Association between vascular endothelial growth factor-mediated blood-brain barrier dysfunction and stress-induced depression.

Several lines of evidence suggest that stress induces the neurovascular dysfunction associated with increased blood-brain barrier (BBB) permeability, which could be an important pathology linking stress and psychiatric disorders, including major depressive disorder (MDD). However, the detailed mechanism resulting in BBB dysfunction associated in the pathophysiology of MDD still remains unclear. Herein, we demonstrate the role of vascular endothelial growth factor (VEGF), a key mediator of vascular angiogenesis and BBB permeability, in stress-induced BBB dysfunction and depressive-like behavior development. We implemented an animal model of depression, chronic restraint stress (RS) in BALB/c mice, and found that the BBB permeability was significantly increased in chronically stressed mice. Immunohistochemical and electron microscopic observations revealed that increased BBB permeability was associated with both paracellular and transcellular barrier alterations in the brain endothelial cells. Pharmacological inhibition of VEGF receptor 2 (VEGFR2) using a specific monoclonal antibody (DC101) prevented chronic RS-induced BBB permeability and anhedonic behavior. Considered together, these results indicate that VEGF/VEGFR2 plays a crucial role in the pathogenesis of depression by increasing the BBB permeability, and suggest that VEGFR2 inhibition could be a potential therapeutic strategy for the MDD subtype associated with BBB dysfunction.

Effects of CYP2D6 Genotypes on Venlafaxine Metabolism in Japanese Psychiatric Patients With Depression.

BACKGROUND: Venlafaxine (VEN) is primarily metabolized by CYP2D6. Although several studies have reported the significant effects of CYP2D6 on VEN and O-desmethylvenlafaxine (ODV) pharmacokinetics in Whites, limited data are available regarding the effects of the Asian-specific CYP2D6 genotype on VEN metabolism. This study evaluated the effects of the CYP2D6*10 and CYP2D6*5 genotypes on the steady-state plasma concentrations of VEN and ODV in Japanese patients. METHODS: This study included 75 Japanese patients with depression who were treated with VEN. Steady-state plasma concentrations of VEN and ODV were measured using liquid chromatography. Polymerase chain reaction was used to determine CYP2D6 genotypes. A stepwise multiple regression analysis was performed to analyze the relationship between independent variables (sex, age, smoking habit, and number of mutated alleles, CYP2D6*10 and CYP2D6*5), subject-dependent variables (plasma concentrations of VEN and ODV [all corrected for dose and body weight]), and the ODV/VEN ratio. RESULTS: Significant correlations were observed between the daily dose of VEN (corrected for body weight) and plasma concentrations of VEN (r = 0.498, P < 0.001) and ODV (r = 0.380, P = 0.001); ODV plasma concentrations were approximately 3.2 times higher than VEN plasma concentrations (VEN versus ODV = 18.60 ng/mL versus 59.10 ng/mL). VEN plasma concentrations (corrected for dose and body weight) did not differ with differing numbers of CYP2D6-mutated alleles. However, the ODV/VEN ratio decreased as the number of mutated CYP2D6 alleles increased (P = 0.001). CONCLUSIONS: This is the first study to examine the effects of CYP2D6*10 in a clinical setting. Although no effects on the plasma concentrations of VEN or ODV were observed, CYP2D6 polymorphism affects the ODV/VEN ratio. Further studies are needed to confirm the clinical relevance of these findings.

Comparison of physiological and behavioral responses to chronic restraint stress between C57BL/6J and BALB/c mice.

