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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.

Several researches indicate that autonomic nervous system (ANS) dysfunction in patients with schizophrenia. Recently, salivary alpha-amylase (sAA) has been employed as a useful marker for ANS function. We investigated the extent of ANS dysfunction by measuring sAA and heart rate variability (HRV) of 25 patients with schizophrenia compared with controls. Schizophrenia group demonstrated a significant increase in sAA and markedly lower parasympathetic nervous system (PNS) activity in the HRV. However, there were no significant differences between two groups in sympathetic nervous system (SNS) activity. We concluded that PNS might be suppressed and the SNS shows relatively high activity in schizophrenia.

BackgroundNumerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger’s disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger’s disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54) may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger’s disorder.MethodsThis was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger’s disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S) and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I).ResultsForty subjects, ages 8–40 years (mean 22.7 ± 7.3 years) received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day). Full-scale intelligence quotient (IQ) scores ranged from 70 to 110 (mean 88.9 ± 13.2). Thirty-six (90%) of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill) and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 (< 0.0001). ABC-I scores ranged from 11 to 29 (mean 17.4 ± 3.66) at baseline, whereas scores at week 12 ranged from 0 to 5 (mean 0.93 ± 0.97) (p <0.0001). TJ-54 was well tolerated. No subject exited the study due to a drug-related adverse event.ConclusionsThese preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger’s disorder. However, given the characteristics of this trial, the present findings should be taken cautiously, and larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of TJ-54 in this understudied population.

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Aims:Previous studies have supported the claim that psychological stress induces the production of reactive oxygen species. Several authors have suggested that patients with psychiatric disorders show high levels of oxidative stress markers. We examined different oxidative stress markers in patients with chronic schizophrenia.Methods: This study included 29 patients with chronic schizophrenia and 30 healthy volunteers. The concentration of urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG), as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. Psychiatric symptoms were assessed by the administration of the Brief Psychiatric Rating Scale (BPRS).Results: The concentration of biopyrrins in patients with chronic schizophrenia was significantly higher when compared with healthy volunteers. The correlation between biopyrrin level and the duration of illness was highly significant. There were no significant differences in the levels of urinary 8-OHdG between the two groups. In schizophrenic patients, the level of urinary biopyrrins showed correlations with BPRS scores, while the level of urinary 8-OHdG did not show correlations with BPRS.Conclusions: Urinary biopyrrins are increased in patients with chronic schizophrenia while urinary 8-OHdG is not increased. These findings suggest that patients with chronic schizophrenia are under the condition of certain oxidative stresses.

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Yi-gan san may be an effective and safe therapy to control visual hallucination in patients with CBS and should be further tested in double-blind, placebo-controlled trials. Given the design characteristics of this trial, the present findings should be taken cautiously.