Effects of Different Stressors Are Modulated by Different Neurobiological Systems: The Role of GABA-A Versus CB1 Receptor Gene Variants in Anxiety and Depression
Effects of Different Stressors Are Modulated by Different Neurobiological Systems: The Role of GABA-A Versus CB1 Receptor Gene Variants in Anxiety and Depression
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DOI：
10.3389/fncel.2019.00138
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发表时间：
2019-04-09
影响因子：
5.3
通讯作者：
Bagdy, Gyorgy
中科院分区：
文献类型：
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作者：
Gonda, Xenia;Petschner, Peter;Bagdy, Gyorgy
环境压力及其与遗传变异的交互作用是抑郁症和焦虑症发生的关键因素，但在这些精神症状的背景下，未能识别出可复制的遗传变异和基因交互作用。最近有报道称，在抑郁症的发展过程中，5-HTTLPR和NOSI与经济因素相互作用，但不与其他类型的近期应激源相互作用。在这项研究中，我们调查了GABRA6 rs3219151和CNR1 rs7766029与不同类型的近期生活事件在大样本人群中抑郁和焦虑的相互作用。2191名参与者完成了威胁经历清单问卷，该问卷涵盖了前一年经历的四类应激性生活事件(经济问题、疾病/个人问题、亲密关系和社交网络)以及抑郁和焦虑症状的简短症状清单。参与者接受了rs3219151和rs7766029的基因分型。以年龄、性别为协变量，采用线性回归模型进行分析。结果表明，在抑郁和焦虑症状中，CNR1rs7766029与经济生活事件有显著的交互作用，而与其他类型的生活事件无交互作用。相比之下，GABRA6rs3219151在焦虑时与社交网络相关的生活事件和在抑郁时与疾病/个人问题相关的生活事件显示出显著的交互作用。我们的结果表明，不同类型的近期压力对心理的影响可能通过不同的分子遗传途径进行不同的调节。此外，在某些基因变异的情况下，出现的精神症状可能取决于所经历的压力类型。
Environmental stress and its interaction with genetic variation are key contributors in the development of depression and anxiety, yet there is a failure to identify replicable genetic variants and gene-interaction effects in the background of these psychiatric symptoms. Recently it has been reported that 5-HTTLPR and NOSI interact with financial but not other types of recent stressors in the development of depression. In the present study we investigated the interaction of GABRA6 rs3219151 and CNR1 rs7766029 in interaction with different types of recent life events on the presence of depression and anxiety in a large general population sample. 2191 participants completed the List of Threatening Experiences questionnaire which covers four categories of stressful life events (financial problems, illness/personal problems, intimate relationships, and social network) experienced over the previous year and the Brief Symptom Inventory for depression and anxiety symptoms. Participants were genotyped for rs3219151 and rs7766029. Data were analyzed with linear regression models with age and gender as covariates. Results indicated that CNR1 rs7766029 interacted significantly with financial but not other types of life events both in case of depression and anxiety symptoms. In contrast, GABRA6 rs3219151 showed a significant interaction with social network related life events in case of anxiety and with illness/personal problem-related life events in case of depression. Our results suggest that the psychological impact of different types of recent stress may be differentially modulated by distinct molecular genetic pathways. Furthermore, in case of certain genetic variants, the occurring psychiatric symptom may depend on the type of stress experienced.