Kenji Sanada

Background: Previous meta‐analyses have reported lower serum adiponectin levels in patients with schizophrenia treated with second‐generation antipsychotics. However, the relationships among serum adipokines, psychiatric symptoms, and antipsychotic use remain unclear. This study aimed to clarify associations between serum adipokines, psychiatric symptoms, and antipsychotic treatment in patients with chronic schizophrenia compared with healthy controls. Methods: The study included 37 inpatients with schizophrenia and 39 age‐ and gender‐matched healthy controls. Fasting blood samples were collected, and serum adipokine levels were measured using enzyme‐linked immunosorbent assays. Psychiatric symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS), and antipsychotic doses were converted to chlorpromazine equivalents. Correlations were examined using regression and multivariate analyses, including adjustment for body mass index (BMI). Results: No significant case–control differences were observed in total or high‐molecular weight adiponectin levels. Female patients had a significantly higher leptin/adiponectin ratio than female controls ( p = 0.041). In the schizophrenia group, adiponectin levels were positively correlated with chlorpromazine equivalents ( r = 0.684, p < 0.001). This association remained statistically significant after adjustment for BMI, gender and hospitalization period. Adiponectin levels were not significantly associated with psychiatric symptom severity. Conclusion: In this cross‐sectional sample, serum adiponectin levels are associated with antipsychotic dosage but not with symptom severity. These findings suggest that adipokine regulation in patients with schizophrenia may be influenced by treatment‐related and demographic factors. Longitudinal studies incorporating comprehensive metabolic assessments are needed to explore the clinical significance of these relationships.

Coffee consumption has been suggested to confer protective effects against major depressive disorder （MDD）; however, the underlying mechanisms remain unclear. This study examined whether coffee and caffeine intake are associated with gut microbiota composition in individuals with MDD. We analyzed the gut microbiota of 32 patients with MDD and 34 healthy controls using 16S rRNA gene sequencing. Dietary intake, including caffeine and coffee consumption, was estimated using the Brief-Type Self-Administered Diet History Questionnaire. Depression severity was assessed using the Hamilton Depression Rating Scale （HDRS） and the Montgomery-Åsberg Depression Rating Scale （MADRS）. In the MDD group, three bacterial taxa at the family level and 15 at the genus level were significantly correlated with depression severity scores. Among these taxa, a significant interaction was observed between depression status and caffeine intake on the relative abundance of Coriobacteriales Incertae Sedis （F ［1,62］＝10.322, uncorrected p＝0.002）. These findings suggest that caffeine consumption may be associated with specific gut microbiota in patients with MDD.

Previous studies suggest that the gut microbiota may contribute to the onset of depression and that dairy consumption may affect the gut microbiota and alleviate depressive symptoms. This study aimed to investigate the relationship between dairy consumption, gut microbiota composition, and its metabolites in patients with major depressive disorder （MDD）. Fecal samples were collected from 32 participants with MDD and 34 age- and sex-matched healthy controls （HCs）. The gut microbiota composition and its metabolites were analyzed. Dairy intake was evaluated using the Brief-Type Self-Administered Dietary History Questionnaire. Depression severity was assessed using the Hamilton Depression Rating Scale （HDRS）. The effects of depression status （MDD versus HC groups） and dairy intake on the gut microbiota were examined using a two-way analysis of variance. We found interactions between the effects of depression status and dairy intake on the abundance of the family Lactobacillaceae （F ［1,62］＝4.265, uncorrected p＝0.043） and the genera Lactobacillus （F ［1,62］＝4.044, uncorrected p＝0.049） and Megasphaera （F ［1,62］＝5.739, uncorrected p＝0.020）. Additionally, pelargonate concentrations were correlated with depression severity （HDRS score: rs＝−0.375, uncorrected p＝0.034） and dairy intake （rs＝0.363, uncorrected p＝0.041）. Dairy consumption may be associated with specific gut microbiota and its metabolites in patients with MDD. Further large-scale studies are required for in-depth char­ac­ter­i­za­tion of the relationship between dairy intake and gut microbiota and its metabolomes in patients with MDD.

Background: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Methods: Children aged 6–12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non‐related neurotypical volunteers were recruited cross‐sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule‐2 (ADOS‐2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha‐diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non‐related neurotypical controls. Results: Ninety‐eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non‐related neurotypical controls). The alpha‐diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed‐effect model ( F (4, 93) = 4.539, p = .02), ( F (4, 93) = 3.185, p = .017), respectively. In a post‐hoc pairwise comparison, patients with ASD had lower alpha‐diversity compared with non‐related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups ( F (4, 84) = 1.494, p = .211). Conclusions: Our study indicates disorder‐specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co‐occurrence, and strictly control for background information such as diet, to elucidate the gut–microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

Brexpiprazole （BREX）, a serotonin-dopamine activity modulator, was launched in Japan in 2018. The medium- to long term adherence to this medication and the incidence of side effects are not well characterized. BREX is also a potent partial agonist of human serotonin 5-HT1A, which produces anxiolytic effects. Therefore, we retrospectively examined the treatment persistence, the incidence of adverse effects, and the pre and posttreatment changes in the dose of benzodiazepines （BZDs） in patients with acute schizophrenia treated with BREX. This was an observational, retrospective study based on the medical records of patients hospitalized at Showa University Karasuyama Hospital between August 2018 and December 2021. Eighty-six patients who were diagnosed with schizophrenia based on the International Classification of Diseases and Related Health Problems, 10th Revision （ICD-10） definition and were prescribed BREX for the first time were included in the study. The mental status was assessed by clinicians using the Clinical Global Impression-Severity of Illness （CGI-S） scale. The continuation rate for BREX treatment during the first 24 weeks was 46.5％. Patients receiving BREX monotherapy at 24 weeks and those with a CGI-S score ≤ 5 at the start of BREX treatment had a higher persistence rate of BREX at 24 weeks. There were no significant differences between the BREX continuation and BREX discontinuation groups with respect to the dose change of BZDs. BREX monotherapy and mild-moderate mental status at initiation are potential predictors of BREX treatment persistence. Prospective studies are required to confirm these findings.

Background: Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study. Methods: Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20). Results: The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group. Conclusions: Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

We aimed to investigate the impact of aging on the relationship among the composition of gut microbiota, gastrointestinal (GI) symptoms, and the course of treatment for major depressive disorder (MDD) by analyzing the datasets from our previous study. Patients with MDD were recruited, and their stools were collected at three time points (baseline, midterm, and endpoint) following the usual antidepressant treatment. Gut microbiota were analyzed using 16S rRNA gene sequencing. Patients were categorized into two groups based on their age: the late-life group over 60 years and the middle-aged group under 60 years. GI symptoms were assessed with scores of item 11 of the Hamilton Anxiety Rating Scale. One hundred and ninety samples were collected from 32 patients with MDD. Several gut microbes had higher relative abundances in the late-life group than in the middle-aged group. In addition, the late-life group showed significantly higher diversity in the Chao1 index at baseline compared with the middle-aged group. We further found possible microbial taxa related to GI symptoms in patients with late-life depression. The abundance of several bacterial taxa may contribute to GI symptoms in the late-life depression, and our findings suggest that the therapeutic targets for the application of gut microbiota may differ depending on the age group of patients with depression.