World Journal of Biological Psychiatry最新文献

Introduction: Bipolar affective disorder (BD) is a chronic psychiatric illness characterized by alternating manic and depressive episodes. Despite extensive research, its underlying mechanisms remain unclear. Recent studies suggest that purinergic signaling and inflammation may play key roles in BD pathophysiology. This study aimed to explore biomarkers related to these systems to improve understanding of BD and identify potential diagnostic and prognostic indicators.

Methods: The study included 76 BD patients and 20 healthy controls from the Department of Adult Psychiatry, Poznan University of Medical Sciences. Blood samples were collected during acute episodes and after symptom remission. Biomarkers analyzed included uric acid (UA), interleukin-6 (IL-6), NACHT, P2X7 receptor, adenosine deaminase (ADA), xanthine dehydrogenase (XDH), and adenosine (ADO), measured by ELISA.

Results: NACHT (p = 0.004) and P2X7 (p = 0.001) were significantly higher post-treatment. Age positively correlated with NACHT, and BMI with UA. P2X7 levels negatively correlated with depressive symptom improvement. Gender differences revealed higher pre-treatment ADA levels in women and greater post-treatment increases in NACHT, ADA, and XDH in men. IL-6 was elevated during depressive episodes, while NACHT and XDH were higher in manic states. ROC analysis indicated strong diagnostic potential for XDH (AUC=0.917) and ADA (AUC=0.903). Logistic regression identified post-treatment NACHT and P2X7 as significant BD predictors.

Conclusions: The study highlights the involvement of purinergic and inflammatory pathways in BD pathophysiology. Biomarkers such as NACHT, P2X7, ADA, and XDH may aid in diagnosing BD and monitoring treatment responses, offering potential for biologically informed therapies.

Objectives: In light of the frequent co-occurrence of metabolic syndrome (MetS) in schizophrenia and their common links to oxidative stress, the aim of our study was to evaluate glutathione (GSH) metabolism parameters in patients with schizophrenia and MetS.

Methods: The study cohort comprised two groups: (1) 60 patients with schizophrenia and MetS and (2) 70 patients with schizophrenia without MetS,. GSH and its fractions concentration, and GSH-enzymes activity in serum were determined spectrophotometrically.

Results: Total GSH and oxidised GSH (GSSG) concentration was significantly higher in schizophrenia patients with MetS (p = 0.003 and p = 0.028 respectively) than in those without MetS. The rGSH/GSSG ratio was significantly reduced in schizophrenia patients with MetS relative to those without MetS (p = 0.022). Glutathione S-transferase (GST) activity was significantly higher in patients with MetS than in those without MetS (p = 0.019).

Conclusions: The findings of this study suggest that MetS in schizophrenia patients is associated with GSH metabolism dysregulation.

Introduction: Suicidal behaviour, including completed suicide and attempted suicide, is affected by genetic factors, involving serotonergic system genes. TPH2 gene encodes tryptophan hydroxylase 2, rate-limiting brain serotonin synthetising enzyme whose pre-mRNAs are edited by ADAR enzymes, including ADARB1. TPH2 rs4290270 and ADARB1 rs9983925/rs4819035 variants have been previously implicated in suicide attempt in Serbian psychiatric patients. Our aim was to investigate whether these variants could also contribute to genetic predisposition for a more extreme phenotype-completed suicide differentiated by violent and non-violent method-in a Slovenian cohort.

Methods: Genotyping of TPH2 rs4290270 and ADARB1 rs9983925/rs4819035 was performed on sample including 333 suicide completers (305 violent and 28 non-violent), and 357 non-suicidal autopsy controls from Slovenia. Statistical analyses were performed in PLINK ver. 1.9.

Results: TPH2 rs4290270 AA genotype increased the risk of completed suicide compared to controls (p = 0.032/0.031^corrected), mainly driven by violent suicide (p = 0.045/0.044^corrected). Preliminary, ADARB1 rs4819035 GT and GG genotypes increased the risk of non-violent completed suicide compared to controls (p = 0.015/0.011^corrected), and to violent completed suicide (p = 0.026/0.022^corrected).

Conclusion: TPH2 and ADARB1 genetic variants shape different genetic backgrounds in different types of suicidal behaviour, completed and attempted suicide. Preliminary, these variants might also differentiate between various methods of completed suicide, violent and non-violent.

