15Background: In major depressive disorder (MDD), it is unclear to what extent structural brain changes are associated with depressive episodes or represent part of the mechanism by which the risk for illness is mediated. The aim of this study was to investigate whether structural abnormalities are related to risk for the development of MDD. Methods: We compared healthy controls with a positive family history for MDD (HC-FHP), healthy controls with no family history of any psychiatric disease (HC-FHN) and patients with MDD. Groups were age-and sex-matched. We analyzed data from high-resolution magnetic resonance imaging using voxel-based morphometry. We performed small volume corrections for our regions of interest (hippocampus, dorsolateral [DLPFC] and dorsomedial prefrontal cortex [DMPFC], anterior cingulate cortex [ACC] and basal ganglia) using a family-wise error correction (p < 0.05) to control for multiple comparisons. Results: There were 30 participants in the HC-FHP group, 64 in the HC-FHN group and 33 patients with MDD. The HC-FHP group had smaller right hippocampal and DLPFC grey matter volumes compared with the HC-FHN group, and even smaller right hippocampal volumes compared with patients with MDD. In addition, the HC-FHP group exhibited smaller white matter volumes in the DLPFC and left putamen but also greater volumes in 2 areas of the DMPFC compared with the HC-FHN group. Patients with MDD exhibited smaller volumes in the ACC, DMPFC, DLPFC and the basal ganglia compared with healthy controls. Limitations: The retrospective identification of family history might result in a bias toward unidentified participants in the control group at risk for MDD, diminishing the effect size. Conclusion: Volume reductions in the hippocampus and DLPFC might be associated with a greater risk for MDD. The HC-FHP group had smaller hippocampal volumes compared with patients with MDD, which is suggestive for neuroplastic effects of treatment. The HC-FHP group had not yet experienced a depressive episode and therefore might have been resilient and might have had some protective strategies. Whether resilience is associated with the larger white matter volumes in the DMPFC (e.g., owing to compensatory, neuroplastic remodelling mechanisms) needs to be confirmed in future studies.

The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.

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The aim of this study was to evaluate the efficacy and tolerability of quetiapine combined with lithium or divalproex in the treatment of bipolar mania. Patients were randomized to 6 weeks of quetiapine (up to 800 mg/day) and lithium/divalproex (Li/DVP) (target trough serum concentrations of 0.7-1.0 mEq/L and 50-100 microg/mL, respectively) or placebo and lithium/divalproex. Quetiapine+lithium/divalproex treatment (n=104) showed a 2.0-point greater improvement on the primary outcome (change from baseline in Young Mania Rating Scale total score at day 21) compared with placebo+lithium/divalproex (n=96), and a 2.8-point greater difference by day 42, but the differences between groups were not statistically significant. Other efficacy measures, however, did show a statistically significant advantage in favor of quetiapine+lithium/divalproex over lithium/divalproex monotherapy at day 42. Improvement of mean Young Mania Rating Scale scores with quetiapine+lithium/divalproex was numerically but not statistically significantly greater than lithium/divalproex monotherapy in the treatment of bipolar mania. Potential reasons for the failure of quetiapine+lithium/divalproex to differentiate from placebo+lithium/divalproex treatment on the primary outcome measure and the implications of this for the treatment of mania and future studies are discussed. Overall, the combination of quetiapine with lithium or divalproex was well tolerated.