Association Between Serum Insulin-Like Growth Factor 1 Levels and the Clinical Symptoms of Chronic Schizophrenia: Preliminary Findings.

Purpose: Insulin-like growth factor 1 (IGF-1) is a trophic mediator that is regulated by growth hormone and associated with the proliferation, development, and growth of neural cells. IGF-1 may be associated with the pathophysiology of schizophrenia, but this association remains controversial. This study aimed to investigate the relationship between serum IGF-1 levels and psychiatric symptoms in patients with chronic schizophrenia. Patients and Methods: A total of 65 patients were recruited from the University of Occupational and Environmental Health, Komine Eto Hospital, Moji Matsugae Hospital, Shin-Moji Hospital, and Tsutsumi Hospital in Kitakyushu between September 2019 and June 2020. Further, 20 healthy age- and sex-matched control participants were recruited from the Komine Eto Hospital and the University of Occupational and Environmental Health. Patients with schizophrenia were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Drug-Induced Extrapyramidal Symptoms Scale. Serum levels of free plus albumin-bound IGF-1 (IGF-1) were measured by immunoradiometric assay. The measurements were performed using antibody beads for bound/free separation. Associations between serum IGF-1 levels and the PANSS scores were determined. We also examined the associations between serum IGF-1 levels and diabetes, antipsychotic drug use, and disease duration. Results: No significant difference was found in the serum IGF-1 level between patients with schizophrenia and healthy controls. Serum IGF-1 levels were significantly negatively correlated with the PANSS total score (R 2 = 0.06, p = 0.015) and PANSS general score (R 2 = 0.088, p = 0.008), but not with the PANSS positive scores and PANSS negative scores. Serum IGF-1 levels were not related to the prevalence of diabetes (p = 0.64). However, a significant correlation was observed between serum IGF-1 levels and age (B = -1.88, p < 0.0001). Serum IGF-1 levels could not distinguish patients with schizophrenia and healthy controls. Conclusion: The association between serum IGF-1 levels and psychiatric symptoms may be complicated in patients with chronic schizophrenia.

The Impact of Aging, Psychotic Symptoms, Medication, and Brain-Derived Neurotrophic Factor on Cognitive Impairment in Japanese Chronic Schizophrenia Patients.

Background: Cognitive impairment in schizophrenia can result in considerable difficulty in performing functions of daily life or social rehabilitation. Cognitive impairment in schizophrenia is related to various factors, such as the psychotic severity, aging, medication, and brain-derived neurotrophic factor (BDNF). To date, however, no studies investigating the impact of these factors on cognitive functioning in chronic schizophrenia patients have been performed. Objective: The aim of this study is to identify those factors that influence the cognitive functioning in patients with chronic schizophrenia. Methods: Sixty-five of 116 long-term hospitalized chronic schizophrenia patients (63.8 ± 12.1 years old, M/F = 29/36) were enrolled this cross-sectional study. We investigated the relationship among the patients' age, psychotic severity, treatment medication, serum BDNF levels, and cognitive functioning (measured by the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia; BACS-J). Additionally, we performed a multivariable linear regression analysis. Results: According to the partial correlation analysis, certain parameters [i.e., age, chlorpromazine (CP) equivalent, biperiden (BP) equivalent, and serum BDNF] were significantly correlated with cognitive functioning, including working memory (WM), motor function (MF), attention and processing speed (AP), and executive function (EF). For the multivariate analysis, the MF component, which had the highest correlation, was selected as the dependent variable, and the independent variables included age, Manchester Scale for chronic psychosis (ManS) total score, CP equivalent, BP equivalent, serum BDNF, estimated full scale IQ, and years of education. According to the multiple regression analysis of this model, R (multiple regression coefficient) was 0.542, the adjusted R2 (coefficient of determination) was 0.201, and only BP equivalent (ß = -0.305, p = 0.030), but not age, ManS score, CP equivalent, or serum BDNF, could significantly explain MF at the 5% significant level. Conclusion: In conclusion, aging, medication (administering more antipsychotics or anticholinergics), and serum BDNF concentration are significantly correlated with cognitive dysfunction in chronic schizophrenia patients but not with the severity of psychotic symptoms. Furthermore, only the anticholinergic dosage had a significant causal relationship with MF. Thus, the use of anticholinergics in chronic schizophrenia patients with deteriorating cognitive functioning must be reconsidered.

