Schizophrenia (Heidelberg, Germany)最新文献

Clozapine is highly effective for treatment-resistant schizophrenia but is underutilized due to patient and clinician-related concerns. Little is known about the general level of patient satisfaction with clozapine and determinants thereof. We therefore explored determinants of patient satisfaction with clozapine in individuals diagnosed with schizophrenia spectrum disorders (SSDs). Cross-sectional data from 480 clozapine users were used to examine demographic and clinical factors, including symptom severity, treatment response, and adverse drug reactions (ADRs). Patient satisfaction was self-rated on a scale of 1 to 10. Results showed a mean satisfaction score of 7.4 (SD = 1.9), with significant associations between satisfaction and treatment response (B = 0.42, R² = 0.19, p = 3.9 × 10⁻¹⁸), symptom severity (B = 0.10, R² = 0.05, p = 2.06 × 10^-9), occurrence of ADRs (B = -0.16, R² = 0.06, p = 3.2 × 10^-5), and recreational drug use (B = -1.32, R² = 0.05, p = 2.09 × 10^-4). Hypersalivation and prolonged sleep duration were the only ADRs linked to lower satisfaction (B = -0.72, R² = 0.06, p = 3.5 × 10^-5 and B = -0.57, R² = 0.04, p = 1.4 × 10^-3, respectively). Despite concerns about ADRs, treatment effectiveness showed a stronger association with patient satisfaction among clozapine users than the occurrence of ADRs. In conclusion, our findings suggest that strategies aimed at bolstering clozapine's effectiveness may help counter worldwide underprescription rates of clozapine in patients with SSDs.

Machine learning has been proposed to utilize D-amino acid oxidase (DAO) and DAO activator (DAOA [or pLG72]) protein levels to ascertain disease status in schizophrenia. However, it remains unclear whether machine learning can effectively evaluate clinical features in relation to DAO and DAOA in schizophrenia patients. We employed an interpretable machine learning (IML) framework including linear regression, least absolute shrinkage and selection operator (Lasso) models, and generalized additive models (GAMs) to analyze DAO/DAOA levels using 380 Taiwanese schizophrenia patients. Additionally, we incorporated 27 parameters encompassing demographic variables, clinical assessments, functional outcomes, and cognitive function as features. The IML framework facilitated linear and non-linear relationships between features and DAO/DAOA. DAO levels demonstrated significant associations with the 17-item Hamilton Depression Rating Scale (HAMD17) based on linear regression. The Lasso model identified four features-HAMD17, age, working memory, and overall cognitive function (OCF)-and highlighted HAMD17 as the most significant feature, using DAO from chronically stable patients. Utilizing DAOA from acutely exacerbated patients, the Lasso model also identified four features-OCF, Scale for the Assessment of Negative Symptoms 20-item, quality of life scale (QLS), and category fluency-and emphasized OCF as the most significant feature. Furthermore, GAMs revealed a non-linear relationship between category fluency and DAO in chronically stable patients, as well as between QLS and DAOA in acutely exacerbated patients. The study suggests that an IML framework holds promise for assessing linear and non-linear relationships between DAO/DAOA and various features in clinical assessments, functional outcomes, and cognitive function in patients with schizophrenia.

This study aimed to assess the independent and joint associations of genomic and exposomic liabilities for schizophrenia with distressing psychotic experiences (PEs) and their persistence in early adolescence. The Adolescent Brain and Cognitive Development Study data from children with European ancestry were used (N = 5122). The primary outcome was past-month distressing PEs at the 3-year follow-up. Secondary outcomes were distressing PEs at varying cutoffs of persistence. Multilevel logistic regression models were used to test the associations of binary modes (>75th percentile) of polygenic risk score for schizophrenia (PRS-SCZ₇₅) and exposome score for schizophrenia (ES-SCZ₇₅) on the outcomes. Relative excess risk due to interaction (RERI) calculation indicated additive interaction. When analyzed independently, PRS-SCZ₇₅ was not significantly associated with past-month distressing PEs but with lifetime (OR 1.29 [95% CI 1.08, 1.53]) and repeating distressing PEs ≥2 waves (OR 1.34 [95% CI 1.08, 1.65]); whereas, ES-SCZ₇₅ was consistently associated with all outcomes, with increasing strength of association as a function of PEs persistence (one wave: OR 2.77 [95% CI 2.31, 3.31]; two waves: OR 3.16 [95% CI 2.54, 3.93]; three waves: OR 3.93 [95% CI 2.86, 5.40]; four waves: OR 3.65 [95% CI 2.34, 5.70]). When considered jointly, ES-SCZ₇₅ and PRS-SCZ₇₅ did not additively interact to predict past-month distressing PEs but showed significant additive interactions for lifetime (RERI = 1.26 [95%CI 0.14, 2.38]) and repeating distressing PEs ≥2 waves (RERI = 1.79 [95%CI 0.35, 3.23]). Genomic and exposomic liabilities for schizophrenia were independently and jointly associated with distressing PEs and their persistence in early adolescence.