Objectives: Treatment-resistant depression (TRD) poses a major challenge in research and clinical practice. Various guidelines recommend different pharmacological approaches. While lithium and second-generation antipsychotics have traditionally been the drugs of choice in cases of medication resistance, recent years have seen increasing evidence for the efficacy of esketamine as a fast-acting agent against depression. Although there is a large body of meta-analytical evidence, direct comparisons between the agents are scarce.

Methods: A systematic review of databases was conducted for randomised and naturalistic head-to-head studies comparing augmentation with lithium, quetiapine, or (es)ketamine in adults with TRD was included. Findings from relevant meta-analyses were integrated qualitatively.

Results: We found four studies, comprising three trials comparing lithium and quetiapine and one comparing esketamine and quetiapine. In summary, (1) all three agents are effective, (2) there may be a descriptive superiority of esketamine over quetiapine and of quetiapine over lithium.

Conclusions: The results generally argue for a re-evaluation of existing treatment algorithms in guidelines. However, since all three are fundamentally different molecules with different pharmacokinetic and pharmacodynamic properties and differ in (1) side effects and contraindications as well as (2) profile focus, embedding them in a comprehensive clinical context is important.

Objectives: Existing studies on obsessive-compulsive disorder (OCD) typically use single imaging metrics or resting-state functional connectivity, limiting insight into the directional brain information flow.

Methods: Imaging data for 93 OCD patients and 96 healthy controls (HC) were analysed. Between-group differences in fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) identified common discrepant brain regions, used as seed points for whole-brain effective connectivity (EC) analysis via granger causality.

Results: Compared to HC, patients with OCD exhibited reduced fALFF in the left inferior occipital gyrus (L_IOG) and postcentral gyrus, elevated fALFF in the left caudate nucleus, and reduced ReHo in the L_IOG and right calcarine sulcus. EC from the right caudate nucleus to the L_IOG was attenuated, while that from the right supramarginal gyrus to the L_IOG was enhanced. Furthermore, diminished connectivity was observed from the L_IOG to the right middle frontal gyrus, middle occipital gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus (R_PoCG). Among them, fALFF value of the L_IOG and its EC value to the R_PoCG were positively correlated with OCD symptom severity.

Conclusions: The L_IOG may function as a pivotal integrative node spanning sensorimotor and executive control networks, contributing to the pathological mechanisms of OCD.

Spinal cord injury (SCI) markedly increases the risk of depression, affecting 16-30% of patients and contributing to elevated mortality. In this study, we used UK Biobank data to explore the relationship between SCI and depression, with a particular focus on structural brain changes as potential mediators. Cox regression models, adjusted for sociodemographic and lifestyle factors, demonstrated that participants with SCI had a significantly higher incidence of depression than those without, with the effect more pronounced in women. Genetic predisposition further intensified the risk, with SCI associated with a 2.1-fold, 2.7-fold, and 3.6-fold increase in depression risk at low, medium, and high polygenic risk score levels, respectively. Neuroimaging analysis revealed cortical thinning in frontal areas, ventricular enlargement, and thalamic signal intensity changes, while mediation analysis indicated that brain structural alterations accounted for 6-9% of depression risk after SCI, particularly involving the right S. interm. prim. Jensen, left lateral ventricle, and thalamus. These findings underscore the complex interplay of structural brain changes, sex differences, and genetic susceptibility in mediating depression risk following SCI, and suggest potential targets for therapeutic intervention.

Background: Polycystic ovary syndrome (PCOS) and primary ovarian insufficiency (POI) are significant causes of female infertility. Women with schizophrenia exhibit reduced fertility, and existing research indicates associations between schizophrenia and PCOS, though causality remains uncertain. Furthermore, the relationship between schizophrenia and POI has not been elucidated.

Methods: The study utilised Genome-wide association study (GWAS) data from Psychiatric Genomics Consortium (PGC) database and European populations (schizophrenia: n = 127,906; PCOS: 642 cases, 118,228 controls; POI: 254 cases, 1,182,288 controls). Single-nucleotide polymorphisms (SNPs) of genome-wide significance were selected as instrumental variables (IVs). Various sensitivity analyses were employed to validate the causality between schizophrenia and PCOS/POI.

Results: Schizophrenia increased the risk of PCOS (OR= 1.070, 95% CI: 1.024 to 1.119, p = 0.002), and had a potential causal relationship with POI (OR= 1.316, 95% CI: 1.011 to 1.713, p = 0.041). These results were robust in sensitivity analysis, with no heterogeneity or pleiotropy detected.