Rodent models of chronic restraint stress (CRS) are often used as simple models of depressive disorder. However, these models of stress have been mainly developed in rats, and the behavioral phenotypes of CRS models are still controversial. In this study, we compared the physiological and behavioral responses of C57BL/6J (B6) and BALB/c mice, which are commonly used in genetic and behavioral studies, to CRS. In addition to measuring physiological parameters and the levels of corticosterone (a stress hormone) in response to stress, we also examined changes in the levels of testosterone (an anti-stress hormone), which have rarely been studied in stressed mice. The mice were exposed to CRS for 6 h a day for 21 days. In both B6 and BALB/c mice, CRS elicited several physiological stress responses, including decreased body weight gain and changes in the tissue weights of stress-related organs. Accumulated corticosterone in the hair was measured, and BALB/c mice had significantly greater levels than control mice and B6 mice after CRS. On the other hand, in the case of accumulated testosterone in the hair, both B6 mice and BALB/c mice showed significantly higher concentrations than control mice, but the degree of change was not different between the two strains. In the sucrose preference test, BALB/c mice, but not B6 mice, showed anhedonia-like behavior after CRS. However, neither strain showed depressive-like behavior in the forced swim or tail suspension test. Our results show that the physiological and behavioral stress responses of BALB/c mice are greater than those of B6 mice, although anti-stress responses to CRS are similar in both strains. This suggests that BALB/c mice are likely to be advantageous for use as a CRS-induced depression model.

Construction of the common cortical space by spontaneous activity and its application in the mouse cortex.

Wide-field optical imaging of the animal brain is a useful technique for measuring brain dynamics, including spatial structure. However, quantitative inter-animal comparison is difficult due to lack of the common cortical space that can normalize individually imaged brains as done in human functional MRI studies. Here, by using wide-field functional Ca2+ imaging on anesthetized transgenic mice expressing G-CaMP7 in astrocytes and excitatory neutrons, we attempted to establish the common cortical space in mice, which can be useful as a standard of functional brain map. We initially reconstructed cortical areas embedded within spontaneous activity as the functional connectivity maps for the individual mice, then matched them in size, shape, and location across mice by geometric transformation. Finally, we assigned all the recorded signals into the transformed space, to make spatially normalized signals in the common cortical space. Using this method, we managed to extract activity patterns commonly observed across mice. These results suggest that the presented method is available to facilitate inter-animal comparison of brain dynamics, and has the potential to identify common brain activity across animals.

8-Hydroxylation and Glucuronidation of Mirtazapine in Japanese Psychiatric Patients: Significance of the Glucuronidation Pathway of 8-Hydroxy-Mirtazapine.

INTRODUCTION: To investigate the metabolism of mirtazapine (MIR) in Japanese psychiatric patients, we determined the plasma levels of MIR, N-desmethylmirtazapine (DMIR), 8-hydroxy-mirtazapine (8-OH-MIR), mirtazapine glucuronide (MIR-G), and 8-hydroxy-mirtazapine glucuronide (8-OH-MIR-G). METHODS: Seventy-nine Japanese psychiatric patients were treated with MIR for 1-8 weeks to achieve a steady-state concentration. Plasma levels of MIR, DMIR, and 8-OH-MIR were determined using high-performance liquid chromatography. Plasma concentrations of MIR-G and 8-OH-MIR-G were determined by total MIR and total 8-OH-MIR (i. e., concentrations after hydrolysis) minus unconjugated MIR and unconjugated 8-OH-MIR, respectively. Polymerase chain reaction was used to determine CYP2D6 genotypes. RESULTS: Plasma levels of 8-OH-MIR were lower than those of MIR and DMIR (median 1.42 nmol/L vs. 92.71 nmol/L and 44.96 nmol/L, respectively). The plasma levels (median) of MIR-G and 8-OH-MIR-G were 75.00 nmol/L and 111.60 nmol/L, giving MIR-G/MIR and 8-OH-MIR-G/8-OH-MIR ratios of 0.92 and 59.50, respectively. Multiple regression analysis revealed that smoking was correlated with the plasma MIR concentration (dose- and body weight-corrected, p=0.040) and that age (years) was significantly correlated with the plasma DMIR concentration (dose- and body weight-corrected, p=0.018). The steady-state plasma concentrations of MIR and its metabolites were unaffected by the number of CYP2D6*5 and CYP2D6*10 alleles. DISCUSSION: The plasma concentration of 8-OH-MIR was as low as 1.42 nmol/L, whereas 8-OH-MIR-G had an approximate 59.50 times higher concentration than 8-OH-MIR, suggesting a significant role for hydroxylation of MIR and its glucuronidation in the Japanese population.

Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients With Depression.

