The monitoring of plasma olanzapine concentrations has been found to be an important and useful tool for optimizing psychiatric treatment. The present study investigated the effect that clinical factors, such as smoking and age, and functional polymorphisms of UGT1A4, CYP1A2, and CYP2D6 genes have on plasma olanzapine concentration, as well as the effects of plasma olanzapine concentrations on Japanese schizophrenic patients' clinical symptoms. The subjects included 51 chronic schizophrenic patients whose symptoms were not controlled with chronic conventional antipsychotics and therefore were switched to olanzapine. Male smokers had a significantly lower olanzapine concentration-dose ratio and olanzapine/4'-N-desmethyl olanzapine ratio (which reflects CYP1A2 activity) than male nonsmokers and female nonsmokers. The results of a 2-way analysis of covariance showed that smoking had the main effect, rather than gender or age. The functional gene polymorphisms that were studied had no effect on the plasma olanzapine and metabolite concentrations. An improved total Brief Psychiatric Rating Scale (BPRS) score was not correlated with the plasma olanzapine concentration, but individual BPRS scores related to improvement of suspiciousness, hallucinations, and blunted affect were significantly correlated with plasma olanzapine concentration. Clinical factors, especially smoking, were more important modulators of olanzapine metabolism than the functional genotypes. Long-term olanzapine treatment with adequate plasma olanzapine concentrations could be more effective in improving some symptoms than treatment with conventional antipsychotics.

Electroconvulsive therapy (ECT) is known as a successful treatment for severe depression. Despite great efforts, the biological mechanisms underlying the beneficial effects of ECT remain largely unclear. In this study, animals received a single, 10, or 20 applications of electroconvulsive seizure (ECS), and then cell proliferation and apoptosis were investigated in the subgranular zone (SGZ) of the dentate gyrus. We analyzed whether a series of ECSs could induce changes in the dentate gyrus in a dose-response fashion. A single-ECS seizure significantly increased cell proliferation in the SGZ by ∼2.3-fold compared to sham treatment. After 10 ECSs, a significant increase in cell proliferation was observed in the SGZ by ∼2.4-fold compared to sham treatment. Moreover, 10 ECSs induced a significant increase in cell proliferation by 1.3-fold compared to a single-ECS group. However, cell proliferation did not differ between the group with 20 ECSs and sham group. In addition, a significant increase in the number of apoptotic cells was found in the group with 10 ECSs, whereas no significant change in it was found in either a single ECS or 20 ECSs group compared to sham treatment. These findings indicate that the optimal number of treatments and duration of stimulation requires investigation. Further studies are needed to elucidate the intracellular mechanisms underlying both effective and excessive ECT.

Background: Probiotics have been reported to ameliorate cognitive impairment. Objective: We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI). Methods: In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer’s disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition. Results: Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale “orientation” was significantly improved compared to placebo at 24 weeks. MMSE subscales “orientation in time” and “writing” were significantly improved compared to placebo in the lower baseline MMSE (<  25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation. Conclusion: Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.

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