Schizophrenia (Heidelberg, Germany)最新文献

Individuals with schizophrenia face significantly higher mortality rates than the general population, with a typical reduction in life expectancy of 15-20 years. This study investigated 10-year all-cause mortality and its clinical correlates in a Romanian cohort of patients with schizophrenia, using real-world clinical and hospital and forensic records. A total of 635 individuals hospitalized between 2010 and 2013 were followed for 10 years. Mortality rates, causes of death, and risk factors were assessed using Cox regression models and standardized mortality ratios (SMRs). During the follow-up, 123 patients (19.37%) died, corresponding to a mortality rate of 21.3 per 1000 person-years. The SMR was 1.58 compared to the Romanian general population. Non-violent causes predominated, with cardiovascular disease (27.64%) and infections (17.07%) being the most frequent. Violent deaths, including suicides and accidents, accounted for 17.07% of all mortality. The mean age at death was 58.97 years, reflecting a 17-year reduction in life expectancy. Age was the strongest independent predictor of mortality (HR = 1.07, p < 0.001). Use of second-generation antipsychotics (HR = 0.37, p < 0.001) and low frequency hospitalization (HR = 0.09, p < 0.001) were significantly associated with reduced all-cause and cause-specific mortality. Schizophrenia is associated with significantly increased premature mortality, primarily due to preventable physical illnesses and violent deaths. Early intervention, sustained treatment adherence, and integrated medical care are essential to improve survival outcomes.

Psychiatric disorders present a significant global health burden with limited effective medications. Observing the widespread comorbidities between diabetes and psychiatric disorders, we explored the potential of repurposing antidiabetic drug targets for psychiatric treatments. We identified 32 target genes of 60 antidiabetics and performed Mendelian randomization analyses using expression and protein quantitative trait loci data from brain tissues alongside summary data for seven psychiatric disorders. Additionally, we conducted colocalization analyses, replication analyses in blood and at the single-cell level, single-cell gene annotation, developmental trajectory analysis, and various functional assessments. We found that elevated GANC expression in the putamen basal ganglia, nucleus accumbens basal ganglia, cortex, and whole blood was associated with a reduced risk of bipolar disorder (OR, 0.532-0.877; P, 4.04 × 10^-5 to 1.45 × 10^-7), implying that antagonism of GANC by the antidiabetic drug miglitol could increase bipolar risk. Conversely, increased ABCC8 expression in the cortex, cerebellum, cerebellar hemisphere, and VIP- and LAMP5-expressing inhibitory neurons was linked to a higher risk of schizophrenia (OR, 1.054-1.119; P, 1.46 × 10^-3 to 4.42 × 10^-5), suggesting that ABCC8 inhibition by sulfonylureas or glinides may lower the risk of schizophrenia. Colocalization analysis further confirmed the above associations. GANC and ABCC8 displayed specific developmental trajectories, and functional analyses revealed that they affected psychiatric risk through pathways related to potassium ion channels, insulin secretion, and glucose metabolism. Our findings highlight GANC and ABCC8 as potential targets, suggesting caution in miglitol use for bipolar disorder and the potential repurposing of sulfonylureas and glinides for schizophrenia.

Perinatal insults (e.g., obstetric complications, substance exposure) are increasing in prevalence and confer risk for psychotic-like experiences in offspring, contributing to a growing public health burden. Perinatal insults often co-occur, creating methodological challenges in understanding their impacts on psychosis-spectrum phenotypes. Data-driven approaches to organizing perinatal insults and testing their longitudinal effects on psychotic-like experiences in youth increases ecological validity and translational utility. Using data from 11,417 youth ages 9-14 across five years of the Adolescent Brain Cognitive Development (ABCD) Study, data-driven dimensions of perinatal insults were derived through exploratory factor analysis of thirty-one perinatal insults. Latent growth modeling tested the effect of perinatal insult dimensions on trajectories (baseline, rate-of-change, year-four severity) of distressing psychotic-like experiences. Six dimensions of perinatal insults were observed (substance exposure, obstetric complications, birth complications, postnatal challenges, parental age, medical needs). Substance exposure (β = 0.42, 95% CI [0.20, 0.63]), obstetric complications (β = 0.34, 95% CI [0.08, 0.61]), and parental age (β = 1.00, 95% CI [0.76, 1.22]) were associated with elevated baseline psychotic-like experiences. Perinatal insult dimensions were not associated with increasing rates-of-change in psychotic-like experiences. Medical needs (β = -0.12, 95% CI [-0.20, -0.05]) and parental age (β = -0.11, 95% CI [-0.18, -0.03]) were associated with steeper declines in psychotic-like experiences. Perinatal insult dimensions remained associated with elevated psychotic-like experiences at year-four. Data-driven dimensions of perinatal insults are associated with stably elevated psychotic-like experience trajectories across early adolescence. Given the role of psychotic-like experiences in later psychopathology and functioning, early identification of at-risk offspring is critical in reducing the public health burden of these exposures.

