Maiko Hayashida

Possible antipsychotic effects of minocycline in patients with schizophrenia

We present two cases of patients with schizophrenia treated with minocycline. Minocycline (a second-generation tetracycline) is an established and safe broad-spectrum antibiotic that crosses the blood-brain barrier, with additional efficacy for diseases such as acne and rheumatoid arthritis. Animal studies have suggested that minocycline may prevent progression of some neurological disorders. Moreover, it has been reported that minocycline might have antidepressant effects. We report two cases of acute schizophrenia with predominant catatonic symptoms that responded to minocycline.

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.

Factors disturbing treatment for cancer in patients with schizophrenia

Abstract  Patients with schizophrenia who develop cancer often have a variety of complicated medical and psychiatric problems. Problems associated with receiving a diagnosis of cancer and with understanding or cooperating with medical treatment may develop. Research in managing and treating schizophrenia patients with cancer is scarce. Presented herein is the experience of the authors’ consultation–liaison psychiatry service in treating patients with schizophrenia who have cancer, and discussion of the medical management of such cases. Fourteen patients were treated between April 1999 and March 2003 and included patients receiving consultation psychiatric services at Shimane University Hospital as well as patients referred from other psychiatric hospitals. These patients were divided into two groups based on whether they were amenable to cancer treatment or not. The treated group consisted of patients who accepted cancer treatment, and the untreated group consisted of patients who refused or interrupted the cancer treatment. The clinical course, clinical psychiatric symptoms, problems in understanding cancer, cancer treatment course and convalescence were retrospectively assessed. Psychiatric symptoms and state were measured using the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). The mean of the duration of schizophrenia in these two groups was not significantly different. The mean scores on measures of psychiatric symptoms in each group (treated and untreated) were as follows: BPRS, 45.3 ± 15.4 and 64.9 ± 9.2 (P < 0.05); positive symptoms scores on PANSS, 14.4 ± 8.8 and 20.6 ± 6.0 (NS); negative symptoms scores on PANSS, 20.6 ± 4.7 and 33.6 ± 4.4 (P < 0.01); and total scores on PANSS, 31.7 ± 7.0 and 48.6 ± 7.4 (P < 0.01). Patients with severe negative symptoms had greater difficulty understanding and cooperating with the cancer treatment. Regarding cancer stage, when cancer was discovered, the disease had already advanced and was no longer amenable to first‐line treatment. Regarding notification of the diagnosis, it was rarely possible to give sufficiently early notice to patients in the untreated group. The important role of consultation–liaison psychiatrist in treating cancer patients is suggested. Some steps are proposed for managing schizophrenia patients with cancer who are not able to give informed consent.

Hyperbilirubinemia-related behavioral and neuropathological changes in rats: A possible schizophrenia animal model

BACKGROUND Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and the general healthy population. We examined the hyperbilirubinemia on behavioral and neuropathological changes in rats as a possible animal model of schizophrenia. METHODS Gunn rats with severe hyperbilirubinemia (j/j), Gunn rats without severe hyperbilirubinemia (+/j), and Wistar rats were examined by open-field, social interaction, and prepulse inhibition tests. TUNEL, AgNOR and Ki-67 were also assayed on paraffin-embedded brain sections of these rats. RESULTS Compared to Wistar rats, both Gunn j/j and +/j rats showed hyperlocomotion, high sniffing scores, and low defecation scores. They showed significantly more aggressive behaviors and impaired prepulse inhibition. The numbers of Ki-67-labeled cells and AgNOR were lower and the number of TUNEL-positive cells was higher than that of Wistar rats. CONCLUSIONS These results might support the neurodevelopmental hypothesis of schizophrenia. Both Gunn j/j and +/j rats may be a useful animal model and provide clues to the role of hyperbilirubinemia in schizophrenia.

High salivary alpha-amylase levels in patients with schizophrenia: A pilot study

Previous studies have demonstrated the autonomic dysregulation in patients with schizophrenia using electrophysiological methods, such as electrodermal measures and heart rate analysis. Several theories have been proposed to explain the underlying mechanisms of schizophrenia and its autonomic function. Recently, the measurement of salivary alpha-amylase has been considered to be a useful tool for evaluating the sympathetic-adrenal-medullary (SAM) system. Psychosocial stress increases the release of salivary alpha-amylase. Although some studies have evaluated salivary alpha-amylase under psychosocial stress, no studies have demonstrated the change in the salivary alpha-amylase (sAA) activity level in schizophrenic patients. We examined the relationship between sAA level and psychiatric state in patients with schizophrenia (n=54) using a portable and rapid hand-held monitor to investigate sAA. The sAA activity in the patients was significantly higher than that in the control subjects (n=55) (p<0.01). The correlation between amylase level and psychiatric symptoms was highly significant (r=0.37, p<0.01). These findings indicate that higher increases in sAA may indicate severe psychiatric symptoms. These results indicate a predominant role of the sympathetic nervous system in the secretion of sAA, together with parasympathetic withdrawal, under psychosocial stress.

Increased urinary excretion of biopyrrins, oxidative metabolites of bilirubin, in patients with schizophrenia

During periods of psychological stress, excess amounts of free radicals are produced, and they play an important role in the pathophysiological process. Bilirubin oxidative metabolites, biopyrrins, are generated from bilirubin as a result of this scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrin is altered during the psychotic state in patients with schizophrenia. Biopyrrin concentrations in urine of 15 patients with schizophrenia and 100 age-matched healthy subjects were measured by enzyme-linked immunosorbent assay with an anti-bilirubin antibody. Urine samples were obtained from the patients on first admission (acute state), 1 month after admission (sub-acute state), and on discharge (remission state). Urinary concentrations of biopyrrins in patients with schizophrenia on admission were significantly higher than those in the controls. Response to treatment was associated with a significant decrease in the concentrations of biopyrrins. Moreover, urinary concentrations of biopyrrins were still significantly higher in patients with schizophrenia in the sub-acute and remission states than in the controls. These results demonstrated an increase in urinary biopyrrins in patients with schizophrenia and a decrease with recovery from the psychotic state. These findings indicate that the urinary biopyrrin level is a possible indicator that can be useful in the continuous monitoring of psychotic states in clinical practice.

Charles Bonnet syndrome: Successful treatment of visual hallucinations due to vision loss with Yi-gan san

Visual hallucination is a common (10–15% prevalence) and often distressing consequence of vision loss, particularly in age-related macular degeneration (for review see Rovner, 2006). Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration and preserved cognitive status. The strongest risk factors for CBS are bilateral visual system impairment, declining visual acuity, cerebral damage, cognitive defects, social isolation and sensory deprivation (Menon, 2005). So far, although this condition is frequent, no established treatment for CBS has been stated in the literature. Neuroleptics, particularly atypical ones with high amount of serotonergic activity, have been proven to be effective in single cases (Moja et al., 2005). Yi-gan san (YGS, yokukan-san in Japanese) was developed in 1555 by Xue Kai as a remedy for restlessness and agitation in children (Aizawa et al., 2002). It was reported a fewmild and transient adverse events, including headache, nausea, tiredness, and hypokalemia. Iwasaki et al., (2005) reported that YGS improved BPSD and activities of daily living in a randomized, observer-blind, control trial. Moreover, we reported that YGS therapy is a well-tolerated and effective remedy that improves the symptoms of some psychiatric disorder (Miyaoka et al., 2008a,b,in press). Depending on the traditional Japanese medicine studied, those detailed case observations and clinical trials can offer hints at new treatments for CBS. To our knowledge there have been no prior reports of its efficacy, or the efficacy of YGS in the treatment of CBS.

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.

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.