The Nursing Assessment of Medication Acceptance: the reliability and validity of a schizophrenia medication adherence scale.

BACKGROUND: Many patients with schizophrenia have low medication adherence. There is, however, no objective assessment scale that can be used by nurses or caregiver specialists. The Nursing Assessment of Medication Acceptance (NAMA) was developed to assess patients' medication adherence. The aim of this study was to examine the validity and reliability of the NAMA in patients with schizophrenia. METHODS: A total of 121 Japanese patients with schizophrenia were enrolled. All patients underwent evaluation using the NAMA and the Drug Attitude Inventory (DAI-10). Reliability was investigated using a test-retest method and a parallel-test method. To determine the test-retest reliability of the NAMA, we tested 101 schizophrenia patients twice, with the second assessment 2-4 weeks after the date of the first assessment. For validity verification, standard-related validity and the degree of concordance with the DAI-10 scores were measured. RESULTS: The Cronbach's alpha value of the NAMA in schizophrenia was 0.88. The test-retest correlation coefficients were all between 0.53-0.74. The total scores and all subscores for the NAMA were significantly correlated, and the NAMA total scores were significantly correlated with the DAI-10 total scores. CONCLUSIONS: The NAMA shows good reliability and validity in measuring medication adherence in schizophrenia.

Comparison of N-acetyltransferase-2 enzyme genotype-phenotype and xanthine oxidase enzyme activity between Swedes and Koreans.

The aim of this study was to compare xanthine oxidase (XO) and N-acetyltransferase-2 (NAT2) genotype and phenotype between Swedes (n = 113) and Koreans (n = 150), as well as to investigate the effect of sex, smoking, age, and oral contraceptive (OC) use on enzyme activities, using caffeine as a probe. XO and NAT2 activities were estimated by 1U/(1U+1X) and AFMU/(AFMU+1X+1U) urinary ratios, respectively. Participants were genotyped for 191G>A, 341T>C, 590G>A, and 857G>A NAT2 polymorphisms. There was no significant difference in XO activity between Swedes and Koreans. In Swedes, higher XO activity was observed in women (P < .003). There were significant differences in NAT2 genotype and phenotype between Swedes and Koreans. Koreans display significantly higher frequency of NAT2 fast acetylator genotype (89%), whereas the slow acetylator genotype is predominant (62%) in Swedes (P < .0001). Significantly higher NAT2 activity was observed in Koreans compared to Swedes (P < .0001). Having the same NAT2 fast acetylator genotype, Koreans display higher enzyme activity than Swedes (P < .004). OC use significantly increased NAT2 activity in Swedish women. In conclusion, Koreans display higher NAT2 activity than Swedes regardless of NAT2 genotype. Ethnicity, OC use, and genotype determine NAT2 activity, whereas sex is the only determinant of XO activity.

Reliability, validity and clinical utility of a Japanese version of the Social Adaptation Self-evaluation Scale as calibrated using the Beck Depression Inventory.

AIM: The Social Adaptation Self-evaluation Scale (SASS) was developed to assess the social impairment caused by depression. The purposes of this study were to develop a Japanese version of the SASS (SASS-J) and to evaluate its reliability and validity. METHODS: The SASS-J and the 21-item Beck Depression Inventory (BDI) were administered to 322 participants (95 working patients who were working while under treatment for depression, 99 non-working patients who were absent from their work due to depression, and 128 healthy controls). The healthy controls underwent both questionnaires twice, at baseline and 2 weeks later, in order to assess test-retest reliability. RESULTS: Cronbach's alpha was 0.81. Significance correlations were found between SASS-J scores at baseline and 2 weeks later in healthy controls (R = 0.845, P < 0.001). There were negative correlations between the SASS-J and BDI scores (ρ = -0.683, P < 0.001). Mean SASS-J scores differed significantly among the three groups (working patients: 33.7 ± 7.9; non-working patients: 25.2 ± 7.8; healthy controls: 36.1 ± 6.0 [mean ± SD]). The best compromise between the true positive and the false negative rate in this study was at a cut-off point of 25/26. CONCLUSION: SASS-J showed sufficient reliability and validity, and could be considered a suitable instrument to evaluate social functioning in depressive patients.

Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients.

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI.

Three polymorphisms of the eNOS gene and plasma levels of metabolites of nitric oxide in depressed Japanese patients: a preliminary report.

BACKGROUND: Depression is a risk factor for coronary heart disease. Nitric oxide (NO) plays an important role in both coronary heart disease and depression. METHODS: Fifty-one inpatients and outpatients who met the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition criteria for major depressive disorder (MDD) in the university hospital of the University of Occupational and Environmental Health and 58 age-matched and sex-matched healthy controls enrolled in this study. We investigated the association between the three polymorphisms of the endothelial nitric oxide synthase (eNOS) gene (single-nucleotide polymorphism (SNP); rs2070744, rs1799983, variable number tandem repeat (VNTR) in intron 4) and scores on the Hamilton Rating Scale for Depression, plasma metabolites of NO (NO(x) ) or ankle brachial index in patients with MDD and healthy controls. RESULTS: We did not find significant differences in the genotype distributions between patients with MDD and healthy volunteers. No associations were observed between any of the polymorphisms of the eNOS gene and the Hamilton Rating Scale for Depression or ankle brachial index in patients with MDD. However, plasma NO(x) level was significantly associated with a polymorphism of the eNOS gene (rs207044 and variable number tandem repeat in intron 4). CONCLUSION: These results suggest that the direct association was not observed between the polymorphisms of the eNOS gene and the pathogenesis of depression.

Long-term effect of efavirenz autoinduction on plasma/peripheral blood mononuclear cell drug exposure and CD4 count is influenced by UGT2B7 and CYP2B6 genotypes among HIV patients.

OBJECTIVES: We investigated the long-term effect of efavirenz autoinduction on its plasma/peripheral blood mononuclear cell (PBMC) exposure and the CD4 count, and the importance of sex and pharmacogenetic variations. METHODS: Treatment-naive HIV patients (n = 163) received efavirenz-based antiretroviral therapy. Plasma and intracellular (PBMC) concentrations of efavirenz and 8-hydroxyefavirenz were determined at weeks 4 and 16 of antiretroviral therapy. CD4 count was determined at baseline, and at weeks 12, 24 and 48. Genotyping for CYP2B6*6, CYP3A5*3, CYP3A5*6, CYP3A5*7, ABCB1 3435C/T and UGT2B7 (-327G→A, *2) was done. RESULTS: There was a significant increase in the median plasma (32%) and intracellular (53%) 8-hydroxyefavirenz concentrations with a decrease in the efavirenz metabolic ratio (MR) (calculated by dividing the concentration of efavirenz by that of 8-hydroxyefavirenz) (20% and 5%, respectively) by week 16 compared with at week 4. While the CYP2B6 genotype significantly influenced efavirenz pharmacokinetics at weeks 4 and 16, the effect of the UGT2B7 genotype and sex was significant only at week 16. The Wilcoxon matched pairs test indicated that the change in 8-hydroxyefavirenz concentration and efavirenz MR over time was significant in females and in CYP2B6*1 and UGT2B7*1 carriers. The intracellular 8-hydroxyefavirenz level at week 16 was a negative predictor of the CD4 count at week 24 (P = 0.03) and at week 48 (P = 0.007). CYP2B6 (P = 0.02) and UGT2B7 (P = 0.05) genotypes predicted the CD4 count at week 48. Among CYP2B6*1/*1 and UGT2B7*1/*1 carriers there was no significant change in the mean CD4 count after week 24, while it continuously increased until week 48 in CYP2B6*6 and UGT2B7*2 carriers. CONCLUSIONS: The effects of long-term efavirenz autoinduction on its plasma/PBMC exposure and the CD4 count over time display wide interpatient variability, partly due to sex and CYP2B6 and UGT2B7 genetic variation. Patients with the CYP2B6*1/*1 and UGT2B7*1/*1 genotypes are at risk of suboptimal immune recovery due to pronounced long-term autoinduction.

N-Acetyltransferase-2 (NAT2) gene polymorphisms and enzyme activity in Serbs: unprecedented high prevalence of rapid acetylators in a White population.