Treatment resistance affects up to one in four individuals with psychosis in the first few years of illness. However, there is limited information about the brain changes associated with treatment resistance, restricting our ability to develop effective prognostic biomarkers or new treatments. Using resting-state functional MRI, we examined striatocortical connectivity in 87 patients who presented a non-affective first-episode of psychosis and 118 healthy controls, with follow-up imaging on more than half of the participants in the next 6 years, totaling 361 images. Crucially, we identified 30 patients who presented treatment-resistant psychosis in this follow-up period. Thus, we examined baseline (at first episode) and longitudinal striatocortical differences within psychosis subgroups (treatment-responsive and treatment-resistant psychosis), and between patients subgroups and healthy controls. Compared to healthy controls, participants with treatment-responsive psychosis presented baseline differences in functional connectivity of ventral striatal systems, without changes over time; whereas patients with treatment-resistant psychosis showed both baseline and longitudinal differences in ventral striatal systems, compared to healthy controls. Treatment-responsive and treatment-resistant psychosis groups differed in longitudinal changes in connectivity between ventral striatal and temporal cortical regions. This is one of the circuits which has been previously related to symptom improvements in patients with first-episode of psychosis. No baseline differences were observed between the two psychosis groups. Overall, treatment-resistant psychosis is characterized by longitudinal changes in striatal systems in early psychosis, which might be used as the basis of future prognostic biomarkers.

Structural and functional brain abnormalities in schizophrenia (SZ) are well-documented, yet the role of the glymphatic system remains largely unexplored. Given emerging evidence linking the microbiome-gut-brain axis to SZ, this study aims to investigate the glymphatic system function in SZ patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its associations with gut microbiota and cognitive performance. Multi-omics data were obtained from a cohort of 87 SZ patients and 70 healthy controls (HCs), including fecal 16S rRNA sequencing, DTI-ALPS index analysis, and cognitive assessments. Correlation and mediation analyses were conducted to explore the relationships among the gut microbiome, DTI-ALPS index, and cognitive performance. Compared to HCs, patients with SZ exhibited significantly lower DTI-ALPS indices in the left, right, and bilateral hemispheres. These indices were positively associated with multiple cognitive domains. In addition, gut microbial dysbiosis was observed in SZ, characterized by a decrease in butyrate-producing bacteria and an increase in pathogenic bacteria. Exploratory analyses further revealed a tripartite link among the key microbial genera, DTI-ALPS indices, and cognitive performance. Notably, the higher abundance of Proteus as well as the lower abundance of Blautia and Faecalibacterium may contribute to poorer cognitive performance, potentially through disruptions in the right DTI-ALPS index. These findings provide novel insights into glymphatic dysfunction in SZ and highlight a potential microbiota-glymphatic-cognition pathway contributing to cognitive impairments.

Faces are essential for effective communication and social interaction. Substantial alterations in face processing are observed in a wide range of mental disorders, in particular, in schizophrenia (SZ). Individuals with SZ experience difficulties to seeing faces in face-pareidolia images that easily elicit face impression in their typically developing (TD) peers. Here, males with SZ and TD controls performed a task with Arcimboldo-like Face-n-Food face-pareidolia images during MEG recording. The outcome reveals that already at early processing stages, the bursts of gamma oscillations differ between SZ and TD individuals in terms of frequency and topography. When contrasting gamma activity for face responses between TD individuals and SZ, the maximum activation for the frequency range of 40-45 Hz originates from the right LOC. In accord with this, in SZ, an advanced analysis of brain connectivity unfolding over time in the low (40-45 Hz) and high (65-70 Hz) gamma ranges reveals alterations in communication between the right LOC and the social brain. In SZ, early engagement of the right LOC is limited to transmitting signals to higher-order regions, whereas in TD, it also serves as a recipient of sophisticated feedback communication from the higher-order areas of the social brain. This study offers novel insights into altered brain communication and the origins of social cognition deficits in SZ that is characterized by a skewed sex ratio with substantial gender differences in disease manifestation.

