Tomoko Araki

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.

Evaluation of autonomic nervous system by salivary alpha-amylase level and heart rate variability in patients with 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.

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.

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.

Ramelteon as adjunctive therapy for delirium referred to a consultation‐liaison psychiatry service: a retrospective analysis

Delirium is one of the most common and serious mental disorders of attention and cognition, with high morbidity, mortality, and healthcare costs. Although the pathology of delirium remains unclear, delirium is generally treated with antipsychotics, which have occasionally induced serious adverse events. Ramelteon is an agonist of melatonin receptor that is used to treat insomnia. We reported a case series that adjunctive ramelteon with antipsychotics successfully treated delirium (Furuya et al., 2012). We hypothesized that adjunctive ramelteon with antipsychotics would be more effective for delirium than antipsychotics monotherapy.

Efficacy and Safety of Sansoninto in Insomnia with Psychiatric Disorder: AnOpen-Label Study

Background: Prior research confirms that insomnia is highly prevalent in patients with psychiatric disorders. Benzodiazepine hypnotics, causing serious disadvantages, have been widely used in psychiatry for a long time. Sansoninto (SNT), Japanese herbal medicine, is used for patients with weakness and fatigue, annoyance, insomnia, amnesia, and neurotic symptoms. Objective: The efficacy and safety of SNT was examined in adult psychiatric disorder patients with insomnia symptoms. Methods: Eighty-one adults with sleep disturbance meeting DSM-IV-TR diagnostic criteria for psychiatric disorders (schizophrenia: 17; monopolar depression: 20; bipolar depression: 10; adjustment disorder: 12; anxiety disorder: 5; others: 17) were treated openly for four weeks with SNT (2.5-7.5 g) at bedtime. Patients maintained sleep throughout the study. Efficacy was analyzed using a repeated measures methodology. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes were the Insomnia Severity Index (ISI), Athens Insomnia Scale (AIS), Clinical Global Impression-Improvement (CGI-I), and change of dosage of benzodiazepine hypnotics (diazepam equivalent). Results: After 4 weeks of SNT therapy, significant symptom reduction was observed on all parameters (PSQI: 10.22 ± 3.23 vs. 3.11 ± 3.52; ISI: 20.63 ± 4.86 vs. 3.38 ± 5.10; AIS: 17.41 ± 4.69 vs. 2.85 ± 4.23; dosage of benzodiazepine hypnotics [diazepam equivalent, mg]:10.5 ± 4.71 vs. 2.98 ± 3.37). No withdrawal involved treatmentrelated adverse events. Conclusion: Data from this 4-week open-label study suggests SNT was an effective and generally well tolerated treatment for insomnia symptoms in this sample of adult patients with psychiatric disorders.

Analysis of oxidative stress expressed by urinary level of biopyrrins and 8-hydroxydeoxyguanosine in patients with chronic schizophrenia.

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.

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia‐like behavior.

Remission of Psychosis in Treatment-Resistant Schizophrenia following Bone Marrow Transplantation: A Case Report

The authors present the case of a 24-year-old male with treatment-resistant schizophrenia, with predominant severe delusion and hallucination, who received bone marrow transplantation (BMT) for acute myeloid leukemia. After BMT, he showed a remarkable reduction in psychotic symptoms without administration of neuroleptics. He also showed drastic improvement in social functioning. Follow-up evaluations 2 and 4 years after BMT showed persistent significant improvement of the psychotic state and social functioning. Recent findings show that the major underlying pathogenic mechanism of schizophrenia is immune dysregulation. Thus, conceptually, BMT, a cellular therapy, that facilitates the counteractive processes of balancing inflammation by immune regulation, could produce beneficial clinical effects in patients with treatment-resistant schizophrenia. Further studies are required to define the true benefits of BMT for the possible curative treatment of schizophrenia.

Cognitive Behavioral Therapy for Insomnia as Adjunctive Therapy to Antipsychotics in Schizophrenia: A Case Report

The authors present the case of a 38-year-old man with schizophrenia and with severe insomnia, who attempted suicide twice during oral drug therapy with risperidone. The patient slept barely 2 or 3 h per night, and he frequently took half days off from work due to excessive daytime sleepiness. As a maladaptive behavior to insomnia, he progressively spent more time lying in bed without sleeping, and he repeatedly thought about his memories, which were reconstructed from his hallucinations. His relatives and friends frequently noticed that his memories were not correct. Consequently, the patient did not trust his memory, and he began to think that the hallucinations controlled his life. During his insomniac state, he did not take antipsychotic drugs regularly because of his irregular meal schedule due to his excessive daytime sleepiness. The authors started cognitive behavioral therapy for insomnia (CBT-i) with aripiprazole long acting injection (LAI). CBT-i is needed to be tailored to the patients specific problems, as this case showed that the patient maladaptively use chlorpromazine as a painkiller, and he exercised in the middle of the night because he believed he can fall asleep soon after the exercise. During his CBT-i course, he learned how to evaluate and control his sleep. The patient, who originally wanted to be short sleeper, began to understand that adequate amounts of sleep would contribute to his quality of life. He finally stopped taking chlorpromazine and benzodiazepine as sleeping drugs while taking suvorexant 20 mg. Through CBT-i, he came to understand that poor sleep worsened his hallucinations, and consequently made his life miserable. He understood that good sleep eased his hallucinations, ameliorated his daytime sleepiness and improved his concentration during working hours. Thus, he was able to improve his self-esteem and self-efficacy by controlling his sleep. In this case report, the authors suggest that CBT-i can be an effective therapy for schizophrenia patients with insomnia to the same extent of other psychiatric and non-psychiatric patients.