The aim of this study was to investigate N-acetyltransferase 2 (NAT2) genetic polymorphism and enzyme activity in Serbs, and to examine the influence of NAT2 genotype, sex, and smoking on the phenotype. Genotyping for 190C>T, 282C>T, 341T>C, 403C>G, 411T>A, 481C>T, 590G>A, 803A>G, and 857G>A in the NAT2 gene, was performed in 140 healthy Serbs. NAT2 activity was determined as AFMU/ (AFMU + 1X + 1U) urinary ratio in 100 subjects using caffeine as a probe. The most frequent NAT2 haplotypes were NAT2*5B (38.2%), NAT2*6A (26.0%), and NAT2*4 (24.4%). The log-transformed NAT2 activity indices exhibited trimodal distribution with 9%, 36%, and 55% of slow, intermediate, and rapid acetylators, respectively. Significant NAT2 genotype-phenotype correlation was observed (P < .0001). The frequency of NAT1*10 and NAT1*11 were 27.5% and 6.9%, respectively. There was no significant influence of sex or cigarette smoking on NAT2 enzyme activity. Eight subjects displayed rapid NAT2 acetylators phenotype despite being homozygous for NAT2 slow alleles, and NAT1 fast acetylators genotype (NAT1*10 and NAT1*11) had no implication. In contrast to other white populations described hitherto, rapid acetylator is the predominant NAT2 phenotype in Serbs. NAT2 genotype, but not sex and cigarette smoking, influence enzyme activity. NAT1 fast acetylators genotypes do not contribute for NAT2 genotype-phenotype discordance.

Relationships between stress, social adaptation, personality traits, brain-derived neurotrophic factor and 3-methoxy-4-hydroxyphenylglycol plasma concentrations in employees at a publishing company in Japan.

There is growing evidence that blood levels of brain-derived neurotrophic factor (BDNF) and 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of noradrenaline, are related to depression-associated personality traits as well as to depressive, suicidal and anxious states. Psychological job stress is well known to lead to symptoms of depression, anxiety and suicide. We have recently reported that psychological job stress among hospital employees altered blood levels of BDNF and MHPG (Mitoma et al., 2008). In the present study, we re-examined the effects of social adaptation and personality traits, as well as those of psychological job stress, on plasma levels of BDNF and MHPG in healthy employees (n=269, male/female=210/59, age=49 ± 10years) working in a publishing company in Japan. The values (mean ± SD) of scores on the Stress and Arousal Check Lists (s-SACL and a-SACL), Social Adaptation Self-evaluation Scale (SASS), plasma MHPG levels and plasma BDNF levels were 6.0 ± 3.4, 5.7 ± 2.3, 33.7 ± 6.8, 5.8 ± 4.3 and 4.6 ± 3.1ngml(-1), respectively. A positive correlation was found between plasma MHPG levels and scores on the s-SACL, but not the a-SACL. A positive correlation was also found between SASS scores and plasma MHPG levels and between SASS scores and plasma BDNF levels. A negative correlation was found between plasma BDNF levels and s-SACL scores. Furthermore, a positive correlation between NEO-Five factor Inventory (Openness) scores and plasma MHPG levels was observed, as well as between NEO-Five factor Inventory (Extroversion) scores and plasma BDNF levels. These results suggest that levels of plasma BDNF and plasma MHPG might be associated with psychological job stress and certain personality traits among employees in the publishing industry in Japan.

[Blood levels of brain-derived neurotrophic factor (BDNF) in major depressive disorder].

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been linked to the viability of neurons in brain circuits that regulate emotion, memory, learning, sleep, and appetite. BDNF has been most extensively studied in relation to depression. Depressed patients show reduced levels of hippocampal and cortical BDNF in postmortem studies. Recently, to the best of our knowledge, there are at least three meta-analyses regarding blood BDNF levels in depressed patients, suggesting that blood BDNF levels are decreased in depressive state, and those are recovered after treatment with biological treatments such as antidepressants, ECT, and rTMS. From these findings into account, it is possible that blood (plasma and serum) BDNF level is a biological marker for depressive state. We have recently demonstrated that a significantly negative correlation was observed between the HAMD scores and serum BDNF levels. In addition, responders to fluvoxamine, paroxetine, milnacipran, and sertraline all increased serum BDNF levels. Blood BDNF levels did not distinguish between responders and remitters to the treatment. In conclusion, blood BDNF levels partially reflect those in the brain, and there is also strong and consistent evidence indicating that these levels normalize following the biological intervention for depression.