Conclusion: These results reveal the potential mechanisms underlying reduced fertility in schizophrenia and provide a novel perspective on the link between psychiatry and reproductive endocrinology, motivating further investigation. Meanwhile, this study underscores the clinical imperative for enhanced surveillance of ovarian function and timely fertility assessment in patients to optimise outcomes.

Background: Innate immune dysfunction is implicated in schizophrenia (SZ) and bipolar disorder (BD). Alterations in natural killer (NK) cells, monocytes and macrophages occur in both disorders across peripheral and central compartments. This systematic review synthesises current evidence by clinical stage and illness phase.

Methods: Following PRISMA guidelines, PubMed, Scopus and PsycINFO were searched to May 2025. Eligible studies reported peripheral blood, cerebrospinal fluid (CSF) or post-mortem brain findings.

Findings: Eighty-one studies met inclusion criteria. In SZ, peripheral data showed altered NK cell subsets and monocyte abnormalities, including elevated counts and inflammatory ratios, particularly in early or acute stages. CSF studies found increased monocyte chemoattractants, and post-mortem analyses revealed macrophage upregulation in frontal and temporal cortices. In BD, NK cell results were limited and inconsistent. Monocyte activation was most evident during symptomatic phases, particularly mania. CSF analyses detected increased monocyte- and macrophage-associated proteins, while post-mortem findings indicated microglial activation in selected cortical and subcortical regions, less consistently than in SZ.

Interpretation: Innate immune alterations in SZ and BD partly overlap yet remain disorder- and state-specific. Central compartments and NK cells are underexplored. Stratification by stage and phase may improve interpretability and guide longitudinal, multimodal, cell-specific research for precision immunopsychiatry.

Objectives: Maternal separation (MS) is a well-established risk factor for psychological disorders like depression. Alterations in the blood-brain barrier (BBB) and its tight junction proteins, such as claudins (CLDNs), may contribute to the pathophysiology of depression. Environmental enrichment (EE) has shown antidepressant-like effects, though its exact underlying mechanisms remain incompletely understood. This study aimed to assess the effect of EE on depressive-like behaviours induced by MS in male mice, centring on hippocampal CLDNs.

Methods: Thirty-two male NMRI mice were randomly divided into control (C), MS, MS+EE, and C + EE groups. The MS paradigm was conducted from postnatal day (PND) 2 to 14. EE was implemented between PND 45 and 60. Behavioural tests, including the open field (OFT), forced swimming (FST), and splash tests, were performed. qRT-PCR was performed to evaluate the hippocampal expression of CLDN-1, CLDN-5, and CLDN-12.

Results: MS induced depression-like behaviours, as an increase in immobility time in the FST and a decrease in grooming activity time in the splash test. MS increased the expression of CLDN-1, CLDN-5, and CLDN-12 in the hippocampus. EE significantly reduced depressive-like behaviours and downregulated CLDN-1 and CLDN-12 gene expression, while CLDN-5 overexpressed.

Conclusions: EE exerts antidepressant-like effects, potentially through modulation of BBB-associated CLDNs.

Background: This study aimed to assess the risk of major psychiatric and neurodevelopmental disorders in first degree relatives (FDRs) of individuals with panic disorder (PD), including PD, bipolar Disorder (BD), major depressive disorder (MDD), schizophrenia, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD).

Material and methods: Between 2001 to 2010, we included 153,091 FDRs of individuals with PD and 1:4 matched controls based on age and sex from the Taiwan National Health Insurance Research Database. Poisson regression model with a robust error variance to estimate the relative.

Results: After adjusting for demographics and psychiatric disorders, FDRs of individuals with PD had a higher risk of PD (reported as adjusted relative risk with 95% confidence interval: (ARR:2.74, 95%CI: 2.56 to 2.93), BD (ARR:1.24, 95%CI: 1.15 to 1.34), MDD (ARR: 1.46, 95%CI: 1.40 to 1.53), ADHD (ARR: 1.25, 95%CI: 1.18 to 1.32), and OCD (ARR:1.54, 95%CI:1.40 to 1.69) compared to their matched controls.

Conclusion: Our findings may aid in counselling and early awareness of major psychiatric and neurodevelopmental disorders. Future genetic and population studies are needed to investigate the underlying mechanisms and confirm our findings.