Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression.
Current understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs1106634 of the ATPV1B2 gene encoding the vacuolar H+ATPase on lifetime and current depression and the possible mediating role of neuroticism by logistic and linear regression in a white European general sample of 2226 subjects. Association of rs1106634 with performance on frontal (Stockings of Cambridge (SOC)) and hippocampal-dependent (paired associates learning (PAL)) cognitive tasks was investigated in multivariate general linear models in a smaller subsample. The ATP6V1B2 rs1106634 A allele had a significant effect on lifetime but not on current depression. The effect of the A allele on lifetime depression was not mediated by neuroticism. The A allele influenced performance on the PAL but not on the SOC test. We conclude that the effects of variation in the vacuolar ATPase may point to a new molecular mechanism that influences the long-term development of depression. This mechanism may involve dysfunction specifically in hippocampal circuitry and cognitive impairment that characterizes recurrent and chronic depression.
Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary.|MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.|Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
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Gonda
MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.|Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
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Eszlari
Neuroscience and Psychiatry Unit, Institute of Brain Behaviour and Mental Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK.|Manchester Academic Health Sciences Centre, Manchester, UK.
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Anderson
Neuroscience and Psychiatry Unit, Institute of Brain Behaviour and Mental Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK.|Manchester Academic Health Sciences Centre, Manchester, UK.|Manchester Mental Health and Social Care Partnership, Chorlton House, Manchester, UK.
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Deakin
MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.|Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
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Bagdy
MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.|Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.|Neuroscience and Psychiatry Unit, Institute of Brain Behaviour and Mental Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK.|Manchester Academic Health Sciences Centre, Manchester, UK.|MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
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Juhasz
D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D005823:Genetics; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000503:physiopathology; D019965:Neurocognitive Disorders / Q000235:genetics* / Q000503:physiopathology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D000075384:Neuroticism / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011594:Psychometrics; D018570:Risk Assessment; D025262:Vacuolar Proton-Translocating ATPases
D025262:Vacuolar Proton-Translocating ATPases; C000599123:ATP6V1B2 protein, human