Background Toxoplasma gondii (T. gondii) infection has been implicated in the pathophysiology of psychiatric disorders, yet no study has compared its seroprevalence between schizoaffective disorder (SZA) and other psychiatric conditions. This study aimed to compare T. gondii seroprevalence between patients with SZA, schizophrenia (SZ), and bipolar disorder (BD), and to examine whether seropositivity differentially affects innate immune markers across these diagnoses. Methods Overall 144 patients were included in this cross-sectional study. T. gondii seroprevalence was determined and leukocyte counts and derived immune ratios were compared across diagnostic groups according to T.gondii seroprevalence. Results T. gondii seroprevalence was significantly higher in SZA (68.8%) as compared to BD (44.2%; p = 0.02), but did not differ significantly from SZ (52.2%; p = 0.2). Relative to SZA, higher neutrophil (p < 0.01) and monocyte (p = 0.02) levels were associated with greater odds of BD, while higher NLR was associated with both BD (p = 0.04) and SZ (p = 0.02), and higher MLR with SZ (p = 0.02). However, none of these associations remained significant after Bonferroni correction. We observed a significant interaction between basophil counts and T. gondii in SZA versus BD (padj < 0.01) and SZ (padj < 0.01), indicating a diagnosis-specific immune modulation. Conclusion Our findings suggest that T. gondii seroprevalence in SZA is closer to SZ than BD. However, seropositivity appears to affect innate immune markers differently in SZA, without inflammatory activation. This immune profile suggests a unique pathophysiological signature in SZA and warrants further investigation.
Background Formal thought disorder (FTD) is a core dimension of schizophrenia, which has been associated in previous studies with increased brain functional connectivity between temporal gyri and striatal regions as measured with fMRI. Cannabis use is highly prevalent in schizophrenia population as compared with the general population and, in the context of elevated tetrahydrocannabinol/cannabidiol (THC/CBD) ratio, has been found to be associated with increased FTD in schizophrenia. Consequently, in this study, we aimed to investigate whether cannabis consumption in patients with schizophrenia is generally associated with both enhanced functional connectivity and FTD. Methods We explored the functional connectivity between the temporal gyri and striatal regions in 51 schizophrenia patients divided into two groups stratified by cannabis use. FTD was measured using the conceptual disorganization item from the Positive And Negative Syndrome Scale. Region-of-interest (ROI)-to-ROI and seed-based connectivity analyses, correlation tests, and mediation models were conducted using both frequentist and Bayesian approaches. Results No significant difference was found in terms of functional connectivity between cannabis users and non-users. THC/CBD ratio was not significantly associated with cortico-striatal connectivity or FTD. Overall, Bayesian results indicated moderate to strong evidence favoring the null hypothesis across most models. Conclusion Cannabis use was not robustly associated with an altered cortico-striatal connectivity in this sample. The convergence of frequentist and Bayesian evidence suggests that cannabis use may not account for previously reported FTD-related connectivity alterations in schizophrenia. Larger studies considering cannabis composition, dose-response relationships, and symptom dimensions are warranted to refine these findings.
Racial disparities in emergency department (ED) use among patients with schizophrenia may reflect differences in treatment access and continuity after antipsychotic initiation. We examined whether oral antipsychotic availability or administering long-acting injectable antipsychotics, measured by proportion of days covered (PDC) using claims data, mediated the association between race and ED use and whether mediation differed by antipsychotic class and route of administration. Using South Carolina Medicaid claims from 2004 to 2019, we identified 1666 adults with schizophrenia or schizoaffective disorder initiating antipsychotic treatment with 12-month washout period. PDC was measured during the first 6 months after treatment initiation. The outcome was any ED visit during the subsequent 6 months. Mediation analysis was conducted overall and by antipsychotic subgroup. Black beneficiaries had higher ED use than White beneficiaries (33% vs. 27%, p = 0.03) and lower PDC (mean 0.45 vs. 0.55, p < 0.0001). In unadjusted analyses, PDC mediated 23% of the association between race and ED use (95% CI 8%–94%, p = 0.03). After covariate adjustment, PDC mediated 25% of the association (95% CI 10%–95%, p = 0.006). Significant mediation was observed among oral antipsychotic users (28%, p = 0.02), second-generation antipsychotic users (29%, p = 0.008), and most prominently in oral second-generation antipsychotic users (30%, p = 0.006). No significant mediation was observed among first-generation antipsychotic or long-acting injectable users. These findings suggest that antipsychotic availability and administration may be one pathway contributing to racial disparities in acute psychiatric care.
Background The five canonical domains of negative symptoms in schizophrenia — blunted affect, alogia, asociality, anhedonia, and avolition — were established by a consensus process. Meta-analyses have placed psychomotor retardation (PMR) rating scale items in negative symptom factors, suggesting it may be a sixth negative symptom domain. Methods We pooled data from two cross-sectional, multicenter, international studies of schizophrenia (N = 271) and used PANSS item G7 (Motor Retardation) as a measure of PMR. In multivariate analyses we examined G7 as a predictor of cognitive function, personal and social function, and negative symptoms other than PMR. We also examined whether G7 mediated the association between extrapyramidal symptoms and negative symptoms. Results In some analyses the G7 factor had relationships characteristic of the five canonical domains: correlations with those negative symptoms and negative correlations with function and cognition. However, other findings were consistent with its classification as a motor symptom: significant correlations with the PANSS Mannerism and Posturing item and with extrapyramidal symptoms, and mediation of the relationship between extrapyramidal symptoms and the canonical negative symptoms. There was no significant relationship with self-reported hours of sleep. Conclusions PMR showed associations with negative symptoms, cognitive impairment, and functional outcome, consistent with status as a sixth negative symptom domain. However, other findings leave unclear whether it should be considered a negative symptom, a motor symptom, or something more complex. Problems in the G7 item definition and description contribute to this uncertainty.
Schizophrenia patients compared to controls show reduced physical and cognitive effort allocation despite higher rewards offered. Negative symptoms, cognitive control deficits, and functional impairments are all implicated in reduced effort allocation, suggesting compromised cognitive-reward systems drive patient outcomes. However, patterns and predictors of decisions to expend different types of effort remain underexplored in early psychosis (EP). This study investigated predictors of effort allocation in 34 EP outpatients. We used Generalized Estimating Equations to evaluate the following as predictors of decisions to expend effort: (1) changes in reinforcement environment (reward, probability, expected value), and (2) patient characteristics (expressive and motivation/pleasure symptoms, cognitive control). Assessments included the Effort Expenditure for Rewards Task (physical), a parallel cognitive effort task adapted by our team, AX-Continuous Performance Test, and clinical symptom interviews (e.g., Brief Negative Symptom Scale). Patients modulated physical effort based on integrated assessments of reward and probability. Cognitive control, measured as the proactive maintenance of goal-relevant information and resources, predicted physical effort expenditure, but only at low expressive symptom severity. In contrast, patients showed inefficient effort modulation and a risk-aversive probabilistic assessment on the cognitive effort task. By early psychosis, patients exhibit conservative cognitive effort allocation, disregarding high-value rewards, despite intact capacity. Our findings indicated that negative symptoms and cognitive control had a minimal direct influence on effort decisions in early psychosis. This suggests that the illness burden in early stages may be less pronounced than in chronic psychotic illness, potentially leading to different mechanistic pathways for effort allocation.