Social cognition, the perception and processing of social information, is adversely affected in multiple psychiatric, neurological, and neurodevelopmental disorders, and these impairments negatively impact quality of life for individuals across the globe. Despite the clear importance of social cognition, efforts to advance research via harmonization of data across cultures and diagnoses has been stymied by the lack of uniformly used and suitable assessments. To address this issue, the current study conducted an expert survey and consensus process to identify social cognitive assessments that are best suited for cross-cultural and transdiagnostic use among adults. A large group of experts in social cognition were surveyed to gather nominations for cross-culturally and transdiagnostically appropriate measures. These measures were then critically evaluated by a smaller group of experts using a Delphi consensus process to identify the best existing tasks for each use. Ninety-eight experts, representing 25 countries, responded to the initial survey and nominated a total of 81 tasks. Initial rounds of the Delphi process identified 50 tasks with adequate psychometric properties that were then subdivided into social cognition domains. For each domain, members ranked the five best tasks, once for cross-cultural use and once for transdiagnostic use, and rated the suitability of those tasks for the intended use. No tasks were identified as ideally suited for either use; however, within each domain, 4-5 tasks emerged as the most consistently selected, and all were ranked as having "good" or better suitability for use. While there is still a critical need for social cognitive assessments that are specifically designed for cross-cultural and transdiagnostic use, there does appear to be a handful of existing tasks that are currently available and likely informative. Caution is warranted however, as these still require comprehensive evaluation in cross-cultural and transdiagnostic studies.

The complex relationship between frailty and schizophrenia has yet to be fully understood. This study aims to clarify their relationship by investigating their genetic links. We hypothesize a shared genetic architecture and a bidirectional causal relationship between the two conditions. Utilizing summary genetic data from European genome-wide association studies, we analyzed genetic associations through global and local correlations, shared genomic loci, tissue enrichments, and functional genes. Bidirectional Mendelian Randomization (MR) was employed to infer causality. Our findings show a positive genetic correlation between frailty and schizophrenia (LDSC: r_g = 0.117, p = 6.686 × 10^-7; HDL: r_g = 0.101, p = 5.63 × 10^-13) and local correlations in three genomic regions (chr9: 94167203-96671698, p = 2.21 × 10^-6; chr11: 112459488-114257728, p = 1.01 × 10^-5; and chr18: 77149991-78017158, p = 9.57 × 10^-6). We identified 111 genomic loci associated with both conditions and demonstrated that genetic variants for frailty and schizophrenia share tissue enrichments and functional genes in brain. MR analysis suggests that frailty increases the likelihood of schizophrenia (OR: 1.763, 95% CI: 1.259-2.468, p = 0.001) and vice versa (β: 0.012, 95% CI: 0.006-0.018, p < 0.001). Our research supports the presence of a shared genetic basis and bidirectional causality between frailty and schizophrenia. These findings necessitate further investigation in diverse populations to confirm and expand on this genetic understanding.

Adverse childhood experiences (ACEs) are common in people at clinical high-risk for psychosis (CHR), however, the relationship between ACEs and long-term clinical outcomes is still unclear. This study examined associations between ACEs and clinical outcomes in CHR individuals. 344 CHR individuals and 67 healthy controls (HC) were assessed using the Childhood Trauma Questionnaire (CTQ), the Bullying Questionnaire and the Childhood Experience of Care and Abuse (CECA). CHR were followed up for up to 5 years. Remission from the CHR state, transition to psychosis (both defined with the Comprehensive Assessment of an At Risk Mental State), and level of functioning (assessed with the Global Assessment of Functioning) were assessed. Stepwise and multilevel logistic regression models were used to investigate the relationship between ACEs and outcomes. ACEs were significantly more prevalent in CHR individuals than in HC. Within the CHR cohort, physical abuse was associated with a reduced likelihood of remission (OR = 3.64, p = 0.025). Separation from a parent was linked to an increased likelihood of both remission (OR = 0.32, p = 0.011) and higher level of functioning (OR = 1.77, p = 0.040). Death of a parent (OR = 1.87, p = 0.037) was associated with an increased risk of transitioning to psychosis. Physical abuse and death of a parent are related to adverse long-term outcomes in CHR. The counter-intuitive association between separation from a parent and outcomes may reflect the removal of a child from an adverse environment. Future studies should investigate whether interventions targeting the effect of specific ACEs might help to improve outcomes in this population.

