Although stressful life events (SLEs) have been associated with an increased risk of illness and mental disorder, their impact on brain anatomy remains poorly understood. Using a longitudinal design, we tested the hypothesis that SLEs are significantly associated with changes in gray matter volume (GMV) in brain regions previously implicated in post-traumatic stress disorder (PTSD) in a group of clinically healthy adults. Magnetic resonance imaging was used to acquire an anatomical scan from 26 subjects (13 males and 13 females; mean age ± SD: 25.2 ± 4.3 years), with no psychiatric diagnosis, at two time points with a 3-month interval. Voxel-based morphometry was used to examine an association between SLEs and gray matter changes during this period. The number of SLEs was associated with a decrease in GMV in the anterior cingulate, hippocampus, and parahippocampal gyrus (p < 0.001). In contrast, there were no areas where the number of SLEs was associated with an increase in GMV. These results provide evidence that, in adults with no formal psychiatric diagnosis, SLEs are associated with GMV decreases in a subset of regions implicated in PTSD, and that these alterations can be observed within a period as short as 3 months.

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Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.

Introduction: Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders. Objective: The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers. Aim: We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients. Methods: We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psychophysiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity. Results: In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls. Conclusions: Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.

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