Schizophrenia (Heidelberg, Germany)最新文献

Recent research has examined the effectiveness of transcranial direct current stimulation (tDCS) as an adjunctive treatment for antipsychotics, finding mixed results on cognitive, positive, and negative symptoms. We tested if individuals with psychosis have reduced electric field strength compared to healthy controls and assessed the potential causal factors. We hypothesized that either cortical thinning due to the disorder or increased scalp thickness due to secondary effects of the disorder were causal factors. Using the Psychosis Human Connectome Project dataset, we simulated electric field models for 136 individuals with psychosis, 73 first-degree relatives, and 43 healthy controls. We compared group differences of electric field strength at bilateral dorsolateral prefrontal cortex (dlPFC), targeted with two montages (Fp1-Fp2 & F3-Fp2) commonly used to treat cognitive impairment. We additionally compared groups on scalp, skull, and cerebrospinal fluid thickness at bilateral dlPFC and the three electrode locations. Mediation analyses assessed if tissue thickness and BMI were causal factors for group differences while controlling for age and sex. Individuals with psychosis had lower electric field strength for bilateral dlPFC for both montages. Scalp thickness was also greater for individuals with psychosis, but cerebrospinal fluid thickness was not significantly different. BMI was a significant mediator for the group difference seen in both scalp thickness and electric field strength. Future treatment studies using tDCS in the psychosis population should include electric field modeling to assess its effectiveness given the increased risk of obesity. Individualized montages based on head models may also improve effectiveness.

Patients with schizophrenia with early onset age have been shown to exhibit more severe negative symptoms. Genetic, biomarker, postmortem brain, and imaging studies indicate the involvement of immune abnormalities in the pathophysiology of schizophrenia. In this study, we examined the moderating role of early onset on the associations between clinical symptoms and neutrophil-to-lymphocyte ratio (NLR) in medication-naïve first-episode schizophrenia (MNFES). A total of 97 MNFES patients were recruited. Neutrophil (NEU), LYM, and NLR values were compared between early-onset (EO) and non-early-onset (non-EO) patients with schizophrenia to explore the potential influence of EO on the correlations between NLR and symptoms. The results showed no differences in NEU and NLR values between the EO and non-EO groups. In the EO group, NEU and NLR values significantly correlated with general psychopathology and total score (all p < 0.05), whereas lymphocyte counts were not correlated with symptoms of schizophrenia. NEU and NLR were not associated with symptoms in the non-EO group. Linear regression analysis in the EO group revealed that NEU or NLR values were a predictive biomarker for the clinical symptoms. Our study indicates that EO patients had greater severe negative symptoms compared with non-EO patients. In addition, onset age mediates the relationships of NEU and NLR values with clinical symptoms, suggesting that an immune disturbance, particularly increased innate immune response in EO patients, may be involved in the psychophysiology of schizophrenia.

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

Nonverbal communication habitually leaks out in ways that expose underlying thoughts, true feelings, and integrity of a counterpart. Social cognition is deficient in a wide range of mental disorders, including schizophrenia (SZ). Inferring social signals through the eyes is pivotal for social interaction but remains poorly investigated. The present work aims to fill this gap by examining whether and, if so, how reading language of the eyes is altered in SZ. We focused on male SZ, primarily because the disorder manifests a gender-specific profile. Patients and matched typically developing (TD) individuals were administered the Reading the Mind in the Eyes Test-Modified (RMET-M) and Emotions in Masked Faces (EMF) task that provide comparable visual information. The findings indicate that in SZ, the emotion recognition profile is similar to TD, with a more accurate recognition of some emotions such as fear, neutral expressions, and happiness than the others (sadness and disgust). In SZ, however, this profile is shifted down: all emotions are recognized less accurately than in TD. On the RMET-M, patients are also less precise, albeit they perform better on items with positive valence. In SZ only, recognition accuracy on both tasks is tightly linked to each other. The outcome reveals global challenges for males with SZ in inferring social information in the eyes and calls for remediation programs to shape social cognition. This work offers novel insights into the profiles of social cognitive deficits in mental disorders that differ in their gender prevalence.

Psychosis progresses along a continuum. While heterogeneity is evident across the continuum, it remains unknown whether this is also reflected in white matter (WM) heterogeneity and whether parsing WM heterogeneity may reveal subgroups with more pronounced clinical features. This analysis included 212 participants consisting of healthy controls (HC, n = 59), individuals with high schizotypy (SPT, n = 27), at-risk mental state (ARMS, n = 35), and patients with first episode psychosis (FEP, n = 50) and schizophrenia (SZ, n = 41). Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI), and fibre density (FD), a non-tensor-derived diffusion marker, was computed. The Person-Based-Similarity Index (PBSI) and Coefficient of Variation Ratio (CVR) were computed to assess global and local heterogeneity. ANOVAs were performed to determine whether people with deviating PBSIs exhibit more pronounced clinical features. Global heterogeneity for all diffusion parameters significantly differed across groups, with greatest difference in heterogeneity between SZ and HC. Results further indicate that FA deviators exhibit lower global functioning and higher negative symptoms. Local FA heterogeneity was greater in FEP relative to ARMS and HC in almost all WM tracts, while SZ patients specifically showed greater heterogeneity in the right thalamic radiation and the left uncinate compared to HCs. Group differences in WM heterogeneity might be indicative of symptom specificity and duration. While these findings offer valuable insights into the neurobiological variability of psychosis, they are primarily hypothesis-generating. Future large-scale studies are warranted to test the robustness of diffusion markers and their clinical relevance.

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.