activity level. The genotype combinations of the two SNPs indicate a potential origin of DA homeostasis abnormalities in PTSD development.

SUBMITTER: Zhang K

PROVIDER: S-EPMC5936991 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A DRD2/ANNK1-COMT Interaction, Consisting of Functional Variants, Confers Risk of Post-traumatic Stress Disorder in Traumatized Chinese.

Zhang Kunlin K Wang Li L Cao Chengqi C Li Gen G Fang Ruojiao R Liu Ping P Luo Shu S Zhang Xiangyang X Liberzon Israel I

Frontiers in psychiatry 20180430

Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene-gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of d ...[more]

PMID: 29760667

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Project description:Several lines of evidence suggest that genes involved in dopamine (DA) transmission may contribute to creativity. Among these genes, the catechol-O-methyltransferase gene (COMT) and the dopamine D2 receptor gene (DRD2) are the most promising candidates. Our previous study has revealed evidence for the involvement of DRD2 in creative potential. The present study extended our previous study by systematically exploring the association of COMT with creative potential as well as the interaction between COMT and DRD2. Twelve single nucleotide polymorphisms (SNPs) covering COMT were genotyped in 543 healthy Chinese college students whose creative potentials were assessed by divergent thinking tests. Single SNP analysis showed that rs174697 was nominally associated with verbal originality, two SNPs (rs737865 and rs5993883) were nominally associated with figural fluency, and two SNPs (rs737865 and rs4680) were nominally associated with figural originality. Haplotype analysis showed that, the TCT and CCT haplotype (rs737865-rs174675-rs5993882) were nominally associated with figural originality, and the TATGCAG and CGCGGGA haplotype (rs4646312-rs6269-rs4633-rs6267-rs4818-rs4680-rs769224) were nominally associated with figural originality and verbal flexibility, respectively. However, none of these nominal findings survived correction for multiple testing. Gene-gene interaction analysis identified one significant four-way interaction of rs174675 (COMT), rs174697 (COMT), rs1076560 (DRD2), and rs4436578 (DRD2) on verbal fluency, one significant four-way interaction of rs174675 (COMT), rs4818 (COMT), rs1076560 (DRD2), and rs4648317 (DRD2) on verbal flexibility, and one significant three-way interaction of rs5993883 (COMT), rs4648319 (DRD2), and rs4648317 (DRD2) on figural flexibility. In conclusion, the present study provides nominal evidence for the involvement of COMT in creative potential and suggests that DA related genes may act in coordination to contribute to creativity.

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

A DRD2/ANNK1-COMT Interaction, Consisting of Functional Variants, Confers Risk of Post-traumatic Stress Disorder in Traumatized Chinese.

Publications

A <i>DRD2/ANNK1</i>-<i>COMT</i> Interaction, Consisting of Functional Variants, Confers Risk of Post-traumatic Stress Disorder in Traumatized Chinese.

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