BACKGROUND: Plasma concentrations of the S-enantiomer of citalopram were different between extensive and poor CYP2C19 metabolizers in healthy subjects and depressed patients. However, most studies applied dose-corrected concentrations. Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma drug concentrations in Japanese patients with depression. METHODS: Subjects in this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of escitalopram once a day. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were identified using polymerase chain reaction methods. RESULTS: There were no differences in the steady-state plasma concentrations of escitalopram or desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram) among CYP2C19 genotype groups. However, 1-way analysis of variance showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram but not in the dose-adjusted plasma concentration of desmethylescitalopram. Analysis of covariance including age, sex, and body weight showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram and the ratio of desmethylescitalopram to escitalopram. CONCLUSIONS: These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram.

Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis.

OBJECTIVE: Although the reduced function of the cytochrome P450 2D6*10 (CYP2D6*10) allele is common among Asian populations, existing evidence does not support paroxetine therapy adjustments for patients who have the CYP2D6*10 allele. In this study, we attempted to evaluate the degree of the impact of different CYP2D6 genotypes on the pharmacokinetic (PK) variability of paroxetine in a Japanese population using a population PK approach. METHODS: This retrospective study included 179 Japanese patients with major depressive disorder who were being treated with paroxetine. CYP2D6*1, *2, *5, *10, and *41 polymorphisms were observed. A total of 306 steady-state concentrations for paroxetine were collected from the patients. A nonlinear mixed-effects model identified the apparent Michaelis-Menten constant (Km) and the maximum velocity (Vmax) of paroxetine; the covariates included CYP2D6 genotypes, patient age, body weight, sex, and daily paroxetine dose. RESULTS: The allele frequencies of CYP2D6*1, *2, *5, *10, and *41 were 39.4, 14.5, 4.5, 41.1, and 0.6%, respectively. There was no poor metabolizer who had two nonfunctional CYP2D6*5 alleles. A one-compartment model showed that the apparent Km value was decreased by 20.6% in patients with the CYP2D6*10/*10 genotype in comparison with the other CYP2D6 genotypes. Female sex also influenced the apparent Km values. No PK parameters were affected by the presence of one CYP2D6*5 allele. CONCLUSION: Unexpectedly, elimination was accelerated in individuals with the CYP2D6*10/*10 genotype. Our results show that the presence of one CYP2D6*5 allele or that of any CYP2D6*10 allele may have no major effect on paroxetine PKs in the steady state.

The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients.

BACKGROUND: The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19. METHODS: Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration. RESULTS: Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 ± 36.9 ng/mL versus 135.2 ± 79.7 ng/mL, P < 0.01) but not those of desmethylescitalopram (21.5 ± 7.0 ng/mL versus 24.9 ± 12.0 ng/mL, no significance [ns]). The ratios of desmethylescitalopram to escitalopram were significantly decreased during fluvoxamine coadministration (0.37 ± 0.21 versus 0.21 ± 0.10, P < 0.01). The CYP2C19 genotype did not fully explain the degree of the change. Fluvoxamine coadministration did not change the QT or QTc intervals. CONCLUSIONS: The results of this study suggest that adjunctive treatment with fluvoxamine increases the concentration of escitalopram. The QTc interval did not change in this condition.

Serum x03C9;-3 and x03C9;-6 Fatty Acids Are Not Associated with Personality Traits in Healthy Japanese Young People.

BACKGROUND: Recent studies have reported that polyunsaturated fatty acids (PUFAs) are associated with mood and behaviors including depression and suicide risk. The aim of this study was to examine the relationship between PUFAs and personality traits in healthy subjects. METHODS: A total of 279 subjects completed the Temperament and Character Inventory and Beck Depression Inventory. Serum levels of the PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), the x03C9;-6 fatty acid arachidonic acid (AA), and dihomo-x03B3;-linolenic acid were measured. RESULTS: Pearson's correlation analysis showed a positive correlation between DHA and cooperativeness scores. In the multiple regression analysis, harm avoidance scores were positively associated with AA, and a negative association was found between the EPA/AA ratio and reward dependence scores. However, these associations were nonsignificant after a Bonferroni correction. CONCLUSION: The results of the present study suggest that the blood levels of PUFAs are not likely to be associated with personality traits.

Therapeutic reference range for plasma concentrations of paroxetine in patients with major depressive disorders.

