Itaru Miura

Three-year trend survey of psychological distress, post-traumatic stress, and problem drinking among residents in the evacuation zone after the Fukushima Daiichi Nuclear Power Plant accident [The Fukushima Health Management Survey].

Prolonged periods of instability in terms of living environment can lead to a serious increase in mental health issues among disaster‐affected individuals. The aim of this study was to assess long‐term trends in mental health among adult residents in a nuclear‐disaster‐affected area.

Effects of aripiprazole and the Taq1A polymorphism in the dopamine D2 receptor gene on the clinical response and plasma monoamine metabolites level during the acute phase of schizophrenia.

Abstract The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene could be related to the response to antipsychotics. We examined the effects of the Taq1A polymorphism on the plasma monoamine metabolites during the treatment of schizophrenia with aripiprazole, a DRD2 partial agonist. Thirty Japanese patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol (pMHPG) before and after treatment. The Taq1A polymorphism was genotyped with polymerase chain reaction. Aripiprazole improved the acute symptoms of schizophrenia and decreased pHVA in responders (P = 0.023) but not in nonresponders (P = 0.28). Although A1 allele carriers showed a tendency to respond to aripiprazole (61.5%) compared to A1 allele noncarriers (29.4%) (P = 0.078), there was not statistically significant difference in the response between the 2 genotype groups. There were significant effect for response (P = 0.013) and genotype × response interaction (P = 0.043) on the change of pHVA. The changes of pHVA differ between responders and nonresponders in A1 allele carriers but not in A1 allele noncarriers. There were no genotype or response effects or genotype × response interaction on the changes of the plasma levels of 3-methoxy-4hydroxyphenylglycol. Our preliminary results suggest that Taq1A polymorphism may be partly associated with changes in pHVA during acute schizophrenia.

Elevated postmortem striatal t-DARPP expression in schizophrenia and associations with DRD2/ANKK1 polymorphism.

BACKGROUND Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN) have been implicated in the pathogenesis of schizophrenia because they function as molecular integrators of dopamine and glutamate signaling. DARPP-32 and CaN are mainly expressed in the caudate nucleus and putamen; however, a few postmortem brain studies have focused on DARPP-32 expression in striatum from patients with schizophrenia. METHODS We used immunoblotting techniques and postmortem tissue samples from patients with schizophrenia and from normal control individuals to examine the expression of two major DARPP-32 isoforms, full-length (FL-DARPP) and truncated (t-DARPP), and of CaN in the striatum. We also assessed whether there was any significant correlation between the expression levels of either protein and the A1 allele of Taq1A genotype in the dopamine D2 receptor (DRD2) gene/ankyrin-repeat containing kinase 1 (ANKK1) gene. RESULTS We found that the mean t-DARPP expression level in the caudate was higher in patients with schizophrenia than in control individuals (P<0.05) and the A1 allele of Taq1A genotype in DRD2/ANKK1 was significantly associated with elevated expression of t-DARPP in the caudate. Also, the A1 allele was significantly correlated with the total score of antemortem psychiatric symptoms. CONCLUSION These results may reflect potential molecular mechanisms important to the pathogenesis of schizophrenia.

Reduced brain activity in female patients with non-alcoholic fatty liver disease as measured by near-infrared spectroscopy

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired health-related quality of life including physical and mental state. Near-infrared spectroscopy (NIRS) is a useful tool for evaluation of brain activity and depressive state. This study aimed to determine the brain activity of female NAFLD patients using NIRS. Cerebral oxygenated hemoglobin (oxy-Hb) concentration during a verbal fluency task (VFT) was measured using NIRS in 24 female NAFLD patients and 15 female healthy controls. The Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire was administered to both groups before NIRS. There was no significant difference in CES-D score between groups. However, the oxy-Hb concentration and number of words during the VFT were less in NAFLD compared to healthy controls. The mean value of oxy-Hb concentration during 0–60 s VFT in the frontal lobe was also smaller in NAFLD patients compared to healthy controls (0.082 ± 0.126 vs. 0.183 ± 0.145, P < 0.001). Cerebral oxygen concentration is poorly reactive in response to VFT in female NAFLD patients. This may indicate an association between decreased brain activity and NAFLD regardless of depression.

Influence of -141C Ins/Del Polymorphism in DRD2 Gene on Clinical Symptoms and Plasma Homovanillic Acid Levels in the Treatment of Schizophrenia With Aripiprazole.

FIGURE 1. Mean change in PANSS total (A), positive (B), negative (C), and plasmaHVA levels (D) of 2 genetic subgroups. There were no time genotype interactions on PANSS scores (total: P = 0.63, positive: P = 0.92, negative: P = 0.29) or plasma HVA levels (P = 0.61). B ecause the dopamine D2 receptor (DRD2) plays an important role in schizophrenia, genetic studies have been focused on this gene. A meta-analysis demonstrated a significant association between the −141C Ins/Del polymorphism in DRD2 and the response to antipsychotics, whereas the Taq1A polymorphism was not associated with the response. The −141C Ins/Del represents a deletion of cytosine at position −141, located in the 5′ promoter region of DRD2. The −141C Ins/Del polymorphism has effects on DRD2 density in the brain; however, the function of this polymorphism in schizophrenia remains unclear. Homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are major metabolites of dopamine and noradrenaline, respectively. In this study, we investigated the effect of the −141C Ins/Del polymorphism on clinical symptoms and plasma levels of HVA and MHPG during treatment with aripiprazole in antipsychoticfree patients with schizophrenia. Subjects were 34 Japanese patients (men, 22; women, 12; mean [SD] age, 41.2 [12.6] years) whose conditions were diagnosed with schizophrenia or schizoaffective disorder according to theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Thirty of 34 patients were the same subjects from our previous study, and a previous report contains detailed descriptions of the study design. The −141C Ins/Del genotype was determined with the polymerase chain reaction method as previously described. This study was approved by the ethics committee of FukushimaMedical University, and the patients consented to participate after having been informed of the purpose of the study. Student t test (unpaired) and Pearson χ test were used for comparisons between the 2 genotype groups. Student t test (paired) was used to compare measures from before and after the aripiprazole treatment. Analysis of variance with repeated measures was used to evaluate changes in the Positive and Negative Syndrome Scale (PANSS) score and

Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia

The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the models biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results.