Cardiovascular diseases (CVDs) are the leading cause of premature mortality in patients with schizophrenia spectrum disorders (SSDs). However, the detailed categorization of these conditions remains insufficiently explored. This study aims to identify CVDs comorbidity patterns among inpatients with SSDs and to investigate associated factors. Electronic medical records (EMRs) data from three neuropsychiatric hospitals (2015-2023) in China was conducted. Comorbidity patterns were revealed through latent class analysis (LCA), and multinomial logit analysis were utilized to evaluate the effect of factors on these patterns, calculating odds ratios (ORs) and 95% confidence intervals (CIs). Among the 2830 inpatients with SSD, four distinct comorbidity patterns were identified based on their dominant characteristics: low-risk CVDs (47.86%), primary hypertension (30.15%), heart failure (12.99%), and cardiac valve and vascular disorders (8.99%). Compared to the low-risk CVD group, male patients demonstrated a higher probability of primary hypertension (OR = 1.15) and heart failure (OR = 5.36). Significant associations were observed between comorbid CVDs and the use of typical antipsychotics, atypical antipsychotics, anxiolytics and sedatives, antidepressants, and mood stabilizers. Notably, perphenazine (OR = 22.06) and chlorpromazine hydrochloride (OR = 7.09) were strongly linked to comorbid heart failure. Among Chinese patients with SSDs, four distinct CVD comorbidity patterns were identified, with hypertension and heart failure displaying strong specificity. Variations in demographic characteristics and psychotropic medication use provide valuable insights for treatment and management.

Altered neural excitation/inhibition (E/I) balance has long been suspected as a potential underlying cause for clinical symptoms in schizophrenia (SZ). Recent methodological advancements linking the spectral slope (β) of neurophysiological recordings - such as them electroencephalogram (EEG) - to E/I ratio provided much-needed tools to better understand this plausible relationship. Importantly, most approaches treat E/I ratio as a stationary feature in a single scaling range. On the other hand, previous research indicates that this property might change over time, as well as it can express different characteristics in low- and high-frequency regimes. In line, in this study we analyzed resting-state EEG recordings from 30 patients with SZ and 31 healthy controls (HC) and characterized E/I ratio via β separately for low- (1-4 Hz) and high- (20-45 Hz) frequency regimes in a time-resolved manner. Results from this analysis confirmed the bimodal nature of power spectra in both HC and SZ, with steeper spectral slopes in the high- compared to low-frequency ranges. We did not observe any between-group differences in stationary (i.e., time-averaged) neural signatures, however, the temporal variance of β in the 20-45 Hz regime was significantly reduced in SZ patients when compared to HC, predominantly over regions corresponding to the dorsal attention network. Furthermore, this alteration was found correlated to positive clinical symptom scores. Our study indicates that altered E/I ratio dynamics are a characteristic trait of SZ that reflect pathophysiological processes involving the parietal and occipital cortices, potentially responsible for some of the clinical features of the disorder.

Schizophrenia is a complex developmental disorder whose molecular mechanisms are not fully understood. The developmental course of schizophrenia can be modeled with human induced pluripotent stem cell (hiPSC) -derived brain cells that carry patient-specific genetic risk factors for the disorder. Although transcriptomic characterization of the patient-derived cells is a standard procedure, microRNA (miRNA) profiling is less frequently performed. To investigate the role of miRNAs in transcriptomic regulation in schizophrenia, we performed miRNA sequencing for hiPSC-derived neurons from five monozygotic twin pairs discordant for schizophrenia and six controls (CTR). We compared the miRNA expression to differentially expressed genes (DEGs) reported for the same cells in our earlier work. We found 21 DEmiRNAs between the affected twins (AT) and CTR with implications for the regulation of neuronal function. In addition, a separate analysis of three AT with treatment-resistant schizophrenia (TRS), their unaffected twins (UT), and CTR revealed an upregulation of four miRNAs in the UT compared to both AT and CTR. The DEmiRNAs found between the UT and CTR were associated with increased cAMP/PKA signaling and synaptogenesis signaling in the UT. We hypothesize that the upregulation of these processes in the UT could be linked to compensatory features against schizophrenia.

This study tested whether intersensory attention deficits in people with schizophrenia (SZ) relate to aberrant ongoing oscillations in sensory cortices. Electroencephalography (EEG) was recorded while individuals with schizophrenia (N = 27) and healthy controls (HC; N = 27) performed a visual-tactile target detection task. Ongoing alpha (8-12 Hz) and lower beta (13-20 Hz) band oscillations in visual and sensorimotor cortices were examined. Behavioral data suggested an intersensory attention deficit in patients. EEG data revealed stronger alpha-band oscillations for tactile vs. visual attention conditions in the visual cortex of both study groups. In the sensorimotor cortex contralateral to the tactile stimulation site, patients showed an additional intersensory attention effect in ongoing beta-band oscillations, which was negatively related to cognitive and positive symptoms of the PANSS. Our findings extend previous results from unisensory attention research and suggest that deficits in intersensory attention and alterations in sensorimotor beta oscillations are related to schizophrenia symptomatology.