BACKGROUND: We investigated the relationship between plasma concentrations of paroxetine and the therapeutic effect of the drug, and we evaluated the therapeutic reference range for plasma concentration of paroxetine in patients with major depressive disorders (MDD). METHODS: In this study, 120 patients with MDD were treated with 10-40 mg/d of paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate the patients at 0, 1, 2, 4, and 6 weeks. At the 6-week treatment time point, the patients were divided into 7 groups according to their paroxetine plasma concentrations in increments of 20 ng/mL. We used an analysis of variance and a χ test to define the therapeutic reference range for plasma paroxetine concentrations. RESULTS: We used 50% as the cutoff values for the percentage of MADRS improvement to determine the responder rates, and we defined remitters as patients with MADRS scores <10 at the 6-week treatment time point. We analyzed the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL, and 60 ng/mL using the χ test. According to the results of the χ test in the responder rates, the 20-60 ng/mL plasma paroxetine group showed the highest effect size. CONCLUSIONS: The results of this study suggested that a range of 20-60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.

Preanalysis storage conditions influence the measurement of brain-derived neurotrophic factor levels in peripheral blood.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a pivotal role in regulating neuronal function throughout life, and this factor is regarded as a potential biomarker of mental disorders. However, previous studies have suggested that plasma BDNF levels are more variable than serum BDNF levels. METHODS: We determined the influence of time and temperature on the measurement of peripheral blood BDNF levels. Blood samples were aliquoted into four types of tubes, including tubes containing heparin, ethylenediaminetetraacetic acid (EDTA), and citrate for plasma, and anticoagulant-free tubes for serum. The samples were stored at 4 or 25°C for 0, 1, 2, 4, 6, 24 or 48 h, and the plasma and serum BDNF levels were measured using enzyme-linked immunosorbent assay. RESULTS: There were interindividual and interanticoagulant compound variability in the plasma BDNF levels. The measured plasma BDNF levels increased over time, whereas the serum BDNF levels remained unchanged. Furthermore, the BDNF levels detected in plasma stored in heparin tubes at 4°C and those for samples stored in EDTA tubes at 25°C were much higher than those of the other samples. CONCLUSION: This study indicates that measurements of plasma BDNF levels are dependent not only on the anticoagulant compounds but also on the storage time and temperature conditions used after blood sampling.

Relationships between vascular endothelial growth factor levels and temperament and character inventory traits in healthy Japanese subjects.

BACKGROUND AND AIM: Personality traits and vascular endothelial growth factor (VEGF) levels are both independently correlated with major depressive disorder and depressive mood. However, no studies have reported associations between personality traits and VEGF levels. Thus, we hypothesized that there is a correlation between the results of the Temperament and Character Inventory (TCI) and VEGF levels. METHODS: We investigated 179 healthy participants who completed the TCI. We collected a serum sample from each subject and measured each participant's VEGF level by an enzyme-linked immunosorbent assay (ELISA). Simple and multiple regression analyses were performed to examine the correlations between the scores on the seven TCI dimensions and several other factors, including gender, age and VEGF level. RESULTS: A total of 150 subjects completed the examination. Among the dimensions of the TCI, the harm avoidance (HA) scores were negatively correlated with VEGF levels, but there were no significant correlations between the scores for any other dimensions and VEGF levels. The HA score was significantly correlated with sex, age and VEGF level, and single and multiple regression analyses yielded the same results. CONCLUSION: VEGF may be associated with certain personality factors. This study is the first to demonstrate a direct association between VEGF levels and a dimension of the TCI in healthy subjects.

Interaction between paliperidone and carbamazepine.

