Motohide Furuya

Yi-gan san for the treatment of borderline personality disorder: an open-label study.

BACKGROUND Numerous medications have been tested on patients with borderline personality disorder (BPD). Although many of these medications have been demonstrated to be useful, no clear main treatment for BPD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Chinese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in dementia patients. We aimed at evaluating both efficacy and safety of yi-gan san in patients with well-defined BPD. METHODS Twenty female outpatients diagnosed with BPD according to DSM-IV criteria and the revised Diagnostic Interview for Borderlines completed a 12-week open-label study with yi-gan san at an average daily dosage of 6.4+/-1.9 g (2.5-7.5 g). Psychometric instruments to assess efficacy included the Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scales for Depression (HAM-D), Global Assessment of Functioning (GAF), Clinical Global Impression Scale (CGI), and Aggression Questionnaire (AQ). RESULTS Most psychometric scale scores exhibited a highly significant improvement (total BPRS; BPRS somatic concern, anxiety, tension, depressive mood, hostility, suspiciousness, motor retardation, uncooperativeness, and excitement subscale; CGI; GAF; AQ) over time. CONCLUSIONS In this open-label pilot study, patients treated with YGS showed statistically significant reduction on self-rated and clinician-rated scales. The present findings suggest that yi-gan san might be effective for the treatment of a number of BPD symptoms, including low mood, impulsivity, and aggression.

Yi-gan san as adjunctive therapy for treatment-resistant schizophrenia: an open-label study.

Backgroud: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS; yokukan-san in Japanese) may be safe and useful in treating behavioral and psychological symptoms in patients with dementia and borderline personality disorder. We aimed at evaluating both the efficacy and safety of YGS in patients with treatment-resistant schizophrenia. Methods: Thirty-four patients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (YGS-free) group (n = 25) and treated in a 4-week open-label study with YGS at an average daily dosage of 6.7 ± 2.5 g (range, 2.5-7.5 g). Psychometric instruments used to assess efficacy included the Positive and Negative Syndrome Scale for Schizophrenia and the Drug-Induced Extrapyramidal Symptom Scale. Results: A significant decrease was observed at 2 weeks and at 4 weeks in each Positive and Negative Syndrome Scale for Schizophrenia subscale score in the YGS group, but this was not observed in the control group. However, the Drug-Induced Extrapyramidal Symptom Scale total score did not change in both groups. Conclusions: In this open-label pilot study, patients treated with YGS showed a statistically significant reduction on clinician-rated scales. The present findings suggest that an adjunction of YGS might be effective for treatment-resistant schizophrenia.

Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: an open-label study.

BACKGROUND Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese), a serotonin modulator, may be safe and useful in treating behavioral and psychological symptoms in dementia and borderline personality disorder patients. The authors examined the efficacy, tolerability, and safety of YGS in patients with tardive dyskinesia. METHODS Twenty-two patients with schizophrenia who had neuroleptic-induced tardive dyskinesia were given 7.5 g/day of YGS for 12 weeks in an open-label study. RESULTS Administration of YGS resulted in a statistically significant improvement in tardive dyskinesia and psychotic symptoms. CONCLUSIONS YGS may be an effective and safe therapy to control tardive dyskinesia and psychosis in patients with schizophrenia, that should be further tested in double-blind, placebo-controlled trials.

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

BackgroundSchizophrenia 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.MethodsUsing 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.ResultsWe 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.ConclusionsWe 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.

Marked improvement in delirium with ramelteon: five case reports

Delirium is a common and serious acute neuropsychiatric syndrome characterized by inattention and global cognitive dysfunction. Delirium is associated with higher morbidity, higher mortality and longer hospitalization, but its aetiology remains unclear. We successfully treated five cases of delirium within 1 day with ramelteon, a novel selective melatonin receptor agonist. This suggests that correction of the circadian rhythm disturbance, one of the main symptoms of delirium, plays a crucial role in its treatment and sheds new light on a therapeutic strategy for treatment of delirium.

