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Front Cell Neurosci. 2019 Apr 9;13:138. doi: 10.3389/fncel.2019.00138. eCollection 2019.

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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Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
Neuroscience and Psychiatry Unit, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biological, Medical and Human Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, United Kingdom.
Greater Manchester Mental Health NHS Foundation Trust, The University of Manchester, Manchester, United Kingdom.
SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Semmelweis University, Budapest, Hungary.


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.


CNR1; GABA; GABRA6; anxiety; depression; endocannabinoid system; gene-environment interaction; types of stress

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