Impacts of age on plasma monoamine metabolite concentrations in a large cohort of healthy individuals.

The measurement of plasma concentrations of monoamine metabolites is a useful method for inferring the dynamics of monoamine metabolites in the brain. To clarify effects of age and sex on plasma monoamine metabolites levels, we used high-performance liquid chromatography to measure plasma levels of homovanillic acid (HVA), free and total 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in healthy men and women of various ages (n=214). In all plasma monoamine metabolites, there were significant differences across the age groups, and multiple comparisons revealed that older subjects had higher levels than younger subjects. Moreover, significant positive correlations were found between age and plasma levels of HVA, free MHPG, total MHPG, and 5-HIAA. On the other hand, plasma concentrations of monoamine metabolites were not influenced by sex, except for total MHPG for which the plasma levels were significantly higher in men than in women. Age-related changes in monoamine oxidase and renal function might affect our results. This large cohort survey provides further evidence to be cautiously aware of age effects when regarding plasma monoamine metabolites levels as reflections of central activity.

Changes of Posttraumatic Stress Responses in Evacuated Residents and Their Related Factors: A 3-Year Follow-up Study From the Fukushima Health Management Survey

The longitudinal posttraumatic stress responses and resilient factors after the Fukushima Daiichi Nuclear Power Plant are yet unknown. Here we attempted to quantify the patterns of the course of posttraumatic stress disorder (PTSD) symptoms and we explored the factors associated with psychological recovery. The subjects were 12 371 residents in the municipalities categorized as the forced evacuated area. We categorized the subjects’ PTSD symptoms into 4 groups: Chronic, Resistant, Recovered, and Non-recovered. We applied a logistic regression to clarify the factors related to psychological recovery. We observed that laughter showed significant odds ratio in the Recovered group and the Resistant group. Meanwhile, elderly residents and those with poor living circumstances showed significant odds ratios for the Recovered group and the Resistant group. Laughter in daily life was associated with the psychological health in the evacuation area.

Effects of Shakuyaku-Kanzo-to on Extrapyramidal Symptoms During Antipsychotic Treatment: A Randomized, Open-Label Study.

Abstract Extrapyramidal symptoms (EPS) are common adverse effects of antipsychotic treatment. This study examined the effects of the traditional Japanese herbal medicine (kampo) shakuyaku-kanzo-to on EPS during antipsychotic treatment. Twenty-two Japanese patients with psychiatric disorders who had developed EPS during antipsychotic treatment were randomly allocated to receive either shakuyaku-kanzo-to (7.5 g/d) or biperiden (3 mg/d) for 2 weeks. Extrapyramidal symptoms were evaluated using the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) and the Barnes Akathisia Rating Scale. Plasma levels of the monoamine metabolite homovanillic acid and serum prolactin levels were measured to investigate the mechanisms of action of shakuyaku-kanzo-to. Twenty of the 22 patients completed the study (10 patients in the shakuyaku-kanzo-to group and 10 patients in the biperiden group). There was a time effect on the Drug-Induced Extrapyramidal Symptom Scale total score (P < 0.01), suggesting that both shakuyaku-kanzo-to and biperiden decreased EPS. Notably, there was a time × drug interaction in dystonia, suggesting that shakuyaku-kanzo-to had a greater effect on dystonia compared with biperiden. No significant changes were observed in plasma homovanillic acid or serum prolactin levels after 2 weeks of treatment in either group. The effects of shakuyaku-kanzo-to on abnormal muscle tonus and dopamine D2 receptors may have contributed to improve EPS. These results suggest that shakuyaku-kanzo-to may be useful in decreasing EPS, especially dystonia, in patients undergoing treatment with antipsychotic agents.

Near-infrared spectroscopy and plasma homovanillic acid levels in bipolar disorder: a case report.

Misdiagnosis of bipolar disorder is a serious, but not unusual problem for patients. Nevertheless, there are few biomarkers for distinguishing unipolar and bipolar disorder. Near-infrared spectroscopy (NIRS) is a noninvasive and useful method for the measurement of hemoglobin concentration changes in the cortical surface area, which enables the assessment of brain function. We measured NIRS and plasma monoamine metabolite levels in a patient with bipolar disorder. A 22-year-old man was admitted due to major depression. At admission, NIRS findings showed oxygenated hemoglobin reincrease in the posttask period, which is characteristic of schizophrenia. After treatment with paroxetine, he became manic with psychotic symptoms. His plasma level of homovanillic acid just before the manic switch was ten times higher than that just after paroxetine initiation. Treatment with lithium and antipsychotics was successful, and plasma homovanillic acid decreased after treatment. In this case, the NIRS findings may predict a possible risk of a manic switch, which is likely induced by paroxetine. NIRS may be able to help distinguish unipolar and bipolar disorder in clinical settings.