Minocycline improves recognition memory and attenuates microglial activation in Gunn rat: A possible hyperbilirubinemia-induced animal model of schizophrenia

BACKGROUND Accumulating evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. We previously reported evidence of schizophrenia-like behaviors and microglial activation in Gunn rats. We concluded that the Gunn rat, which exhibits a high concentration of unconjugated bilirubin, may be useful as an animal model of schizophrenia. On the other hand, there have been numerous reports that minocycline is effective in treating schizophrenia. METHODS In the present study, we investigated the effects of minocycline on performance of behavioral tests (prepulse inhibition (PPI) and novel object recognition test (NORT)) after animals received either 40mg/kg/d of minocycline or vehicle by intraperitoneal (i.p.) injection for 14 consecutive days. Furthermore, we examined the effects of minocycline on microglial activation in the hippocampal dentate gyrus of Gunn rats and Wistar rats. RESULTS We found that administration of minocycline for 14days significantly increased the exploratory preference in retention sessions and tended to improve the PPI deficits in Gunn rats. Immunohistochemistry analysis revealed that microglial cells in the minocycline-treated Gunn rat group showed less expression of CD11b compared to vehicle-treated Gunn and Wistar groups. CONCLUSIONS Our findings suggest that minocycline improves recognition memory and attenuates microglial activation in the hippocampal dentate gyrus of Gunn rats. Therefore, minocycline may be a potential therapeutic drug for schizophrenia.

The effects of combine treatment of memantine and donepezil on Alzheimer's Disease patients and its relationship with cerebral blood flow in the prefrontal area

In this study, we evaluated the effect on cognitive function of memantine, behavioral and psychological symptoms of dementia, and the care burden, in patients with moderate‐to‐severe Alzheimers disease (AD). Furthermore, with near‐infrared spectroscopy (NIRS), we examined the association between effect of memantine and brain blood flow.

Yokukansan promotes hippocampal neurogenesis associated with the suppression of activated microglia in Gunn rat

BackgroundThe pathophysiology of schizophrenia (SCZ) remains unclear, and its treatment is far from ideal. We have previously reported that yokukansan (YKS), which is a traditional Japanese medicine, is effective as an adjunctive therapy for SCZ. However, the mechanisms underlying the action of YKS have not yet been completely elucidated. A recent meta-analysis study has shown that adjuvant anti-inflammatory drugs are effective for SCZ treatment, and it has been proposed that some of the cognitive deficits associated with inflammation may in part be related to inflammation-induced reductions in adult hippocampal neurogenesis. Although certain ingredients of YKS have potent anti-inflammatory activity, no study has determined if YKS has anti-inflammatory properties.MethodsUsing the Gunn rat, which has been reported as a possible animal model of SCZ, we investigated whether YKS affects cognitive dysfunction in an object-location test and the suppression of microglial activation and neurogenesis in the hippocampus.ResultsWe found that YKS ameliorated spatial working memory in the Gunn rats. Furthermore, YKS inhibited microglial activation and promoted neurogenesis in the hippocampal dentate gyrus of these rats. These results suggest that the ameliorative effects of YKS on cognitive deficits may be mediated in part by the suppression of the inflammatory activation of microglia.ConclusionsThese findings shed light on the possible mechanism underlying the efficacy of YKS in treating SCZ.

Glia: an important target for anti-inflammatory and antidepressant activity.

Activated glial cells are capable of generating various inflammatory mediators, including cytokines, nitric oxide and reactive oxygen species. These potentially neurotoxic molecules have been suggested to play a role in the etiology and development of depression. Accumulating evidence indicates that antidepressants have inhibitory effects on inflammatory activation of glial cells and confer neuroprotection under neuropathological conditions. Such efficacy of antidepressants appears to depend on suppressing microglial production of inflammatory substances and up-regulating both astrocytic secretion of neurotrophins and astrocytic glutamine synthase, which converts neurotoxic glutamate into non-toxic glutamine. Therefore, glial cells, both as source and target of inflammatory molecules, may represent a potential promising target involved in the pathophysiology of depression. Moreover, antidepressants have the possibility to be useful treatment, not only for depression, but for a broad spectrum of neuroinflammatory and neurodegenerative disorders where the pathogenesis is associated with glial activation.

Yi-gan san for treatment of charles bonnet syndrome (visual hallucination due to vision loss): an open-label study.

Background:Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful for treating behavioral and psychological symptoms in dementia, borderline personality disorder, neuroleptic-induced tardive dyskinesia, and treatment-resistant schizophrenia. Visual hallucinations are common and often distressing consequences of vision loss, particularly in age-related macular degeneration. Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration, and preserved cognitive status. We aimed at evaluating both the efficacy and safety of YGS in patients with CBS. Methods:Twenty patients diagnosed with CBS were investigated, according to the diagnostic criteria established by Gold and Rabins and Teunisse. Participants were treated in a 4-week open-label study with YGS at an average daily dose of 5.8 ± 2.6 g (2.5-7.5 g). Psychometric instruments used to assess efficacy included the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression. No cases of serious adverse events were attributed to the studys drug therapy. Results:A significant decrease in visual hallucination was observed at 2 and 4 weeks in the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression scores. Conclusions: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.