Schizophrenia bulletin open最新文献

Background and hypothesis: Environmental stressors may influence immune surveillance in B lymphocytes and stimulate autoimmune responses via epigenetic DNA methylation modifications in schizophrenia (SCZ).

Study design: A total of 2722, Chinese Han origin subjects were recruited in this study (2005-2011), which included a discovery follow-up cohort with 40 remitters of SCZ (RSCZ), 40 nonremitters of SCZ (NRSCZ), and 40 controls (CTL), and a replication follow-up cohort (64 RSCZ, 16 NRSCZ, and 84 CTL), as well as a case-control validation cohort (1230 SCZ and 1208 CTL). Genomic DNA methylation, target gene mRNA transcripts, and plasma autoantibody levels were measured across cohorts.

Study results: We found extensive differences in global DNA methylation profiles between RSCZ and NRSCZ groups, wherein differential methylation sites (DMS) were enriched with immune cell maturation and activation in the RSCZ group. Out of 2722 participants, the foremost DMS cg14341177 was hyper-methylated in the SCZ group and it inhibited the alternative splicing of its target gene BICD2 and may have increased its autoantigen exposure, leading to an increase in plasma anti-BICD2 IgG antibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in RSCZ endpoint samples but not in NRSCZ endpoint samples. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and positive and negative syndrome scale (PANSS) scores in the RSCZ groups, but not in the NRSCZ groups.

Conclusions: These data suggest that abnormal DNA methylation could affect autoreactive responses in SCZ, and that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.

This short introduction provides a historical and ethical overview of placebos and placebo controls in relation to schizophrenia research, with a focus on long-term clinical trials. Drawing on historical and philosophical scholarship, it sketches a two-level analysis of ethical issues that placebos and the placebo effect raise for the field, particularly in light of shifts in clinical trial methodologies and clinical practices.

Objectives: Many existing measures of prejudiced attitudes toward people with mental illness have conceptual, theoretical, and psychometric problems. The recently created Prejudice toward People with Mental Illness (PPMI) scale has addressed many of these limitations, but prejudice toward people with different mental disorders may be unique and require further exploration. This study aimed to facilitate this exploration by adapting the PPMI to focus on schizophrenia and depression, and investigate the structure, distinctiveness, and the nomological network of prejudice toward people with these mental disorders.

Study design: We adapted the original 28-item PPMI scale to create the Prejudice toward People with Schizophrenia (PPS) and Prejudice toward People with Depression (PPD) scales. There were 406 participants from the general population, who completed these scales and related measures.

Study results: The original 4-factor structure (fear/avoidance, unpredictability, authoritarianism, and malevolence) was supported for each scale. Participants expressed the highest levels of prejudice toward people with schizophrenia, followed by prejudice toward people with mental illness, and lastly by prejudice toward people with depression. Analyses supported the proposed nomological network of prejudice, which involves theoretical antecedents of social dominance orientation, right-wing authoritarianism, empathy, personality traits, disgust sensitivity, and prior contact.

Conclusions: This research provides evidence for the validity and psychometric properties of the PPMI, PPS, and PPD scales, expanding our understanding of antecedents to prejudice toward people with different mental disorders. This research also shows that we gain more insight into prejudice when we use measures targeting specific disorders rather than mental illness in general.

Research has found strong evidence for common and distinct morphometric brain abnormality profiles in nonaffective psychosis (NAff-P) and affective psychosis (Aff-P). Due to chronicity and prolonged medication exposure confounds, it is crucial to examine structural morphometry early in the course of psychosis. Using Human Connectome Project-Early Psychosis data, multivariate profile analyses were implemented to examine regional profiles for cortical thickness, cortical surface area, subcortical volume, and ventricular volume in healthy control (HC; n = 56), early illness NAff-P (n = 83), and Aff-P (n = 30) groups after accounting for normal aging. Associations with symptom severity, functioning, and cognition were also examined. Group regional profiles were significantly nonparallel and differed in level for cortical thickness (P < .001), with NAff-P having widespread cortical thinning relative to HC and Aff-P and some regions showing greater deficits than others. Significant nonparallelism of group regional profiles was also evident for cortical surface area (P < .006), with Aff-P and N-Aff-P differing from HC and from each other (P < .001). For subcortical volume, there was significant profile nonparallelism with NAff-P having an enlarged left pallidum and smaller accumbens and hippocampus (P < .028), and Aff-P having a smaller accumbens and amygdala (P < .006), relative to HC. NAff-P also had larger basal ganglia compared to Aff-P. Furthermore, NAff-P had enlarged ventricles (P < .055) compared to HC and Aff-P. Additionally, greater ventricular volume was associated with increased manic symptoms in NAff-P and Aff-P. Overall, this study found common and distinct regional morphometric profile abnormalities in early illness NAff-P and Aff-P, providing evidence for both shared and disease-specific pathophysiological processes.

Schizophrenia is marked by aberrant processing of complex speech and gesture, which may contribute functionally to its impaired social communication. To date, extant neuroscientific studies of schizophrenia have largely investigated dysfunctional speech and gesture in isolation, and no prior research has examined how the two communicative channels may interact in more natural contexts. Here, we tested if patients with schizophrenia show aberrant neural processing of semantically complex story segments, and if speech-associated gestures (co-speech gestures) might modulate this effect. In a functional MRI study, we presented to 34 participants (16 patients and 18 matched-controls) an ecologically-valid retelling of a continuous story, performed via speech and spontaneous gestures. We split the entire story into ten-word segments, and measured the semantic complexity for each segment with idea density, a linguistic measure that is commonly used clinically to evaluate aberrant language dysfunction at the semantic level. Per segment, the presence of numbers of gestures varied (n = 0, 1, +2). Our results suggest that, in comparison to controls, patients showed reduced activation for more complex segments in the bilateral middle frontal and inferior parietal regions. Importantly, this neural aberrance was normalized in segments presented with gestures. Thus, for the first time with a naturalistic multimodal stimulation paradigm, we show that gestures reduced group differences when processing a natural story, probably by facilitating the processing of semantically complex segments of the story in schizophrenia.

Economic evaluations of lifestyle interventions for people with mental illness are needed to inform policymakers and managers about implementing such interventions and corresponding reforms in routine mental healthcare. We aimed to evaluate changes in healthcare costs 18 months after the implementation of a multidisciplinary lifestyle-enhancing treatment for inpatients with severe mental illness (MULTI) versus treatment as usual (TAU). In a cohort study (n = 114; 65 MULTI, 49 TAU), we retrospectively retrieved cost data in Euros on all patient sessions, ward stay, medication use, and hospital referrals in the quarter year at the start of MULTI (Q1 2014) and after its evaluation (Q3 2015). We used linear regression analyses correcting for baseline values and differences between groups, calculated deterministic incremental cost-effectiveness ratios for previously shown changes in physical activity, metabolic health, psychosocial functioning, and additionally quality of life, and performed probabilistic sensitivity analyses including cost-effectiveness planes. Adjusted regression showed reduced total costs per patient per quarter year in favor of MULTI (B = -736.30, 95%CI: -2145.2 to 672.6). Corresponding probabilistic sensitivity analyses accounting for uncertainty surrounding the parameters showed statistically non-significant cost savings against health improvements for all health-related outcomes in MULTI compared to TAU. It is concluded that MULTI did not increase healthcare costs while improving health outcomes. This indicates that starting lifestyle interventions does not need to be hampered by costs. Potential societal and economic value may justify investment to support implementation and maintenance. Further research is needed to study this hypothesis.

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved ("caught up") to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.