Plasma fatty acid-binding protein 7 concentration correlates with depression/anxiety, cognition, and positive symptom in patients with schizophrenia.

Because of the involvement of the brain in the pathophysiology of psychiatric disorders, obtaining information on the biochemical features that directly contribute to symptoms is challenging. The present study aimed to assess fatty acid-binding protein 7 (FABP7) expressed specifically in the brain and detectable in the peripheral blood and to investigate the correlation between blood FABP7 concentration and symptoms. We recruited 30, 29, and 35 patients with schizophrenia, bipolar disorder, and depression and evaluated using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAMD-21), respectively. Plasma FABP7 concentrations correlated with PANSS scores (R2 = 0.3305, p < 0.001) but not with other scales. In the analysis of the relationship between five dimensions of schizophrenia symptoms derived from the PANSS 5-factor model and measured plasma FABP7 concentrations, severities of depression/anxiety, cognition, and positive symptom were significantly correlated with plasma FABP7 concentrations. Further molecular investigation of the functional and kinetic analyses of FABP7 is necessary to understand the relationship of this protein with schizophrenia pathology. Nevertheless, the present study suggests that FABP7 can be a biological indicator reflecting the pathogenesis of schizophrenia and has potential applications as a biomarker for diagnosis and symptom assessment.

Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine.

The dopamine and glutamate hypotheses reflect only some of the pathophysiological changes associated with schizophrenia. We have proposed a new "comprehensive progressive pathophysiology model" based on the "dopamine to glutamate hypothesis." Repeated administration of methamphetamine (METH) at a dose of 2.5 mg/kg in rats has been used to assess dynamic changes in the pathophysiology of schizophrenia. Previous use of this model suggested N-methyl-d-aspartate receptor (NMDA-R) dysfunction, but the mechanism could only be inferred from limited, indirect observations. In the present study, we used this model to investigate changes in the expression of NMDA-R subunits. Repeated administration of METH significantly decreased the gene expression levels of glutamate ionotropic receptor NMDA type subunit (Grin) subtypes Grin1 and Grin2c in the prefrontal cortex (PFC), Grin1 and Grin2a in the hippocampus (HPC), and Grin1, Grin2b, and Grin2d in the striatum (ST).We observed a significant difference in Grin1 expression between the PFC and ST. Furthermore, repeated administration of METH significantly decreased the protein expression of GluN1 in both cytosolic and synaptosomal fractions isolated from the PFC, and significantly decreased the protein expression of GluN1 in the cytosolic fraction, but not the synaptosomal fraction from the ST. These regional differences may be due to variations in the synthesis of GluN1 or intracellular trafficking events in each area of the brain. Considering that knockdown of Grin1 in mice affects vulnerability to develop schizophrenia, these results suggest that this model reflects some of the pathophysiological changes of schizophrenia, combining both the dopamine and glutamate hypotheses.

Pilot Validation Study of the Japanese Translation of the Brief Negative Symptoms Scale (BNSS).

PURPOSE: The brief negative symptoms scale (BNSS) is a concise instrument used to assess negative symptoms of subjects with schizophrenia covering five domains of negative symptoms and is suitable for use in clinical, experimental, and epidemiological settings. The original and translated version of BNSS has thus far been shown to have adequate psychometric properties. This study aimed to examine internal consistency, inter-rater and test-retest reliability, discriminant and convergent validity, and factor structure of the Japanese version of BNSS. PATIENTS AND METHODS: The assessment was performed by 11 raters using interview videos of nine subjects. Reliability was calculated with Cronbach's alpha for internal consistency and intra class correlation coefficient (ICC) for inter-rater reliability. Pearson's correlation coefficients were calculated to estimate the test-retest reliability. In addition to BNSS, Scale for assessment of negative symptoms (SANS) and scale for assessment of positive symptoms (SAPS) was obtained to assess the convergent and discriminant validity. Factor structure was assessed using principle factor analysis. RESULTS: The Japanese BNSS showed excellent internal consistency (Cronbach's alpha=0.95), inter-rater reliability (intra class correlation coefficient=0.97), and test-retest reliability (r=0.94, p<0.001). The convergent validity shown by correlation with SANS total score (r=0.87, p<0.001) and discriminant validity shown by correlation with SAPS total score (r=0.17, p=-0.68) were also good. Principal factor analysis revealed a two-factor structure of BNSS, although the loading of each item differed from that in the literature. CONCLUSION: Our pilot study demonstrated that Japanese BNSS had good psychometric properties which were achieved with relatively brief training. Further studies with more subjects and raters with various backgrounds recruited from multiple sites are warranted.

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study.

BACKGROUND: Studies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines. METHODS: In this open-label single-arm study, all participants received B. breve strain A-1 (1011 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition. RESULTS: Twenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders. LIMITATIONS: This open-label, single-arm study cannot exclude a placebo effect. CONCLUSIONS: The results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome.

The mediator effect of personality traits on the relationship between childhood abuse and depressive symptoms in schizophrenia.

Previous studies indicated that personality traits have a mediator effect on the relationship between childhood abuse and depressive symptoms in major depressive disorder and nonclinical general adult subjects. In the present study, we aimed to test the hypothesis that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. We used the following questionnaires to evaluate 255 outpatients with schizophrenia: the Child Abuse and Trauma Scale, temperament and character inventory, and Patients Health Questionnire-9. Univariate analysis, multiple regression analysis, and structured equation modeling (SEM) were used to analyze the data. The relationship between neglect and sexual abuse and the severity of depressive symptoms was mostly mediated by the personality traits of high harm avoidance, low self-directedness, and low cooperativeness. This finding was supported by the results of stepwise multiple regression analysis and the acceptable fit indices of SEM. Thus, our results suggest that personality traits mediate the relationship between childhood abuse and depressive symptoms in schizophrenia. The present study and our previous studies also suggest that this mediator effect could occur independent of the presence or type of mental disorder. Clinicians should routinely assess childhood abuse history, personality traits, and their effects in schizophrenia.

Hyperosmolar hyperglycemic state secondary to neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is often considered to be a precipitating factor for diabetic coma, such as a hyperosmolar hyperglycemic state (HHS). The combination of NMS and a systemic illness such as HHS can be difficult to diagnose because NMS may mask the coexisting condition. Although this coexistence is rare, it may be fatal if not detected early. We report a case of HHS in a 47-year-old male patient that developed after the distinguishing features of NMS had subsided. After the diagnosis of HHS, his recovery was a result of intravenous administration of soluble human insulin and fluid supplementation. Physicians caring for patients with diabetes who are also treated with neuroleptic agents should be aware that NMS may precipitate the development of secondary hyperglycemia despite a history of well-controlled blood glucose levels.