BACKGROUND: This aim of this study was to determine the impact of carbamazepine on the pharmacokinetics of paliperidone. METHODS: Six schizophrenic patients initially received a 6-12 mg/d dose of paliperidone alone. Subsequently, a 200 mg/d dose of carbamazepine was administered, and the carbamazepine dose was increased to 400 mg/d and then 600 mg/d. Plasma concentrations of paliperidone before and after carbamazepine coadministration were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Carbamazepine significantly reduced the plasma concentration of paliperidone. The plasma concentration of paliperidone at baseline and with coadministration of 200, 400, and 600 mg/d were 45.8 ± 11.7, 26.9 ± 13.7, 17.1 ± 8.2, and 15.9 ± 7.6 ng/mL, respectively. The concentration of paliperidone with carbamazepine coadministration at doses of 200, 400, and 600 mg/d were 55.7% ± 20.7%, 36.1% ± 12.2%, and 33.6% ± 10.4%, respectively, of baseline. This effect occurred even at the carbamazepine dose of 200 mg/d and reached a plateau at doses higher than 400 mg/d. However, carbamazepine coadministration exacerbated the psychotic symptoms in some patients. CONCLUSIONS: The results of the present study suggest that adjunctive treatment with carbamazepine reduces the concentration of paliperidone in a dose-dependent manner, most likely because of the induction of several drug-metabolizing enzymes and several drug transporters.

The CLOCK C3111T polymorphism is associated with reward dependence in healthy Japanese subjects.

BACKGROUND: The Circadian Locomotor Output Cycles Kaput (CLOCK) T3111C polymorphism has been associated with several psychiatric disorders, including mood disorders and schizophrenia, which are linked to specific personality traits. We investigated the relationship between the personality traits measured by the Temperament and Character Inventory (TCI) and the C3111T polymorphism of the CLOCK gene in healthy Japanese subjects. METHODS: The sample population contained 1,092 healthy subjects (age = 27.4 ± 8.7 years) who completed the TCI. Genomic DNA was isolated from whole blood and genotyped using the TaqMan allele-specific assay method. The associations between the gene polymorphisms and TCI scores were evaluated by one-way analysis of variance and multiple regression analysis. We also compared the TCI scores between the C allele carrier (C/T and C/C genotypes) and non-carrier (T/T genotype) groups using Student's t test. Males and females were analyzed separately. RESULTS: There was no significant association between the C3111T genotype and any TCI score, but multiple regression analyses revealed significant but opposite associations between reward dependence and the C3111T polymorphism in males and females (p = 0.032, ß = 0.087 and p = 0.05, ß = -0.087, respectively). Similarly, when we compared the TCI scores of CLOCK C3111T C carrier and non-carrier subjects, we found that male C allele carriers had significantly higher reward dependence scores than non-carriers (p = 0.02). CONCLUSION: Our findings suggest that the CLOCK C3111T polymorphism may affect personality traits in healthy Japanese subjects.

No association between a polymorphism in the serotonin receptor 2B (HTR2B) gene and personality traits in healthy Japanese subjects.

AIM: The brain neurotransmitter serotonin affects many aspects of human behavior, including personality traits. Because the serotonin receptor 2B (HTR2B) gene has recently been associated with impulsivity, we investigated the potential association between the rs10194776 and Q20* polymorphism in the HTR2B gene and personality traits in healthy subjects. METHODS: A total of 1,171 healthy Japanese subjects were enrolled in this study. Their personality traits were evaluated using the Temperament and Character Inventory (TCI), and the rs10194776 and Q20* genotype was determined using real-time polymerase chain reaction. RESULTS: There was a significant main effect of the rs10194776 polymorphism on harm avoidance and self-directedness in females (p = 0.037 and p = 0.043, respectively). However, these differences were insignificant after a Bonferroni correction. Subjects carrying the minor allele of the Q20* polymorphism were nonexistent. CONCLUSION: The results of the present study suggest that the HTR2B polymorphism is not likely to be associated with personality traits, including novelty seeking and impulsivity.

No association between hormonal abnormality and sexual dysfunction in Japanese schizophrenia patients treated with antipsychotics.

OBJECTIVE: Although sexual dysfunction is believed to be caused by hormonal abnormalities, few reports have studied sexual dysfunction and its association with hormonal abnormalities in Asian populations with schizophrenia. METHODS: We employed a cross-sectional, case-control survey design to collect data from 191 (108 men) Japanese schizophrenia outpatients treated with antipsychotics and 182 (49 men) healthy subjects. Sexual dysfunction was evaluated using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. We measured plasma concentrations of prolactin in both genders and testosterone in men and estradiol in women. RESULTS: Multiple regression analyses revealed the following findings: the number of antipsychotics correlated with diminished sexual desire (standardized beta = 0.241, p < 0.05); the dose of antipsychotics correlated with gynecomastia (standardized beta = 0.277, p < 0.01), increased sexual desire (standardized beta = 0.229, p < 0.05), and ejaculatory dysfunction (standardized beta = 0.248, p < 0.05); and the dose of antipsychotics correlated with menorrhagia in women (standardized beta = 0.284, p < 0.05). However, neither plasma concentrations of prolactin, testosterone nor estradiol correlated with sexual dysfunction. CONCLUSIONS: The present study demonstrated that an association between sex hormone abnormalities and sexual dysfunction is unlikely but that the dose or number of antipsychotics is associated with some sexual dysfunction.

