Chun-Hsin Chen

Depression, a common mood disorder, has been associated with gut microbiota alterations, though the underlying microbial mechanisms remain unclear. This study investigated potential gut microbiota biomarkers and functional pathways in 106 antidepressant-naïve depressive patients and 151 healthy controls, with careful of confounding factors. Stool samples were analyzed using 16S rRNA sequencing, revealing significantly lower alpha diversity and distinct beta diversity in depressive patients. Eleven taxa with differential abundance were identified, including Dialister and Lactococcus (decreased) and Hungatella, Sellimonas, and Lachnoclostridium (elevated), which may relate to gut inflammation and depressive symptom severity. Functional pathway analysis highlighted 36 altered pathways, including those involved in purine degradation, lipopolysaccharide biosynthesis, and amino acid metabolism. A random forest classification model built using the identified taxa achieved moderate accuracy (~0.72) in distinguishing depressive patients from controls. Additionally, we developed a novel Depression Dysbiosis Index (DDI), which positively correlated with depression severity and effectively differentiated between groups. The DDI was robust across analyses, emphasizing its potential clinical value. Future research should incorporate longitudinal designs, advanced sequencing techniques, and additional clinical factors to deepen our understanding of the gut-brain axis in depression and improve diagnostic and therapeutic strategies.

Background: Schizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug–drug interactions with anti-psychotics are prominent and complicated.Case presentation: We report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/μl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine.Conclusions: Neutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

The one-carbon metabolism pathway is a suitable candidate for studying the genetic and epigenetic factors contributing to metabolic abnormalities in patients with schizophrenia. We recruited 232 patients with schizophrenia and analyzed their serum folate, vitamin B12, and homocysteine levels and metabolic parameters to investigate the associations of genetic variants of methylenetetrahydrofolate reductase (MTHFR) and folate levels with metabolic parameters. MTHFR C677T and MTHFR A1298C were genotyped. Results showed that MTHFR 677T allele carriers had lower levels of total cholesterol and low-density lipoprotein cholesterol than those with the 677CC genotype. Metabolic parameters did not differ between MTHFR 1298C and 1298AA carriers. Patients with a low folate level had a lower high-density lipoprotein cholesterol level than those with a normal folate level, but the effect disappeared after adjustment for age, sex, and types of antipsychotics used. We found significant interactions between MTHFR A1298C and the folate level status (low vs. normal) in terms of body mass index and waist circumference. In conclusion, genetic variants in one-carbon metabolism might play a role in antipsychotic-induced metabolic abnormalities. Prospective studies on drug-naïve, first-episode patients with schizophrenia are warranted to identify key regions of DNA methylation changes accounting for antipsychotic-induced metabolic abnormalities.

Recent studies have suggested that gut–brain axis may be one of the mechanisms of major depression disorder (MDD). The current study aimed to investigate the effects of Lactobacillus plantarum PS128 (PS128) on psychophysiology in patients with MDD. We recruited 11 patients with MDD and gave them PS128 for 8 weeks. We compared depression symptoms, serum markers of inflammation and gut permeability, and gut microbiota before and after 8-week intervention and also explored the correlations among symptoms, biomarkers, and gut microbiota. After 8-week PS128 intervention, scores of Hamilton Depression Rating Scale-17 and Depression and Somatic symptoms Scale significantly decreased. Serum levels of high sensitivity c-reactive protein, interluekin-6, and tumor necrosis factor-α, zonulin and intestinal fatty acid binding protein, and the composition of gut microbiota did not significantly change after 8-week PS128 intervention. However, we found changes of some genera were correlated with changes of symptoms and biomarkers. In conclusion, this is an open trial with small sample size and has several limitations. The results need to be verified by randomized, double-blind, placebo-controlled trial with larger sample size.

Schizophrenia is a form of mental disorder that is behaviorally characterized by abnormal behavior, such as social function deficits or other behaviors that are disconnected from reality. Dysregulation of oxytocin may play a role in regulating the expression of schizophrenia. Given oxytocin’s role in social cognition and behavior, a variety of studies have examined the potential clinical benefits of oxytocin in improving the psychopathology of patients with schizophrenia. In this review, we highlight the evidence for the role of endogenous oxytocin in schizophrenia, from animal models to human studies. We further discuss the potential of oxytocin as a therapeutic agent for schizophrenia and its implication in future treatment.

Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo- or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.