Schizophrenia (Heidelberg, Germany)最新文献

The P3b is a prominent event-related potential (ERP) with maximal amplitude between 250 ms and 500 ms after the onset of a rare target stimulus within a sequence of standard non-target stimuli (oddball paradigm). Several studies found reduced P3b amplitudes in patients with schizophrenia compared to neurotypicals. Our work and the literature suggest that temporal imprecision may play a large pathophysiological role in schizophrenia. Here, we investigated whether reduced P3b amplitudes result from reduced neural activity (power) or temporal imprecision (inter-trial phase coherence; ITC) in delta and theta bands, using two EEG datasets from different studies with different oddball paradigms (Study 1: 19 patients with schizophrenia and 17 matched controls, Study 2: 26 patients and 26 controls). Both studies revealed typical P3b ERP components with smaller amplitudes in patients. Reduced ITC in patients was found in the delta band, which correlated with P3b peak amplitudes for all participant groups (ρ = 0.58-0.89). In Study 1, we also found significant differences between patients and controls in ITC in the theta band, which also correlated with P3b peak amplitudes (patients' ρ = 0.64, controls' ρ = 0.54). This was not found in Study 2. The results indicate that P3b amplitude reduction in patients with schizophrenia is linked to a reduction in temporal precision of neural activity. These results expand the notion of imprecision in temporal processing at phenomenological, psychological, and neurological levels that have been related to disturbances of the sense of self. They confirm that temporal imprecision may be more important than the reduction of neural activity itself.

This study assessed plasma levels of essential amino acids (EAA) in drug-naïve first episode psychosis (FEP) patients at diagnosis and after 10 weeks of antipsychotic treatment. Forty FEP patients were enrolled at baseline, with blood samples collected before and after a 10-week antipsychotic treatment period. Plasma EAA levels were measured using an LC/MS/MS method. Psychotic symptoms were evaluated using standardized inventories before and after treatment. A decrease in BPRS score of more than 40% was used to indicate treatment response. Thirty-five healthy volunteers served as the control group. Baseline plasma levels of Thr, Met, Leu, Lys, His, and Tyr were higher in FEP patients than in healthy controls. After 10 weeks of treatment, Leu, His, and Tyr increased further, primarily in treatment-responsive patients. Conversely, Val level was lower than controls in patients at baseline and remained unchanged after treatment. Increased EAA levels were correlated with lower (less severe) scores in positive symptom scales. Treatment non-responders had persistently low Tyr/large neutral amino acid (LNAA) ratio. Tyr/LNAA ratio increased after treatment, specifically in treatment-responders. Phe/Tyr ratio decreased post-treatment in both responder and non-responder groups. Elevated EAA levels in FEP patients may signify compensatory responses to increased physiological demand for neurotransmitters or energy. Combining specific EAA supplementation with antipsychotic treatment may enhance treatment response in these patients.

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, -9.9; 95% confidence interval, -12.4, -7.3; p < 0.0001; Cohen's d effect size, 0.65). PANSS subscale and Clinical Global Impression-Severity scores also improved significantly with xanomeline/trospium versus placebo. Subgroup analyses consistently favored xanomeline/trospium over placebo regardless of differences in participant age, sex, race, body mass index, and baseline PANSS total score. These results add to existing evidence demonstrating robust and reliable improvements in symptoms with xanomeline/trospium across a broad spectrum of people with schizophrenia.

This study investigated the relative associations of psychosis proneness symptom domains with habitual interpersonal emotion regulation (IER) use in a sample of young adults (n = 420, age 18-29). Multiple regression models showed that attenuated negative symptoms were related to using less, while attenuated positive symptoms and depression were related to using more IER. These findings suggest symptom-specific IER patterns across different symptom dimensions of psychosis proneness.

Deviations in syntax production have been well documented in schizophrenia spectrum disorders (SSD). Recently, we have shown evidence for transdiagnostic subtypes of syntactic complexity and diversity. However, there is a lack of studies exploring brain structural correlates of syntax across diagnoses. We assessed syntactic complexity and diversity of oral language production using four Thematic Apperception Test pictures in a sample of N = 87 subjects (n = 24 major depressive disorder (MDD), n = 30 SSD patients both diagnosed according to DSM-IV-TR, and n = 33 healthy controls (HC)). General linear models were used to investigate the association of syntax with gray matter volume (GMV), fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD). Age, sex, total intracranial volume, group, interaction of group and syntax were covariates of no interest. Syntactic diversity was positively correlated with the GMV of the right medial pre- and postcentral gyri and with the FA of the left superior-longitudinal fasciculus (temporal part). Conversely, the AD of the left cingulum bundle and the forceps minor were negatively correlated with syntactic diversity. The AD of the right inferior-longitudinal fasciculus was positively correlated with syntactic complexity. Negative associations were observed between syntactic complexity and the FA of the left cingulum bundle, the right superior-longitudinal fasciculus, and the AD of the forceps minor and the left uncinate fasciculus. Our study showed brain structural correlates of syntactic complexity and diversity across diagnoses and HC. This contributes to a comprehensive understanding of the interplay between linguistic and neural substrates in syntax production in psychiatric disorders and HC.

