NPJ Schizophrenia最新文献

Cognitive impairment is a core symptom of schizophrenia (SZ), with GABAergic dysfunction in the brain potentially serving as a critical pathological mechanism underlying this condition. Intracortical inhibition (ICI), which includes short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), can be used to assess the inhibitory function of cortical GABAergic neurons. The aim of this study was to investigate the relationship between ICI and cognitive function, as well as psychopathological symptoms, in SZ patients. We recruited 130 SZ patients and 105 healthy controls (HCs). All subjects underwent paired-pulse transcranial magnetic stimulation (ppTMS) measurements, which included resting motor threshold (RMT), SICI and LICI. The cognitive function of all subjects was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). The psychopathological symptoms of the SZ group were assessed using the Positive and Negative Syndrome Scale (PANSS). We examined group differences in MCCB scores, RMT, SICI, and LICI. Within the SZ group, we assessed the relationship between ICI and cognitive function, as well as psychopathological symptoms. Two-way ANOVA, Mann–Whitney U test, Receiver operating characteristic (ROC) curves, and partial Spearman correlation analysis were performed. The SZ group showed a worse cognitive score in all 6 cognitive dimensions of the MCCB compared to the HC group (all p < 0.05). The SZ group had lower degree of SICI and LICI compared to the HC group (both p < 0.05). ROC curves analysis showed that SICI and LICI all displayed good performance in differentiating SZ patients and HCs (both p < 0.05), and SICI exhibited a better performance, yielding an area under the curve (AUC) of 0.856 (95% CI 0.807–0.904). Furthermore, in the SZ group, SICI demonstrated a significant negative correlation with PANSS positive score, negative score, general psychopathology score, and total score (all p_Bonferroni < 0.05), and LICI demonstrated a significant negative correlation with PANSS positive score, general psychopathology score and total score (all p_Bonferroni < 0.05). Additionally, in the SZ group, SICI demonstrated a significant positive correlation with speed of processing score, working memory score, verbal learning score, visual learning score, and reasoning and problem-solving score of the MCCB (all p_Bonferroni < 0.05), while LICI was only weakly positive correlated with speed of processing score of the MCCB (r = 0.247, p = 0.005, p_Bonferroni = 0.03). Our results demonstrate that the reduction of ICI could serve as a trait-dependent in-vivo biomarker of GABAergic deficits for SZ and related cognitive impairments.

Previous studies that focused on univariate correlations between neuroanatomy and cognition in schizophrenia identified some inconsistent findings. Moreover, antipsychotic medication may impact the brain-behavior profiles in affected individuals. It remains unclear whether unmedicated and medicated individuals with schizophrenia would share common neuroanatomy-cognition associations. Therefore, we aimed to investigate multivariate neuroanatomy-cognition relationships in both groups. A sample of 59 drug-naïve individuals with first-episode schizophrenia (FES) and a sample of 115 antipsychotic-treated individuals with schizophrenia were finally included. Multivariate modeling was conducted in the two patient samples between multiple cognitive domains and neuroanatomic features, such as cortical thickness (CT), cortical surface area (CSA), and subcortical volume (SV). We observed distinct multivariate correlational patterns between the two samples of individuals with schizophrenia. In the FES sample, better performance in token motor, symbol coding, and verbal fluency tests was associated with greater thalamic volumes but lower CT in the prefrontal and anterior cingulate cortices. Two significant multivariate correlations were identified in antipsychotic-treated individuals: 1) worse verbal memory performance was related to smaller volumes for the most subcortical structures and smaller CSA mainly in the temporal regions and inferior parietal lobule; 2) a lower symbol coding test score was correlated with smaller CSA in the right parahippocampal gyrus but greater volume in the right caudate. These multivariate patterns were sample-specific and not confounded by imaging quality, illness duration, antipsychotic dose, or psychopathological symptoms. Our findings may help to understand the neurobiological basis of cognitive impairments and the development of cognition-targeted interventions.