No difference in adherence to paroxetine between depressed patients with early remission and those with late remission based on monitoring of plasma paroxetine concentrations.

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat both anxiety disorders and depressive disorders. However, nonadherence to SSRIs is a major issue in recurrence. In the present study, we investigated paroxetine adherence in depressed patients by monitoring the plasma paroxetine concentrations between patients with rapid and those with a late response to paroxetine treatment. Twenty inpatients in our university hospital, who met the DSM-IV-TR diagnosis of major depressive disorder in a single episode, were enrolled in the study. Twelve patients (M/F: 7/13, age: 37.4 +/- 10.4 years) were treated with paroxetine (40 mg/day), and all achieved remission (HAMD < or = 7) within at least 12 weeks. We divided the patients into two groups, an early-remission group (HAMD < or = 7 within 4 weeks) and a late-remission group (HAMD < or = 7 within 8-12 weeks). Their dosages of paroxetine were constant because of no emerging adverse effects. Blood samples were obtained on the day the subjects were discharged (B) and 12 weeks after discharge. The paroxetine concentrations in the early-remission group were significantly decreased 12 weeks after discharge, and no difference was found between the early- and late-remission groups. These results suggest that adherence to paroxetine was independent of the duration of the depressive state suffered by the patients. Clinicians always take their cautions for the adherence to paroxetine regardless of the clinical time courses the patients recovering from their depressive symptoms.

Critical examination of a correlation between brain gamma-aminobutyric acid (GABA) concentrations and a personality trait of extroversion in healthy volunteers as measured by a 3 Tesla proton magnetic resonance spectroscopy study.

We hypothesized that brain gamma-aminobutyric acid (GABA) levels are associated with neuroticism, a trait associated with depression and anxiety disorders. We examined the correlation between brain GABA concentrations and the five factors included in the NEO Five-Factor Inventory (NEO-FFI) in healthy volunteers using magnetic resonance spectroscopy (MRS) at 3 T. Forty-one healthy subjects (21 males, 20 females; age: 35+/-7 years) were enrolled in this study. Each subject underwent a 3T 1H-MRS study with a MEGA-PRESS sequence. Spectroscopy voxels (3 cm x 3 cm x 3 cm) were placed in the frontal lobe and the parieto-occipital lobe. A negative correlation was found between the GABA/creatine ratios in the frontal lobe and scores of extroversion on the NEO-FFI. These results suggest that GABAergic neurons are related to personality traits of healthy subjects.

Different patterns of longitudinal changes in plasma levels of catecholamine metabolites and brain-derived neurotrophic factor after administration of atypical antipsychotics in first episode untreated schizophrenic patients.

In the present study, we longitudinally investigated the effects of risperidone, olanzapine, and aripiprazole on plasma levels of catecholamine metabolites and brain-derived neurotrophic factor (BDNF) in first-episode unmedicated schizophrenic patients. The subjects were 59 Japanese schizophrenic patients (35 males and 24 females; age range: 18-46 years; mean+/-SD: 25+/-16 years). The patients were treated with risperidone (n=32) in a dose range of 2-6 mg/day (mean+/-SD=3.4+/-1.9), olanzapine (n=18) in a dose range of 5-20 mg/day (mean+/-SD=12.1+/-5.8), or aripiprazole (n=9) in a dose range of 12-30 mg/day (mean+/-SD=22.8+/-10.1). All three drugs significantly decreased plasma homovanillic acid (HVA) levels within 8 weeks, although aripiprazole transiently raised this level before 8 weeks. All three drugs also significantly increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels within 8 weeks. On the other hand, none of them altered plasma BDNF levels. These results indicate that risperidone, olanzapine, and aripiprazole affect catecholaminergic systems in the brain, that the effects of aripiprazole on the dopaminergic systems seem to slightly different than those of risperidone and olanzapine, and that these atypical antipsychotic drugs might not alter BDNF levels, at least within 8 weeks of treatment.

Pathophysiological analysis of female Spontaneously Diabetic Torii fatty rats.