Factor structure of the Liebowitz Social Anxiety Scale in community-dwelling subjects in Japan.

This study examined the internal consistency and structural/construct validity of the Liebowitz Social Anxiety Scale (LSAS) for community-dwelling subjects in Japan. A cross-sectional study that included 929 participants was conducted. Structural/construct validity was assessed on confirmatory factor analysis. The internal consistency reliability was good for the overall LSAS scale (α = 0.97) and for its original four factors (α = 0.92-0.89). The original four-factor model fit the observed data relatively better than alternative models. These findings indicate that the LSAS is a valid and reliable measure of anxiety symptoms for this community-dwelling population in Japan.

Body composition in patients with schizophrenia: Comparison with healthy controls.

BACKGROUND: Recently, a relationship between obesity and schizophrenia has been reported. Although fat- mass and fat free mass have been shown to be more predictive of health risk than body mass index, there are limited findings about body composition among patients suffering from schizophrenia. The aim of this study is to compare the body composition of schizophrenia patients with that of healthy subjects in Japan. METHODS: We recruited patients (n = 204), aged 41.3 ± 13.8 (mean ± SD) years old with the DSM-IV diagnosis of schizophrenia who were admitted to psychiatric hospital using a cross-sectional design. Subjects' anthropometric measurements including weight, height, body mass index (BMI), and medications were also collected. Body fat, percent (%) body fat, fat- free mass, muscle mass, and body water were measured using the bioelectrical impedance analysis (BIA) method. Comparative analysis was performed with schizophrenic subjects and 204 healthy control individuals. RESULTS: In a multiple regression model with age, body mass index, and dose in chlorpromazine equivalents, schizophrenia was a significantly linked with more body fat, higher % body fat, lower fat- free mass, lower muscle mass, and lower body water among males. In females, schizophrenia had a significant association with lower % body fat, higher fat- free mass, higher muscle mass, and higher body water. CONCLUSIONS: Our data demonstrate gender differences with regard to changes in body composition in association with schizophrenia. These results indicate that intervention programs designed to fight obesity among schizophrenic patients should be individualized according to gender.

No association between dietary patterns and depressive symptoms among a community-dwelling population in Japan.

BACKGROUND: Studies of the associations between diet and depression have primarily focused on single nutrients or foods. Recently, dietary patterns representing a combination of foods have attracted more interest than individual nutrient. The objective of this study was to examine the association between dietary patterns and depressive symptoms among a community-dwelling population in Japan. METHODS: We examined the association between dietary patterns and the risk of depression among 791 Japanese community-dwelling individuals. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups [energy-adjusted food (g/d)] were extracted by principal component analysis. The Center for Epidemiologic Studies Depression Scale (CES-D) with a cut-off point of 16 was used to assess the prevalence of depression. RESULTS: A total of 97 subjects (12.3%) were classified as having depression. Four dietary patterns were identified: "Healthy", "Western", "Bread and confectionery", and "Alcohol and accompanying" dietary patterns. After adjusting for potential confounders, the dietary patterns were not related to the risk of depression. CONCLUSIONS: The present study failed to find associations between dietary patterns and the risk of depression. However, the interpretation of our results was hampered by the lack of certain data, including employment physical activity and longitudinal observations. Potential associations between dietary patterns and depressive symptoms were not completely ruled out. Future research exploring dietary patterns and depressive symptoms is warranted.

Effect of age and disease on bone mass in Japanese patients with schizophrenia.

BACKGROUND: There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. METHODS: We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI) was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. RESULTS: Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. CONCLUSIONS: Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.