A subgroup of schizophrenia cases with elevated inflammation have reduced neurogenesis markers and increased macrophage density in the human subependymal zone (SEZ; also termed subventricular zone or SVZ) neurogenic niche. Inflammation can impair neurogenesis; however, it is unclear which other pathways are associated with reduced neurogenesis. This research aimed to discover transcriptomic differences between inflammatory subgroups of schizophrenia in the SEZ. Total RNA sequencing was performed on SEZ tissue from schizophrenia cases, designated into low inflammation (n = 13) and high inflammation (n = 14) subgroups, based on cluster analysis of inflammation marker gene expression. 718 genes were differentially expressed in high compared to low inflammation schizophrenia (FDR p < 0.05) and were most significantly over-represented in the pathway ‘Hepatic Fibrosis/Hepatic Stellate-Cell Activation’. Genes in this pathway relate to extracellular matrix stability (including ten collagens) and vascular remodelling suggesting increased angiogenesis. Collagen-IV, a key element of the basement membrane and fractones, had elevated gene expression. Immunohistochemistry revealed novel collagen-IV+ fractone bulbs within the human SEZ hypocellular gap. Considering the extracellular matrix’s regulatory role in SEZ neurogenesis, fibrosis-related alterations in high inflammation schizophrenia may disrupt neurogenesis. Increased angiogenesis could facilitate immune cell transmigration, potentially explaining elevated macrophages in high inflammation schizophrenia. This discovery-driven analysis sheds light on how inflammation may contribute to schizophrenia neuropathology in the neurogenic niche.

Previous research has suggested a correlation between socioeconomic status (SES) and mental diseases, while personality traits may be associated with SES and the risk of mental disorders. However, the causal nature of these associations remains largely uncertain. Our Mendelian randomization (MR) study aims to explore the bidirectional causality between SES and mental disorders, as well as to evaluate the potential mediating role of personality in these associations. Using bidirectional MR approach, we assessed the causality between SES indicators and mental disorders. We then used a two-step MR method to further investigate whether and to what extent personality mediates the causal associations in Caucasians. The forward MR analyses identified that years of education, household income, age at first birth and the Townsend deprivation index had a causal association with at least one mental disorder. The reverse MR analyses identified causal effects of genetically predicted schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder on five SES indicators. Importantly, mediation analysis showed that neuroticism partly mediated the causality of household income and years of education on major depressive disorder, respectively. In brief, our study confirmed the bidirectional relationship between SES and mental disorders. We also revealed the role of neuroticism in mediating the association between SES and major depressive disorder, highlighting the importance of considering both socioeconomic and personality factors in mental health research and interventions.

Racial disparities in prescriptions of anti-psychotics have been highlighted before. However, (i) the evidence on other medications, including anti-depressant or mood stabilizing medications is lacking, and (ii) the role of potentially confounding factors and (iii) specificity of such disparities to schizophrenia (SCZ), are still unknown. We used electronic health records (EHRs) from 224,212 adults to estimate the odds ratios of receiving a prescription for different nervous system medications among patients with SCZ of different race/ethnicity, and analogous linear models to investigate differences in prescribed medication doses. To verify specificity of the observed patterns to SCZ, we conducted analogous analyses in depression and bipolar disorder (BD) patients. We found that Black/African American (AA) and Hispanic patients with SCZ were more likely to be prescribed haloperidol (Black/AA: OR = 1.52 (1.33–1.74); Hispanic: OR = 1.32 (1.12–1.55)) or risperidone (Black/AA: OR = 1.27 (1.11–1.45); Hispanic: OR = 1.40 (1.19–1.64)), but less likely to be prescribed clozapine (Black/AA: OR = 0.40 (0.33-0.49); Hispanic: OR = 0.45 (0.35-0.58)), compared to white patients. There were no race/ethnicity-related differences in the prescribed medication doses. These patterns were not specific to SCZ: Asian, Hispanic and Black/AA patients with BD or depression were more likely to be prescribed anti-psychotics, but less likely to be prescribed antidepressants or mood-stabilizers. In conclusion, we found racial/ethnic disparities in the medications prescribed to patients with SCZ and other psychiatric conditions. We discuss the potential implications for the quality of care for patients of diverse races/ethnicities.

Clozapine-resistant treatment-refractory schizophrenia (CR-TRS) patients face significant clinical challenges. While links between metabolic syndrome (MetS) and inflammatory cytokines in schizophrenia have been established, the relationship between MetS and cytokine levels in CR-TRS patients remains unexplored. This study aimed to investigate the relationship between cytokines levels, clinical symptoms and cognitive impairments in CR-TRS patients, both with and without MetS. The study included 69 CR-TRS patients (31with MetS and 38 without MetS) and 84 healthy controls. The levels of IL-2, IL-6, TNF-α and routine biochemical parameters were measured. Psychopathological symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. We found that CR-TRS patients with MetS displayed lower cognitive function scores compared to those without MetS, even when accounting for potential confounders. TNF-α levels were significantly higher in CRTRS patients with MetS compared to those without MetS, demonstrating substantial pathophysiological potential for CR-TRS patients with MetS via receiver operating characteristic curve (ROC). In CR-TRS patients without MetS, IL-2 independently contributed to the total score and general psychopathology subscore of PANSS. Additionally, IL-6 exhibited an independent contribution to the positive subscore of PANSS. In terms of cognition function, IL-6 independently contributed to the delayed memory of RBANS in CR-TRS patients without MetS. TNF-α could potentially serve as a predictive marker for distinguishing between CR-TRS patients with/without MetS, while IL-2 and IL-6 could independently contribute to psychopathological symptoms or cognitive function in CRTRS patients without MetS. Our study provided insights into the potential interplay between cytokines, clinical symptoms and cognitive impairments in CR-TRS patients with/without MetS.

