Schizophrenia (Heidelberg, Germany)最新文献

An important goal in the treatment of patients with schizophrenia is remission in various domains, i.e., of symptoms, psychosocial functioning and subjective well-being. We undertook a post hoc analysis of pre-stabilized outpatients with schizophrenia and complete outcome data who had been enrolled in a 6-month non-interventional study of aripiprazole once-monthly (AOM) at 75 German sites. Key outcomes were (i) symptomatic remission (cross-sectional Andreasen et al. criteria (≤mild positive and negative key symptoms on the Brief Psychiatric Rating Scale (BPRS))); (ii) functional remission (Global Assessment of Functioning (GAF) scale score >70), and (iii) subjective well-being remission (WHO-5 scale score ≥13) at week 24. Of 242 enrolled patients, 194 (80.2%) (age = 43.9 ± 15.3 years; 51.5% male, illness duration = 14.0 ± 12.0 years) with complete data were analyzed. While 61.3% of the patients achieved symptomatic remission and 76.8% achieved remission regarding subjective well-being, only 24.7% achieved psychosocial functioning remission at 6 months. Remission rates were similar for men and women and across strata of disease duration with, on average, less remission in patients with longer illness duration. Correlations of improvements on the BPRS and GAF were weak, with the weakest correlation between the BPRS depressive mood item and the GAF scale, but similarly high correlation between BPRS subscales or the BPRS depressive mood item and subjective well-being. These findings suggest that while treatment with AOM can lead to symptomatic remission and remission regarding subjective well-being, additional interventions such as psychosocial therapy or supported employment and education may be necessary to achieve functional remission.

Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN⁺+TUNEL⁺ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.

Schizophrenia is a psychiatric disorder that is associated with various social dysfunctions, including shorter work hours. To measure the degree to which psychiatrists adhere to guidelines for pharmacological therapy of schizophrenia, we recently developed the individual fitness score (IFS) for adherence among psychiatrists in each patient. However, it remains unclear whether better adherence among psychiatrists is associated with higher patients' social functional outcomes, such as work hours. In this study, we examined the relationship between adherence to guidelines among psychiatrists and work hours in patients with schizophrenia. To evaluate the association between adherence to guidelines for pharmacological therapy among psychiatrists for treating schizophrenia and work hours, we used the IFS and social activity assessment, respectively, in 286 patients with schizophrenia. The correlation between IFS values and work hours was investigated in the patients. The adherence among psychiatrists to guidelines was significantly and positively correlated with work hours in patients with schizophrenia (rho = 0.18, p = 2.15 × 10^-3). When we divided the patients into treatment-resistant schizophrenia (TRS) and nontreatment-resistant schizophrenia (non-TRS) groups, most patients with TRS (n = 40) had shorter work hours (0-15 h/week). Even after excluding patients with TRS, the positive correlation between adherence to guidelines among psychiatrists and work hours in patients with non-TRS (n = 246) was still significant (rho = 0.19, p = 3.32 × 10^-3). We found that work hours were longer in patients who received the guideline-recommended pharmacotherapy. Our findings suggest that widespread education and training for psychiatrists may be necessary to improve functional outcomes in patients with schizophrenia.

The impact of psychological and physical health on quality of life (QoL) in patients with early psychosis remain relatively unexplored. We evaluated the predictive value of psychopathological and metabolic parameters on QoL in antipsychotic-naïve patients with first-episode psychosis before and after initial antipsychotic treatment. At baseline, 125 patients underwent assessments of psychopathology, prevalence of metabolic syndrome (MetS), and QoL. After 6 weeks of antipsychotic monotherapy, 89 patients were re-investigated. At baseline, the prevalence of MetS was 19.3% (n = 22). After 6 weeks, body weight (1.3 kg, p < 0.001) and body mass index (0.4 kg/m², p < 0.001) increased, and four additional patients developed MetS. Multivariate linear regression revealed that positive and negative symptoms, and to some degree waist circumference, were predictors of QoL at both time points. Our findings suggest that in the earliest stages of antipsychotic treatment, metabolic side-effects may be less influential on QoL than psychopathological severity.

Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms. We also explored the relationship between complement factors with CT, cognition and psychotic symptoms. Patients showed significantly higher levels of C1q, C4, factor B, factor H, and properdin in plasma. Among patients, higher levels of C3 in plasma were associated with worse memory recall, while higher levels of C4, factor B and factor H were associated with thinner sensory cortex. These findings link dysregulation of specific complement components to abnormal brain structure and cognition in schizophrenia.

Although schizophrenia (SZ) represents a complex multiform psychiatric disorder, one of its most striking symptoms are auditory verbal hallucinations (AVH). While the neurophysiological origin of this pervasive symptom has been extensively studied, there is so far no consensus conclusion on the neural correlates of the vulnerability to hallucinate. With a network-based fMRI approach, following the hypothesis of altered hemispheric dominance (Crow, 1997), we expected that LN alterations might result in self-other distinction impairments in SZ patients, and lead to the distressing subjective experiences of hearing voices. We used the independent component analysis of resting-state fMRI data, to first analyze LN connectivity in three groups of participants: SZ patients with and without hallucinations (AVH/D+ and AVH/D-, respectively), and a matched healthy control (HC) group. Then, we assessed the fMRI fluctuations using additional analyses based on fractional Amplitude of Low Frequency-Fluctuations (fALFF), both at the network- and region of interest (ROI)-level. Specific LN nodes were recruited in the right hemisphere (insula and Broca homologous area) for AVH/D+ , but not for HC and AVH/D-, consistent with a left hemisphere deficit in AVH patients. The fALFF analysis at the ROI level showed a negative correlation between fALFF Slow-4 and P1 Delusions PANSS subscale and a positive correlation between the fALFF Slow-5 and P3 Hallucination PANSS subscale for AVH/D+ only. These effects were not a consequence of structural differences between groups, as morphometric analysis did not evidence any group differences. Given the role of language as an emerging property resulting from the integration of many high-level cognitive processes and the underlying cortical areas, our results suggest that LN features from fMRI connectivity and fluctuations can be a marker of neurophysiological features characterizing SZ patients depending on their vulnerability to hallucinate.