Schizophrenia is a complex neuropsychiatric disorder, and the abnormalities in brain networks during its early stages remain incompletely understood. Previously, we identified a stable high-intensity functional network, termed the "Frame Network," in healthy individuals and observed its aberrations in schizophrenia patients. This study aimed to utilize this network to explore disconnection abnormalities in early-stage schizophrenia. This study compared drug-naïve first-episode schizophrenia patients (FES, n = 83), ultra-high risk of schizophrenia (UHR, n = 65), and matched healthy controls (HC, n = 67). Frame networks were analyzed across groups, and differences were assessed using networks from healthy people (HP) derived from stable connections in two public datasets. Network-Based Statistics (NBS)-predict identified connections for a disease classification model. FES patients were divided into two subtypes, and connections related to negative symptoms were identified using Connectome-based Predictive Modeling (CPM). UHR and FES patients showed increasing abnormalities in frame connections compared to controls. HP and FES frame networks effectively differentiated groups. Connections crucial for classification were found in the prefrontal motor cortex. Patients divided into two subtypes showed distinct pathological presentations. Frame networks predicted negative symptoms effectively. Variations in regions such as the visual and prefrontal cortex were observed based on symptom severity, indicating diverse underlying connection differences in the clinical heterogeneity of schizophrenia. Our findings indicate that Frame Network abnormalities likely play a significant role in early-stage pathological processes of schizophrenia and show promise as biomarkers for disease classification and symptom prognosis.

Previous studies on metabolic profiling have shown decreased plasma levels of betaine in schizophrenia. Betaine serves as a substrate of betaine-homocysteine methyltransferase, which converts homocysteine to methionine. A decrease in betaine may lead to the elevation of homocysteine and an insufficient supply of methyl donors, which may affect DNA methylation. To explore how decreased betaine levels could affect brain structural changes often observed in schizophrenia, the present study investigated the relationships in 27 patients with chronic schizophrenia and 49 healthy comparison individuals. We found that the effects of betaine on brain volume are group-specific, and significant correlations between betaine and notable brain areas implicated in schizophrenia's pathophysiology including the superior temporal gyrus. These findings suggest that betaine levels may contribute to aberrant structural changes in schizophrenia.

In healthy individuals, active hand-movements typically elicit earlier neural processing than passive one, reflected by more positive contrast estimates of the first-order temporal derivative (TD) of hemodynamic response function (HRF) in functional MRI (fMRI) analyses. This temporal advantage might be due to prior movement-awareness and predictive mechanisms that support self-other distinction. However, it is unknown whether impaired predictive mechanisms in Schizophrenia Spectrum Disorder (SSD) influence earlier neural processing. Patients with SSD (n = 20) and healthy controls (HC; n = 20) performed active and passive hand movements, while detected delays in video feedback of their own or another person's hand. The recorded fMRI data were analysed applying TD to examine timing and second-order dispersion derivative (DD) to evaluate duration of neural responses. Compared to HC, patients with SSD exhibited delayed BOLD responses during active vs. passive movements in the right caudate nucleus, lobule VIII of right cerebellar hemisphere, left superior temporal gyrus, left postcentral gyrus, left thalamus, and left putamen/insula. Furthermore, during active movement with own hand feedback, patients with SSD showed delayed activation in the bilateral putamen and insula. Delayed insula/putamen responses' were associated with symptom severity. However, these exploratory findings remain not significant after correction for multiple comparisons and attenuated with Spearman's-rank correlations. Delayed BOLD responses in patients with SSD, particularly in the right cerebellar lobule VIII, left thalamus, and bilateral insula/putamen may contribute to disturbances in the sense of agency. Altered timing/duration of neural responses reflects new insight underlying deficits in predictive and feedback-monitoring mechanisms in SSD.

Schizophrenia (SZ) is a complex disorder characterized by positive and negative symptoms that have been linked to dysfunction in cognition and reward motivation. Recent findings show higher inter-subject variability in SZ in various cognitive functions. This raises the question of whether there is also higher intra-subject variability in SZ at the psychological level, specifically increased variability across the trials of a psychological task within the subject itself, that is, intra-subject variability. To examine fluctuations in behavior during a reward-based discrimination and liking task, we analyzed intra-subject variability in SZ and observed the following: (i) increased intra-subjective variability across all four behavioral measures, that is, response times (RT) for discrimination and liking tasks, as well as accuracy (ACC) and liking ratings; (ii) significant correlation of the different measures' intra-subject variabilities across the distinct tasks, e.g., RT, ACC, and liking ratings among each other; and (iii) relation of the increased intra-subjective variability in the behavioral measures (RT, ACC, liking) with overall and general psychopathological symptom severity, as measured by the positive and negative syndrome scale (PANSS). Together, we demonstrate abnormally increased intra-subjective variability in a reward-motivation task in SZ and its key role in relation to symptom severity. This increased intra-subject variability at the psychological-behavioral level suggests abnormal and imprecise timing in cognitive processing, which aligns with analogous findings of temporal imprecision at the neural level.