Yokukansan (TJ-54) for treatment of very-late-onset schizophrenia-like psychosis: an open-label study.

BACKGROUND: Although schizophrenia affects all age groups, late or very-late-onset schizophrenia-like psychosis has not been well studied, and various treatment issues remain unresolved. The objective of the present study was to evaluate the efficacy and safety of yokukansan (TJ-54), Japanese herbal medicine, monotherapy in a diagnostically homogenous group of elderly patients without cognitive impairment suffering from very-late-onset schizophrenia. METHODS: Forty patients of mean age 73.1±4.8 years, fulfilling both the recent consensus criteria for very late-onset schizophrenia-like psychosis and the DSM-IV-TR criteria for schizophrenia, were assessed by the brief psychiatric rating scale, the clinical global impression scale-severity, and positive and negative syndrome scale at baseline and after 4 weeks administration of TJ-54 (2.5-7.5 g/day). In addition, abnormal movements were evaluated with the Simpson-Angus scale, Barnes Akathisia scale, and abnormal involuntary movement scale. RESULTS: A highly significant (p<0.001) improvement on all measures of psychotic symptomatology was observed in all patients. TJ-54 was very well tolerated by the patients, and no clinically significant adverse effects were observed. Scores on all abnormal movement scales did not differ significantly prior to and after TJ-54 treatment. CONCLUSION: Preliminary results indicate that TJ-54 appears to be an efficacious and safe herbal medicine for treatment of very-late-onset schizophrenia-like psychosis.

Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model.

BACKGROUND: Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats. METHODS: Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions. We characterized the microglial cells in the hippocampal dentate gyrus. RESULTS: We found that microglial cells showed activated morphology in the hilus, subgranular zone, and granular layer of the Gunn rat hippocampal dentate gyrus. There was no significant difference between cell numbers between in Gunn rats and controls. However, there was significant difference in the area of CD11b expression in the hippocampal dentate gyrus. Ultrastructurally, microglial cells often contained rich enlarged rich organelles in the cytoplasm and showed some phagocytic function. CONCLUSIONS: We propose that activation of microglia could be an important causal factor of the behavioral abnormalities and neuropathological changes in Gunn rats. These findings may provide basic information for further assessment of the Gunn rat as an animal model of schizophrenia.

Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study.

BACKGROUND: Approximately 25% of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression. Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat. It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities, which include neurogenesis, antioxidation, and anti-glutamate excitotoxicity, and may direct regulation of pro-inflammatory agents. METHODS: This was a 6-week, open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult inpatients (n=25) diagnosed with major depression with psychotic features (psychotic depression) according to DSM-IV-TR. The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale (HAM-D-21) score from baseline to week 6. Secondary endpoints were changes in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores from baseline to week 6. Spontaneously reported adverse events were recorded. RESULTS: The patients' average age was 46.9±10.2 years. Minocyline (150 mg/day) in combination with antidepressants (fulvoxamine, paroxetine, and sertraline) provided significant improvement in depression. Mean (± SD) HAM-D-21 was reduced to 6.7±1.9 at week 6 from a baseline value of 40.4±2.5. Significant improvement of psychotic symptoms (mean±SD) was indicated by the decrease in BPRS scores from baseline (63.3±8.7) to week 6 (4.6±2.4). No serious adverse events occurred. CONCLUSIONS: These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression. Further studies using larger, double-blind, parallel-group design are warranted to confirm these findings.