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Impact of family history and depression on amygdala volume.Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study's purpose was to investigate family history's effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala without a family history of MDD. These effects had larger right amygdala than healthy controls without MDD family history. These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants, providing a rationale for the inconsistent results in MDD amygdala studies. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.
The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the 'G' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk 'A' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in 'G' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.