The increasing availability of biobanks is changing the way individuals are identified for genomic research. This study assesses the validity of a self-reported clinical diagnosis of schizophrenia. The study included 1744 clinically-ascertained participants with schizophrenia or schizoaffective disorder depressed-type (SA-D) diagnosed by self-report and/or research interview and 1453 UK Biobank participants with self-reported and/or medical record diagnosis of schizophrenia or SA-D. Unaffected controls included a total of 501,837 participants. We assessed the positive predictive values (PPV) of self-reported clinical diagnoses against research interview and medical record diagnoses. Polygenic risk scores (PRS) and phenotypes relating to demographics, education and employment were compared across diagnostic groups. The variance explained (r²) in schizophrenia PRS for each diagnostic group was compared to samples in the Psychiatric Genomics Consortium (PGC). In the clinically-ascertained participants, the PPV of self-reported schizophrenia for a research diagnosis of schizophrenia was 0.70, which increased to 0.81 after expanding the research diagnosis to schizophrenia or SA-D. In UK Biobank, the PPV of self-reported schizophrenia for a medical record diagnosis was 0.74. Compared to participants who self-reported, participants with a clinically-ascertained research diagnosis were younger and more likely to have a high school qualification. Participants with a medical record diagnosis in UK Biobank were less likely to be employed or have a high school qualification than those who self-reported. Schizophrenia PRS did not differ between participants that had a diagnosis from self-report, research diagnosis or medical records. Polygenic liability r², for all diagnosis definitions, fell within the distribution of PGC schizophrenia cohorts. Self-reported measures of schizophrenia are justified in genomic research to maximise sample size and reduce the burden of in-depth interviews on participants, although within sample validation of diagnoses is recommended.

Structuring sensory events in time is essential for interacting with the environment and producing adaptive behaviors. Over the past years, the microstructure of temporality received increasing attention, recognized as a fundamental factor influencing cognitive, affective, and social abilities, whose alteration can underlie the etiopathogeneses of some clinical symptoms in psychiatric disorders. The present research investigated multisensory temporal processing in individuals with schizophrenia (N = 21), bipolar disorder (N = 20) and healthy controls (N = 21) in order to explore a plausible link between multisensory alterations in the temporal order of events and the psychopathological dimensions underlying psychosis. We asked participants to temporally order audio-tactile, visual-tactile, and audio-visual stimuli, and we administered different psychopathological scales to explore depressive, manic and psychotic symptoms. Results demonstrated that both subjects with schizophrenia and bipolar disorder are less precise in temporal order judgment independently of the sensory modalities involved. Interestingly, reduced precision in temporal processing of patients is positively associated with the presence and severity of positive symptoms. Our findings support the hypothesis that low-level sensory alterations in temporal structure may contribute to the emergence of clinical symptoms such as delusions, hallucinations, and disorganized behaviors.

Intervention for social cognition could be key to improving social functioning in patients with schizophrenia. A first step towards its clinical implementation involves interviewing patients about their subjective difficulties with social cognition as they experience them in the real world. The present study focused on the clinical subtypes classified by the discrepancies between the subjective difficulties in social cognition and actual cognitive impairment. A total of 131 outpatients with schizophrenia and 68 healthy controls were included. Objective measurement of social cognition was performed using a test battery covering four representative domains, and subjective difficulties were determined by a questionnaire covering the same domains. A two-step cluster analysis explored the potential classification of social cognition in patients with schizophrenia. There was little correlation between the objective performance on social cognition tasks and subjective difficulties in social cognition. The analysis yielded three clusters: the low-impact group (low objective impairment and low subjective difficulties), the unaware group (high objective impairment but low subjective difficulties), and the perceptive group (moderate objective impairment and high subjective difficulties). Positive, negative, and general symptoms were more severe in the two groups that showed impaired performance on the social cognition tasks (i.e., the unaware and perceptive groups) than those in the low-impact group. Neurocognition and functional capacity were the lowest in the unaware group, and social functioning was the lowest in the perceptive group. Awareness about the clinical subtypes of social cognition could serve as a guidepost for providing individualized, targeted interventions.

Schizophrenia is a complex neuro-psychiatric disorder including positive symptoms, negative symptoms, and cognitive deficits. A key cognitive dysfunction in schizophrenia is a deficit in visual working memory (VWM). VWM involves three distinct stages: encoding, maintenance, and retrieval. The deficit in any one stage would produce the same symptom (i.e., poor VWM), although their causes are not the same. In this study, we used a retro-cue VWM task that provides helpful cues at different stages: early in maintenance (early cue), late in maintenance (late cue), or during retrieval (retrieval cue). This modification would help "tag" or identify the cognitive stage(s) most responsible for impaired VWM performance in schizophrenia. Additionally, we took advantage of this tagging feature and applied 6 Hz transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex (DLPFC) and right posterior parietal cortex (PPC)-which has previously been shown to enhance VWM in low-performing healthy individuals-to examine whether tACS would improve a specific stage or all stages of VWM processing in schizophrenia. We observed that cues significantly enhanced performance in low-performing patients, who benefited equally from early and late maintenance cues, but not from retrieval cues. These low-performers also responded well to theta tACS in their overall VWM performance as opposed to a specific VWM stage. No improvement effect was observed in high-performing patients for both retro cue and tACS. Together, our data suggest that 1) low-performing patients' VWM deficits likely stem from poor memory consolidation rather than retrieval, 2) right frontoparietal theta tACS can improve low-performing patients' VWM performance, and 3) such facilitatory tACS effect is not selective of a specific VWM stage and thus is likely driven by an improvement in overall visual attention.