Clozapine is effective at reducing symptoms of treatment-resistant schizophrenia, but it can also induce several adverse outcomes including neutropenia and agranulocytosis. We used linear mixed-effect models and structural equation modelling to determine whether pharmacokinetic and genetic variables influence absolute neutrophil count in a longitudinal UK-based sample of clozapine users not currently experiencing neutropenia (N = 811). Increased daily clozapine dose was associated with elevated neutrophil count, amounting to a 133 cells/mm³ rise per standard deviation increase in clozapine dose. One-third of the total effect of clozapine dose was mediated by plasma clozapine and norclozapine levels, which themselves demonstrated opposing, independent associations with absolute neutrophil count. Finally, CYP1A2 pharmacogenomic activity score was associated with absolute neutrophil count, supporting lower neutrophil levels in CYP1A2 poor metabolisers during clozapine use. This information may facilitate identifying at-risk patients and then introducing preventative interventions or individualised pharmacovigilance procedures to help mitigate these adverse haematological reactions.

Fall-related injury is the most common cause of functional disability and mortality in the older population. Falls in patients with schizophrenia are one of the major concerns in psychiatric hospitals. This study aimed to examine the impact of standardized operating procedures (SOP) on falls in veterans with schizophrenia. Veterans with schizophrenia were allocated to the control group (n = 345) and to the fall protection standardized operating procedures (FP-SOP) group (n = 342). Patients in the control group were given routine nursing for falls, and patients in the FP-SOP group were intervened with FP-SOP plus routine nursing. All patients were observed for one year. The study methods comply with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. We found a fall rate of 1.5% in the FP-SOP group and 4.6% in the control group, with a significant difference in the fall rate between the two groups. In addition, the difference in patient satisfaction between the two groups was statistically significant. Our findings suggest that FP-SOP is an effective strategy for fall prevention in psychiatric hospitals.

Aberrant sense of agency (SoA, a feeling of control over one's own actions and their subsequent events) has been considered key to understanding the pathology of schizophrenia. Behavioral studies have demonstrated that a bidirectional (i.e., excessive and diminished) SoA is observed in schizophrenia. Several neurophysiological and theoretical studies have suggested that aberrancy may be due to temporal delays (TDs) in sensory-motor prediction signals. Here, we examined this hypothesis via computational modeling using a recurrent neural network (RNN) expressing the sensory-motor prediction process. The proposed model successfully reproduced the behavioral features of SoA in healthy controls. In addition, simulation of delayed prediction signals reproduced the bidirectional schizophrenia-pattern SoA, whereas three control experiments (random noise addition, TDs in outputs, and TDs in inputs) demonstrated no schizophrenia-pattern SoA. These results support the TD hypothesis and provide a mechanistic understanding of the pathology underlying aberrant SoA in schizophrenia.

This study was conducted to investigate the effects of long-term low-dose lithium adjunct to antipsychotic agent use on the cognitive performance, whole-brain gray-matter volume (GMV), and interleukin-6 (IL-6) level in drug-naive patients with first-episode schizophrenia, and to examine relationships among these factors. In this double-blind randomized controlled study, 50 drug-naive patients with first-episode schizophrenia each took low-dose (250 mg/day) lithium and placebo (of the same shape and taste) adjunct to antipsychotic agents (mean, 644.70 ± 105.58 and 677.00 ± 143.33 mg/day chlorpromazine equivalent, respectively) for 24 weeks. At baseline and after treatment completion, the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive performance, 3-T magnetic resonance imaging was performed to assess structural brain alterations, and serum IL-6 levels were quantified by immunoassay. Treatment effects were assessed within and between patient groups. Relationships among cognitive performance, whole-brain GMVs, and the IL-6 level were investigated by partial correlation analysis. Relative to baseline, patients in the lithium group showed improved working memory, verbal learning, processing speed, and reasoning/problem solving after 24 weeks of treatment; those in the placebo group showed only improved working memory and verbal learning. The composite MCCB score did not differ significantly between groups. The whole-brain GMV reduction was significantly lesser in the lithium group than in the placebo group (0.46% vs. 1.03%; P < 0.001). The GMV and IL-6 reduction ratios correlated with each other in both groups (r = -0.17, P = 0.025). In the lithium group, the whole-brain GMV reduction ratio correlated with the working memory improvement ratio (r = -0.15, P = 0.030) and processing speed (r = -0.14, P = 0.036); the IL-6 reduction ratio correlated with the working memory (r = -0.21, P = 0.043) and verbal learning (r = -0.30, P = 0.031) improvement ratios. In the placebo group, the whole-brain GMV reduction ratio correlated only with the working memory improvement ratio (r = -0.24, P = 0.019); the IL-6 reduction ratio correlated with the working memory (r = -0.17, P = 0.022) and verbal learning (r = -0.15, P = 0.011) improvement ratios. Both treatments implemented in this study nearly improved the cognitive performance of patients with schizophrenia; relative to placebo, low-dose lithium had slightly greater effects on several aspects of cognition. The patterns of correlation among GMV reduction, IL-6 reduction, and cognitive performance improvement differed between groups.