Tsuyoshi Miyaoka

CSF iron, ferritin and transferrin levels in restless legs syndrome.

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age‐matched patients of psychophysiological insomnia without RLS symptoms (non‐RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non‐RLS group. Periodic leg movement index in the RLS group was higher than that of the non‐RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non‐RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non‐RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.

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.

Prevalence of restless legs syndrome in non- institutionalized Japanese elderly

Abstract  The purpose of the present paper was to evaluate the prevalence of restless legs syndrome (RLS) in a non‐institutionalized Japanese elderly population. The subjects consisted of 8900 elderly people >65 years of age belonging to the Seniors Association in Izumo City in November 2000. The present study was conducted in two parts. The phase 1 investigation was a screening by mailed questionnaire and the phase 2 investigation was diagnosis by face‐to‐face interview. Subjects with possible cases of RLS in phase 1 proceeded to phase 2 and definite cases of RLS were then detected. In phase 1, a total of 3287 subjects completely answering all questionnaire items, were defined as the subjects of the present study. A total of 150 were classified as having ‘probable RLS’, resulting in a prevalence of 4.6%. These subjects with probable RLS in phase 1 were detected as the subjects of phase 2. By face‐to‐face interview and various clinical examinations, a total of 35 subjects (nine male, 26 female) were diagnosed as having definite RLS, resulting in a prevalence of 1.06%. Furthermore, seven subjects (two male, five female) with symptomatic RLS were detected and finally 28 subjects (seven male, 21 female) were diagnosed as having idiopathic RLS. It was significantly higher in women for both the total and idiopathic RLS groups (0.60% male vs 1.46% female; 0.46% male vs. 1.18% female, respectively). The prevalence of RLS may be lower in the Japanese elderly than that in Caucasian subjects. These results could enhance understanding of the differences in predisposition between the races.

Sleep disturbances and depression in the elderly in Japan

Abstract The purpose of the present study was to evaluate the relationship between sleep disturbances and depression in the Japanese elderly. Methods: These investigations in the Japanese elderly were carried out with the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index, and questions on restless legs syndrome and nocturnal eating disorder. A total of 2023 people (male: 1008; female: 1015; average age: 74.2 ± 6.3 years) were analyzed by χ2 test and simple and multiple logistic regression. The prevalence of sleep disturbance was 37.3% and that of depression was 31.3%. Female gender and/or older (≥75 years) age were significantly associated with depression. Characteristics in depressive elderly were poor sleep efficiency, sleep disturbances due to difficulty of initiating sleep (DIS), breathing discomfort, coldness and pain, poor subjective sleep quality and lack of enthusiasm for activities. Sleep disturbances due to using the bathroom, breathing discomfort and coldness and long sleep latency were associated with depression in younger (65–74 years) men. Sleep disturbance due to DIS was associated with depression in older (≥75 years) men. Sleep disturbance due to pain was associated with depression in younger and older women. Poor sleep efficiency was associated with depression in older women. Poor subjective sleep quality was associated with depression in younger and older men and younger women. Lack of enthusiasm was associated with depression in younger and older men and older women. Restless legs syndrome was statistically significantly associated with depression in younger men. It is concluded that sleep disturbance and depression among the Japanese elderly are closely related symptoms. The features of sleep disturbance with depression differed with sex and age.

A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease.

BACKGROUND AND PURPOSE The cognitive decline in Alzheimers disease (AD) patients has been reported to involve alterations in the medial temporal lobe and the posterior cingulate gyrus. On the other hand, the neurochemical pathologies of the behavioral and psychological symptoms of dementia (BPSD) have not been sufficiently discussed. The aim of this study was to clarify the pathologies of BPSD in AD patients. METHODS Thirty patients with probable AD were included and underwent the following assessments: Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Story Recall Test (SRT), Behavioral pathology in Alzheimers disease (BEHAVE-AD) and proton MRS ((1)H-MRS). None of them had been medicated for BPSD. RESULTS The MRS study revealed that MMSE, CDT, and SRT scores were positively related to N-acetyl-aspartate (NAA)/creatine(Cr) and negatively related to myoinositol (mI)/Cr in the posterior cingulate gyrus, but not in the anterior cingulate gyrus. On the other hand, the scores obtained in two categories of BEHAVE-AD (delusional thought/ activity disturbances) were negatively related with NAA/Cr and positively related with mI/Cr in the anterior cingulate gyrus, but not in the posterior cingulate gyrus. CONCLUSION We conclude that BPSD and the decline in cognitive function in AD might have separate pathologies.

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.

Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases in patients with psychiatric disorders

Several authors have suggested that psychological stress induces the production of reactive oxygen species (ROS). Several studies have supported the idea that bilirubin exerts antioxidative effects in vivo, and it was reported psychological stress provokes bilirubin oxidation in vivo [Yamaguchi T., Shioji I., Sugimoto A., Yamaoka M., 2002. Psychological stress increases bilirubin metabolites in human urine. Biochem. and Biophys. Res. Commun. 293, 517-520]. We investigated whether the concentration of bilirubin oxidative metabolites (biopyrrins) is increased in urine from patients with psychiatric disorders. The concentration of biopyrrins in urine of 25 patients with psychiatric disorders (schizophrenia, 15; depression, 10) was compared with 96 healthy volunteers. The concentrations of biopyrrins, as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. The concentration of biopyrrins in patients with psychiatric disorders (schizophrenia and depression) was significantly higher than that of healthy volunteers. In schizophrenia, biopyrrins levels correlated with scores of the Brief Psychiatric Rating Scale (BPRS), and in depression, biopyrrins levels correlated with scores of the Hamilton Depression Rating Scale (HAM-D). These finding suggest that psychotic states are associated with an increase in the oxidative metabolites of bilirubin in human urine.

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.

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

OBJECTIVE Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. DATA SOURCES Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. STUDY SELECTION AND DATA EXTRACTION Publications relevant to the objective of this article were obtained (1992-2010), and some adverse neuropsychiatric reactions were summarized. DATA SYNTHESIS Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. CONCLUSIONS Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem.