Hiroo Matsuoka

Reliability and validity of the Japanese version of the World Health Organization-Five Well-Being Index in the context of detecting depression in diabetic patients.

Abstract  The present study had two aims. The first was to evaluate the reliability and the validity of the Japanese version of the World Health Organization (WHO)‐Five Well‐Being Index (WHO‐5‐J) as a brief well‐being scale. The second was to examine the discriminatory validity of this test as a screening tool for current depressive episodes in diabetic patients. A sample of 129 diabetic patients completed the WHO‐5‐J. Of these, 65 were also interviewed by psychiatrists to assess whether they had any current depressive episodes according to DSM‐IV. The internal consistency was evaluated using Cronbach’s alpha, the Loevinger coefficient of homogeneity, and factor analysis. The external concurrent validity was evaluated by correlations with the external scales potentially related to subjective well‐being. Discriminatory validity was evaluated using receiver operating characteristic (ROC) analysis. Cronbach’s alpha and the Loevinger coefficient were estimated to be 0.89 and 0.65, respectively. A factor analysis identified only one factor. The WHO‐5‐J was significantly correlated with a number of major diabetic complications, depression, anxiety, and subjective quality of life. ROC analysis showed that the WHO‐5‐J can be used to detect a current depressive episode (area under curve: 0.92; 95% confidence interval: 0.85–0.98). A cut‐off of <13 yielded the best sensitivity/specificity trade‐off: sensitivity, 100%; specificity, 78%. The WHO‐5‐J was thus found to have a sufficient reliability and validity, indicating that it is a useful instrument for detecting current depressive episodes in diabetic patients.

Factors associated with suicidal ideation in an elderly urban Japanese population: A community‐based, cross‐sectional study

Abstract  The objective of the present study was to evaluate the association between suicidal ideation and potentially related factors in an elderly urban Japanese population. This was a community‐based, cross‐sectional study. Urban community residents aged 70 years or more were interviewed regarding suicidal ideation and sociodemographic and health‐related variables. Subjects with depressive symptoms underwent further evaluation by psychiatrists using criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Associations were evaluated using univariate and multivariate logistic regression analyses. Of the 1145 eligible participants, 52 (4.5%) reported thoughts of suicide. Of 143 subjects with depressive symptoms (Geriatric Depression Scale, 14+), 22 (15.4%) reported suicidal ideation over a 2‐week period. After controlling for depressive symptoms, lack of social support and impaired instrumental activities of daily living were significantly associated with thoughts of suicide. After controlling for the potentially associated factors detected in the univariate analysis, depressive symptoms were strongly associated with thoughts of suicide. In the elderly with depressive symptoms, mental disorders, including depressive and alcohol‐related disorders, were significantly associated with suicidal ideation over a 2‐week period. In the urban community setting, screening for lack of social support, impaired instrumental activities of daily living, and depressive symptoms, followed by diagnostic evaluation for mental disorders, particularly for depressive syndromes and alcohol‐related disorders, may provide a practical and effective means of identifying elders at high risk of suicide.

Cigarette smoking and the risk of gastric cancer: a pooled analysis of two prospective studies in Japan.

To examine the association between cigarette smoking and the risk of gastric cancer, we conducted a pooled analysis of 2 population‐based prospective cohort studies in rural northern Japan. Cohort 1 included 9,980 men (≥40 years old) and Cohort 2 included 19,412 men (40–64 years old). The subjects completed a self‐administered questionnaire on cigarette smoking and other health habits. We identified 228 cases of gastric cancer among Cohort 1 subjects (9 years of follow‐up with 74,073 person‐years) and 223 among Cohort 2 subjects (7 years of follow‐up with 141,675 person‐years). From each cohort, we computed the relative risk (RR) and 95% confidence interval (CI) of gastric cancer associated with smoking using a Cox regression analysis and pooled these estimates to obtain summary measures. The pooled multivariate RRs (95% CIs) for current smokers and past smokers compared to subjects who had never smoked were 1.84 (1.39–2.43) and 1.77 (1.29–2.43), respectively. The higher number of cigarettes smoked per day among current smokers was associated with a linear increase in risk (trend p < 0.05). The significant increase in risk for past smokers remained for up to 14 years after cessation. An increased risk was noted for cancer of the antrum but not for cardia or body lesions. The risk was increased for both differentiated and nondifferentiated histologic subtypes. Our findings support the hypothesis that cigarette smoking is a risk factor for gastric cancer.

Association between social support and depression status in the elderly: Results of a 1‐year community‐based prospective cohort study in Japan

Abstract  We conducted a prospective cohort study on subjects aged ≥ 70 years in an urban community to determine whether there is any association between lack of social support and depression status. Of the 2730 eligible subjects, 1178 participated and were interviewed in a Comprehensive Geriatric Assessment (CGA) in 2002. We investigated the five social supports items using the following questions: (i) do you have someone with whom you can consult when you are in trouble?, (ii) do you have someone with whom you can consult when your physical condition is not good?, (iii) do you have someone who can help you with your daily housework?, (iv) do you have someone who can take you to a hospital when you do not feel well?, and (v) do you have someone who can take care of you when you are ill in bed? The Geriatric Depression Scale was used to estimate depression status. The subjects were divided into two groups: depressive and non‐depressive. Of 753 subjects classified as non‐depressive, 475 also took part in a CGA in 2003 and 278 dropped out. We calculated the risk of depression status in the elderly without social support. Lack of social support items (i) and (v) were significantly associated with an increased risk of depression status. The multivariate odds ratios (95% confidence intervals) regarding the risk of depression status among the elderly without (i) and (v) social support items were 2.6 (1.2–5.3) and 3.0 (1.4–6.1), respectively. We also found the increase risk of depression status with lack of social support item (v) was significantly different for different sexes and for different pain conditions. We conclude that there is a significant increase in the risk of depression status associated with the lack of social support in Japanese elderly people in an urban community.

Methamphetamine alters expression of DNA methyltransferase 1 mRNA in rat brain.

Methamphetamine, a potent and indirect dopaminergic agonist, also increases glucocorticoid hormone secretion. Glucocorticoid hormones facilitate behavioral effects of methamphetamine in rodents. Several reports suggest that glucocorticoid hormones modulate expression of DNA (cytosine-5-)-methyltransferase 1 (Dnmt1). Dnmt1 was originally recognized as being involved in DNA replication, but a recent study found high levels of Dnmt1 in rodent brains, suggesting a neuron-specific unknown function of Dnmt1. In the present study, we found subchronic methamphetamine treatment (4 mg/kg, i.p., once daily for 21 days) to induce different patterns of Dnmt1 mRNA expression in the nucleus caudatus and nucleus accumbens of two inbred rat strains, Fischer 344/N (increased Dnmt1) and Lewis/N (decreased Dnmt1). These patterns paralleled methamphetamine-induced striatal glucocorticoid receptor mRNA in these two rat strains in our previous study. Because Fischer rats have a hyperresponsive negative feedback in their hypothalamic-pituitary-adrenocortical (HPA) axis and thus a shorter duration corticosterone response to subchronic methamphetamine treatment, they were resistant to sensitizing effects of methamphetamine and their glucocorticoid receptor mRNA levels were upregulated. Lewis rats which have a hyporesponsive feedback in their HPA axis and a longer duration of corticosterone secretion with subchronic methamphetamine were prone to methamphetamine sensitization and their striatal glucocorticoid receptor mRNA levels were downregulated. Our present data suggest that methamphetamine results in differential DNA methylation as well as gene expression in the nucleus caudatus and nucleus accumbens of F344 and Lewis rats. Methamphetamine-induced differences in gene expression might be related to the contrasting susceptibilities of these rats to behavioral and neurochemical effects of methamphetamine.

Saccadic eye movements in tracking, fixation, and rest in schizophrenic and normal subjects.

Horizontal eye movements were recorded electrooculographically during two different eye fixation tasks, during an eyes-closed waking state, and during eye tracking on a sinusoidally moving target in 16 chronic schizophrenics and in 12 normal subjects. The relationship between saccadic eye movements during tracking and in the other experimental situations was investigated. The intensities of eye fixation were successively decreased from Experiment I (eye fixation on a stationary target) through Experiment II (eye fixation on an imagined spot in the dark) to Experiment III (eyes closed in the dark, no cue for eye fixation), in that order. The frequency of saccades increased as the intensities of fixation decreased from Experiment I to Experiment III in both schizophrenic and normal groups. It was demonstrated that the frequency of saccades was higher in schizophrenics than in normal subjects in all of the experimental conditions. Some correlations were found between the increased frequency of saccades seen during eye tracking and the similar increases seen in eyes-fixated or eyes-closed states in schizophrenic subjects. It is suggested that the increased saccades seen during eye tracking and in other experimental conditions in schizophrenics are related to a deficit of nonvoluntary attention, due to a failure of an inhibitory mechanism.