Obesity, hyperglycemia, hyperlipidemia, and diabetes-associated complications appear at younger ages (6-8 weeks) in the male Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat than in the male original SDT (SDT-+/+) rat. However, the incidence and progression of diabetes mellitus and diabetic complications in the female SDT-fa/fa rat have not been reported in detail. In the present study, the pathophysiological features of the female SDT-fa/fa rat were examined, and compared with those of the female SDT-+/+ rat. Female SDT-fa/fa rats showed hyperphagia, obesity, hyperglycemia, and hyperlipidemia from 5 or 6 weeks of age, and hyperinsulinemia was observed from 5 to 12 weeks. Pathological changes pancreatic islets were observed from 8 weeks. Renal function parameters, such as urine volume and urinary protein, increased from 16 weeks, and pathological findings in the renal tubule, and cataracts were also observed from 16 weeks. Increases of visceral and subcutaneous fats were obvious during the observation period. In pair-feeding with SDT-+/+ rats, SDT-fa/fa rats showed improved hyperglycemia and hypertriglycemia, but hypercholesterolemia was not entirely improved during the study period. Female SDT-fa/fa rats showed diabetes mellitus and diabetes-associated complications at young ages, and fat accumulation was remarkable. Suppression of hyperphagia in SDT-fa/fa rats was effective at improving hyperglycemia and hypertriglycemia. In conclusion, the female SDT-fa/fa rat has the potential to become an important animal model of type 2 diabetes mellitus with obesity, especially for women, for which few models currently exist.

Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study.

Nitric oxide (NO) is involved in pathophysiology of psychiatric disorders such as depression and schizophrenia. We hypothesize that plasma levels of NO and its metabolites (NO(x)) are decreased in patients with schizophrenia. To examine the hypothesis, we compared plasma NO(x) levels between 30 schizophrenic patients (M/F: 18/12, age: 38 +/- 15 years) and age- and sex-matched 30 healthy controls (M/F: 18/12, age: 41 +/- 19 years), and we also examined the effects of risperidone on plasma NO(x) levels in schizophrenic patients. The baseline plasma NO(x) levels were significantly lower in the schizophrenia group (1.85 +/- 0.70 microM) than those in control group (3.37 +/- 2.27 microM). A significantly negative correlation was found between plasma NO(x) levels and PANSS-N scores before risperidone administration (rho = -0.385, p = 0.0416). Treatment with risperidone significantly increased the plasma NO(x) levels by 8 weeks (before; 1.85 +/- 0.70 microM, after; 2.25 +/- 1.00 microM, p = 0.0491). These results suggest that NO might be one of the candidates factors which are associated with the pathophysiology of negative symptoms of schizophrenia.

Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious but potentially treatable disease. However, biological markers such as IgG index or IL-6 do not always reflect the severity of the psychotic symptoms of NPSLE. We hypothesized that serum BDNF levels may be a biological marker for reflecting the severity of the psychiatric symptoms of NPSLE. METHODS: The participants enrolled in this study were 28 healthy volunteers and 54 Japanese SLE inpatients at the University Hospital of Occupational and Environmental Health, all of whom fulfilled the criteria for the classification of SLE. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms including an acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis (NP group); NPSLE without psychiatric symptoms (NN group); and SLE without neuropsychiatric symptoms (S group). The serum BDNF levels were measured by ELISA. RESULTS: Serum BDNF levels were significantly increased in the NP group (mean +/- SE = 37.0 +/- 5.46 ng/ml) compared with those in the other three groups (NN group; mean +/- SE = 9.1 +/- 2.44 ng/ml, P < 0.0001, S group; mean +/- SE = 10.4 +/- 2.51 ng/ml, P < 0.0001, healthy control; mean +/- SE = 11.44 +/- 0.69, P < 0.0001). Subsequently, serum BDNF levels were decreased in parallel with the improvement of psychiatric symptoms in the NP group. CONCLUSION: These results suggest that serum BDNF is a biological marker for the severity of psychiatric symptoms in NPSLE patients.

A close correlation between plasma and serum levels of brain-derived neurotrophic factor (BDNF) in healthy volunteers.

Abstract Objective. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic family found in both the central and the peripheral nervous system. Blood BDNF levels are considered as a state marker for depression. Methods. We investigated serum and plasma levels of BDNF levels in 103 healthy volunteers (M/F: 39/64, age: 37±12 years) using ELISA methods. Results and Conclusions. Serum BDNF levels were 14-fold higher than plasma BDNF levels, and a close relationship was found between serum and plasma BDNF levels.