Racial disparities in psychiatric diagnoses and treatment have significant public health implications, contributing to inequities in healthcare outcomes. We specifically examined racial disparities regarding pro re nata (PRN), or as needed, medications. Data from 14,616 encounters across 2019–2020 within Community Health Network’s inpatient psychiatric setting in Indianapolis, Indiana were included in this study. Due to the demographic sample size, analyses were narrowed to Black and White patients. Primary outcomes included comparisons across race for all PRN administrations and PRN administrations of antipsychotics vs. non-antipsychotics. Logistic regression was used to examine associations between race and PRN administrations by medication category, including all antipsychotics vs. non-antipsychotics overall, hydroxyzine, and lorazepam, independently. Significant differences in the percentage of administrations between Black and White patients were observed. Black patients received more PRN medications overall (71.0%) compared to White patients (67.7%) (p < 0.01). Further, while 17.7% of Black patients were administered PRN antipsychotics, this was true for only 8.2% of White patients (p < 0.001). When comparing antipsychotic PRNs with non-antipsychotic, hydroxyzine, and lorazepam PRNs, independently, Black patients were 58% (OR 1.58, p < 0.001), 109% (OR 2.09, p < 0.001), and 32% (OR 1.32, p < 0.001), more likely to receive antipsychotic PRNs, respectively, than White patients, controlling for sex, age, length of stay, and psychotic disorder diagnosis. Our study identifies yet another area of medical care with significant racial disparities. In this analysis of PRN medications during psychiatric admission, we identified significant differences in medication utilization by race. This information provides a basis for further investigation of disparities in patient-centered data.

Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H₂O₂), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H₂O₂ (F = 5.068, p = 0.008), ·OH (F = 31.856, p < 0.001), POD (F = 14.043, p < 0.001), α-toc (F = 3.711, p = 0.027), TAC (F = 24.098, p < 0.001), and MMP-9 (F = 3.219, p = 0.043) between TRS and CMS patients and healthy controls. For TRS patients, H₂O₂ levels were correlated to the PANSS positive subscale (r = 0.386, p = 0.032) and smoking (r = −0,412, p = 0.021), while TAC was significantly negatively correlated to the PANSS total score (r = −0.578, p = 0.001) and POD and TAC levels were positively correlated to body mass index (r = 0.412 and 0.357, p = 0.021 and 0.049, respectively). For patients with CMS, ·OH levels and TAC were positively correlated to the PANSS general subscale (r = 0.308, p = 0.031) and negatively correlated to the PANSS total score (r = −0.543, p < 0.001). Furthermore, H₂O₂, α-toc, and ·OH may be protective factors against TRS, and POD was a risk factor. Patients with CMS and TRS exhibit an imbalance in OS, thus warranting future investigations.

Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.

Cognitive impairment is common in people with schizophrenia (PWS). To detect the presence and its consequences, cognitive measures with sound psychometric properties are needed. However, these are lacking especially in low-income countries. Hence, we developed the Ethiopian Cognitive Assessment battery in Schizophrenia (ECAS). In this study, we evaluated the psychometric properties of the ECAS in a cross-sectional study involving 350 PWS. Confirmatory factor analysis demonstrated a one-factor solution. ECAS score correlated significantly but weakly with a disability measure (r = −0.13, p = 0.02) and symptom dimensions of PANSS (r between −0.12 and −0.29, p < 0.05), except for positive symptoms (r = −0.10, p > 0.05). Years of education (β = 0.12, 95% CI (0.09, 0.14), p < 0.001), male sex (β = 0.22, 95% CI (0.05, 0.39)), age β = −0.02, 95% CI (−0.03, −0.01), and medication side effects (β = −0.03, 95% CI (−0.06, −0.01), p = 0.021) were significantly associated with the composite score of ECAS. The Item Response Theory analysis showed that the tool best functions among participants with moderate cognitive impairment (difficulty coefficient between −1.12 and 0.27). The Differential Item Functioning analyses showed that education had a positive contribution on Digit Symbol Substitution Test (MH OR = 2.64, 95% CI (1.34, 5.20)). The results showed that ECAS is valid in assessing cognition in PWS in low-resource settings.