Journal
NEUROPSYCHOPHARMACOLOGY
Volume 40, Issue 11, Pages 2510-2516Publisher
SPRINGERNATURE
DOI: 10.1038/npp.2015.86
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Funding
- German Research Foundation (DFG) [FOR 2107, DA1151/5-1, KO4291/3-1, KI588/14-1, JA1890/7-1]
- DFG [KR3822/2-1, NO246/10-1]
- Innovative Medizinische Forschung (IMF) of the Medical Faculty of Munster [DA120903, DA111107, DA211012]
- Rolf-Dierichs-Stiftung [ZUW80037]
- Interdisziplinares Zentrum fur Klinische Forschung (IZKF) of the Medical Faculty of Munster (research group 4)
- European Community [279227]
- German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under e:Med Programme [01ZX1314A, 01ZX1314G]
- Alfried Krupp von Bohlen und Halbach-Stiftung
- esparma GmbH/Aristo Pharma GmbH
- Lilly Deutschland GmbH
- Servier Deutschland GmbH
- MagVenture GmbH
- Pfizer
- Bristol-Myers Squibb
- Lilly
- Astra Zeneca
- MR: comp GmbH, Testing Services for MR Safety
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Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI data in two independent German samples (healthy subjects, n = 512; depressed inpatients, n = 171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. In addition, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/ fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and regulation. The present data suggest that NCAN forms susceptibility to neurostructural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors.
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