Nóra Eszlári1,2, Xénia Gonda1,2,3, Jane Sarginson4,5, Péter Petschner1,2,6, Zoltán Tóth1,7, Dániel Baksa1,8, Gábor Hullám1,9, Ian Muir Anderson10, John Francis William Deakin10, Gabriella Juhász1,2,6,8,10, György Bagdy1,2,6
1 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
2 NAP-2-SE New Antidepressant Target Research Group, Semmelweis University, Budapest, Hungary
3 Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Centre, Semmelweis University, Budapest, Hungary
4 School of Health Sciences, University of Manchester, Manchester, United Kingdom
5 School of Healthcare Science, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, M15GD, United Kingdom
6 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
7 Institute of Communication Engineering, Kando Kalman Faculty of Electrical Engineering, Obuda University, Budapest, Hungary
8 SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Semmelweis University, Budapest, Hungary
9 Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary
10 Neuroscience and Psychiatry Unit, Division of Neuroscience and Experimental Psychology, University of Manchester and Manchester Academic Health Sciences Centre, Manchester, United Kingdom
Suicide characterizes various psychiatric disorders and leads to around 800,000 deaths worldwide. It stems from the interplay between genetic and stress factors.
In our study, we investigated the association of rs3219151 of GABRA6 gene encoding the α6 subunit of the GABAA receptor, both in itself and in interaction with recent life stress, with phenotypes related to suicidal behavior.
975 adults from Budapest and 1308 adults from Manchester were recruited to be genotyped. They provided questionnaire data on lifetime depression, suicide attempt or deliberate self-harm, current depression and anxiety scores (Brief Symptom Inventory, BSI), and number of negative life events in the previous one year (List of Threatening Experiences). Regression equations were run, gender, age and population were covariates, and the false discovery rate method was applied to correct for multiple testing.
GABRA6 rs3219151 in itself was associated with none of the phenotypes, however, in interaction with recent stress, it was associated with all four phenotypes. Nonetheless, this gene-by-environment interaction effect survived correction for multiple testing only on BSI depression and BSI anxiety. These two effects could also be replicated in the separate Budapest and Manchester subsamples. Further analyses on the separate items of BSI depression and anxiety revealed that this gene-by-environment interaction was replicable within the two subsamples only on two items: “Thoughts of ending your life” and “Spells of terror or panic”. In all cases, CC genotype was protective against the harmful effects of serious stress load.
Although GABRA6 rs3219151 does not affect suicidal behavior in itself, it mediates the detrimental effect of recent stressful events on the constellation of symptoms denoting a risk for suicide.
Supported by ÚNKP-17-3-III-SE-2 New National Excellence Program of The Ministry of Human Capacities; Hungarian Academy of Sciences; Hungarian Brain Research Program (KTIA_NAP_13-1-2013-0001, KTIA_13_NAP-A-II/14, KTIA_NAP_13-2-2015-0001, 2017-1.2.1-NKP-2017-00002).
Doctoral School: Doctoral School of Mental Health Sciences
Supervisor: Gabriella Juhász