Psychostimulant Alters Expression of DNA Methyltransferase mRNA in the Rat Brain

Abstract: Methamphetamine (MAP), the most frequently abused substance in Japan, causes severe drug dependence and psychosis, similar to schizophrenia. It is suggested that long‐term alterations in gene expression is related to MAP‐induced brain dysfunction, including dependence and psychosis. DNA (cytosine‐5) methyltransferase (Dnmt), a methylating enzyme of cytosine residues on CpG‐dinucleotides, plays an important role in X chromosome inactivation, genomic imprinting, and gene expression. Reelin is an extracellular matrix protein secreted by GABAergic interneurons. Heterozygous reeler mice that exhibit a 50% downregulation of reelin expression replicate the dendritic spine and GABAergic defects described in schizophrenia. DNA methylation plays an important role in the epigenetic modification of reelin expression. We previously found that MAP could alter expression of Dnmt1 mRNA in the rat brain. In this study, we examined the brain mRNA for Dnmt2 and reelin in MAP‐treated Wistar rats. Acute MAP (4 mg/kg) treatment significantly decreased Dnmt2 mRNA by 27% to 39% in hippocampus dentate gyrus, CA1, and CA3 24 h after treatment, and significantly decreased reelin mRNA by 28% in frontal cortex 3 h after treatment. These results suggest that (1) MAP can alter DNA methylation as well as expression of genes in these brain regions, and (2) decrease in reelin mRNA in the frontal cortex is similar to heterozygous reeler mice, which might be related to schizophrenia‐like psychotic symptoms of MAP psychosis.

Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients

Abstract  In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimers disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms.

Histamine H1 receptors in schizophrenic patients measured by positron emission tomography

Increasing evidence has shown that the histaminergic neuron system is implicated in the pathophysiology of schizophrenia. The aim of this study was to compare the distribution of histamine H1 receptors between schizophrenics and normal human subjects in vivo using positron emission tomography (PET). H1 receptor binding was measured in 10 normal subjects and 10 medicated schizophrenic patients by PET and [11C] doxepin, a radioligand for the H1 receptor. The binding potential (BP=Bmax/K(D)) of [11C] doxepin for available brain H1 receptors was calculated by a graphical analysis on voxel-by-voxel basis and compared between schizophrenics and normal subjects using the regions of interest (ROIs) and the statistical parametrical mapping (SPM99). BP values for H1 receptors in the frontal and prefrontal cortices and the cingulate gyrus were significantly lower among the schizophrenic patients than among the control subjects. On the contrary, there were no areas of the brain where H1 receptors were significantly higher among the schizophrenic patients than the control subjects. The results of our study suggest that the central histaminergic neuron system could be involved in the pathophysiology of schizophrenia, although further studies are needed to confirm this hypothesis.

Smooth pursuit eye movements and express saccades in schizophrenic patients

Abnormalities of saccades such as disinhibition have been hypothesized as one cause of smooth pursuit eye movement (SPEM) dysfunctions in schizophrenia. Thus, we studied saccadic eye movements in schizophrenics with SPEM dysfunction. Subjects were divided into three groups: 10 normal control subjects, 10 schizophrenic subjects without SPEM dysfunction and 10 schizophrenic subjects with SPEM dysfunction characterized by a cogwheel appearance. Visually guided saccades in gap and overlap paradigms (Saslow, 1967) were examined and saccadic reaction times (SRTs) were measured in all subjects. Only schizophrenics with SPEM dysfunctions tended to manifest excessive reflexive saccades, named express saccades (Fischer, 1987), in the gap paradigm. Moreover, most of them were also found to have express saccades in the overlap paradigm, whereas normal subjects and schizophrenic subjects without SPEM dysfunction did not show such phenomena under the same conditions. In particular, most express saccades in the overlap paradigm in schizophrenics with SPEM dysfunction, were found in movements to the right.