Schizophrenia (Heidelberg, Germany)最新文献

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.

Aberrant motor-sensory predictive functions have been linked to symptoms of psychosis, particularly reduced attenuation of self-generated sensations and misattribution of self-generated actions. Building on the parallels between prediction of self- and other-generated actions, this study aims to investigate whether individuals with psychosis also demonstrate abnormal perceptions and predictions of others' actions. Patients with psychosis and matched controls completed a two-alternative object size discrimination task. In each trial, they observed reaching actions towards a small and a large object, with varying levels of temporal occlusion ranging from 10% to 80% of movement duration. Their task was to predict the size of the object that would be grasped. We employed a novel analytic approach to examine how object size information was encoded and read out across progressive levels of occlusion with single-trial resolution. Patients with psychosis exhibited an overall pattern of reduced and discontinuous evidence integration relative to controls, characterized by a period of null integration up to 20% of movement duration, during which they did not read any size information. Surprisingly, this drop in accuracy in the initial integration period was not accompanied by a reduction in confidence. Difficulties in action prediction were correlated with the severity of negative symptoms and impaired functioning in social relationships.

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = -0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

Autonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.

Clozapine is the gold standard for treating treatment-resistant schizophrenia although continuously underutilized. Previous surveys of clinicians have found that some of the most frequently cited barriers to clozapine prescribing are related to the blood-monitoring requirements. However, these surveys tend to explore general perspectives and may not reflect the true impact of different barriers in real-world outpatient settings. This study aimed to explore this issue. First, by surveying the clinicians responsible for the treatment of 39 clozapine-eligible, yet clozapine-naive, outpatients with schizophrenia. Then, based on the survey results, explanatory interviews with the participating psychiatrists were conducted and analyzed thematically. The most frequently cited reason for non-prescribing of clozapine was the expected non-compliance with blood-monitoring requirements; however, overall stability and/or severe mental illness was chosen as the most important reason in most patient-cases. The qualitative analysis highlighted the combined impact of standard clinical practice, personal experiences, and organizational constraints on clozapine utility.

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.

Evidence on the associations between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia is lacking. This study aimed at explore the underlying mechanisms between patient's disability and caregiver burden among Chinese family caregivers of individual living with schizophrenia. A cross-sectional study was carried out in four Chinese cities (Wuhan, Changsha, Guangzhou, and Shenzhen), between April, 2021 and March, 2022. A total of 493 patients and their family caregivers were invited to report related data. The Zarit burden interview, WHODAS 2.0, the Potentially harmful behavior scale, the Affiliate Stigma Scale, and the Multidimensional Scale of perceived social support were used to collect data. Linear regression analysis and bootstrapping analysis were conducted. The adjusted regression results showed that patients' disability (B = 0.616; 95% CI: 0.479-0.753), potentially harmful behavior on caregivers (B = 0.474; 95% CI: 0.232-0.716), and caregiver's low social support (B = -0.079; 95% CI: -0.158- -0.002), high level of affiliate stigma (B = 13.045; 95% CI: 10.227-15.864) were associated with higher level of caregiver burden (p < 0.05). In the mediation model, the direct path from patient's disability to caregiver burden (B = 0.428, β = 0.371, p < 0.001) was significant and positive. Patient's disability was indirectly associated with caregiver burden through patient's potentially harmful behavior, caregiver's affiliate stigma, and social support, the standardized regression coefficients ranged from 0.026-0.049 (p < 0.05). Patient's potentially harmful behavior, caregiver's affiliate stigma, and social support mediated the relationship between patients' disability and caregiver burden. Future intervention studies designed to target these three factors may be beneficial for family caregivers of persons living with schizophrenia.

Clozapine-induced fever marks the beginning of its inflammatory and potentially life-threatening adverse effects, such as myocarditis. We retrospectively analyzed the correlation between clozapine titration rate and fever onset date in 254 Japanese patients, including 55 with treatment-resistant schizophrenia who developed clozapine-induced fever. Pearson's product-moment correlation indicated a significant delay in the fever onset date with slower titration. Most fever onset cases occurred within 4 weeks, even with slow titration. Therefore, clinicians should remain vigilant in monitoring clozapine-induced fever within 4 weeks of clozapine initiation, regardless of the titration rate.

Changes in dopamine and fronto-striato-thalamic (FST) circuit functional connectivity are prominent in schizophrenia. Dopamine is thought to underlie connectivity changes, but experimental evidence for this hypothesis is lacking. Previous studies examined the association in some of the connections using positron emission tomography (PET) and functional MRI (fMRI); however, PET has disadvantages in scanning patients, such as invasiveness. Excessive dopamine induces neuromelanin (NM) accumulation, and NM-MRI is suggested as a noninvasive proxy measure of dopamine function. We aimed to investigate the association between NM and FST circuit connectivity at the network level in patients with schizophrenia. We analysed substantia nigra NM-MRI and resting-state fMRI data from 29 schizophrenia patients and 63 age- and sex-matched healthy controls (HCs). We identified the FST subnetwork with abnormal connectivity found in schizophrenia patients compared to that of HCs and investigated the relationship between constituting connectivity and NM-MRI signal. We found a higher NM signal (t = -2.12, p = 0.037) and a hypoconnected FST subnetwork (FWER-corrected p = 0.014) in schizophrenia patients than in HCs. In the hypoconnected subnetwork of schizophrenia patients, lower left supplementary motor area-left caudate connectivity was associated with a higher NM signal (β = -0.38, p = 0.042). We demonstrated the association between NM and FST circuit connectivity. Considering that the NM-MRI signal reflects dopamine function, our results suggest that dopamine underlies changes in FST circuit connectivity, which supports the dopamine hypothesis. In addition, this study reveals implications for the future use of NM-MRI in investigations of the dopamine system.