Schizophrenia (Heidelberg, Germany)最新文献

Recent studies have showed aberrant connectivity of cerebello-thalamo-cortical circuit (CTCC) in schizophrenia (SCZ), which might be a heritable trait. However, these individual studies vary greatly in their methods and findings, and important areas within CTCC and related genetic mechanism are unclear. We searched for consistent regions of circuit dysfunction using a functional magnetic resonance imaging (fMRI) meta-analysis, followed by meta-regression and functional annotation analysis. Gene annotation analysis was performed to identify genes over-expressed in these regions by using the Allen Human Brain Atlas, followed by a set of gene functional feature analyses. 19 studies (1333 patients and 1174 healthy controls) were included in this meta-analysis. SCZ was characterized by hyperconnectivity of the auditory network, visual system, and sensorimotor areas, and hypoconnectivity of the frontal gyrus, cerebellum, thalamus, and caudate nucleus, which were significantly linked to age, sex, duration of illness, and the severity of symptoms and functionally enriched in domains involving self, sensory, action, and social. 2922 genes were significantly over-expressed in these regions, which were enriched for important molecular functions, biological processes, and cellular components of the neurons/cells in the brain as well as SCZ and other mental diseases. These genes were specially expressed in the brain tissue, in the neurons of the cerebellum, subcortex and cortex and during nearly all developmental stages, and constructed a protein-protein interaction network supported by 85 hub genes with functional significance. These findings suggest key regions aberrantly connected within CTCC in SCZ, which may indicate the neural substrate of "cognitive dysmetria" and be a consequence of complex interactions from a wide range of genes with diverse functional features.

Facial stimuli are relevant social cues for humans and essential signals for adequate social interaction. Impairments in face processing are well-documented in schizophrenia and linked to symptomatology, yet the underlying neural dynamics remain unclear. Here, we investigated the processing and underlying neural temporal dynamics of task-irrelevant emotional face stimuli using combined EEG/fMRI in 14 individuals with schizophrenia and 14 matched healthy controls. Specifically, fMRI-informed region-of-interests were subjected to EEG-Dynamic Causal Modeling (DCM) analyses. Among six fMRI-informed EEG-DCM models, alterations in effective connectivity emerged between the primary visual cortex (V1) and the left occipital fusiform gyrus (lOFG). Specifically, individuals with schizophrenia showed enhanced backward connectivity from the lOFG to V1 for stimuli preceded by fearful (but not happy or neutral) faces. Connectivity strength was strongly correlated with self-reported difficulties in comprehending, processing, or articulating emotions (as assessed by the Toronto Alexithymia Scale-20) in individuals with schizophrenia but not in healthy controls. Enhanced backward connectivity from the lOFG to V1 potentially indicates heightened attention towards fearful surroundings and a propensity to assign salience to these stimuli in individuals with schizophrenia. The link to TAS-20 scores indicates that this neural deficit has real-world implications for how individuals with schizophrenia perceive and relate to their emotions and the external world, potentially contributing to the social and cognitive difficulties observed in the disorder.

The aim of this study was to assess mortality risk in people with schizophrenia in Lithuania from 2001 and 2020. Cause-specific and all-cause mortality risk among patients with schizophrenia was assessed using a retrospective cohort study design. The cohort identified all patients with schizophrenia diagnosis (ICD-10 code F20) who were admitted to the Vilnius Republican Psychiatric Hospital from 1 January, 2001 to December 31, 2020. Dates of death and emigration were obtained from the Central Population Register. The standardized mortality ratios (SMRs) were calculated by dividing the observed number of deaths among patients with schizophrenia by the expected number of deaths, calculated using the national rates. The final cohort included 7883 patients, with 2458 observed deaths. An increased all-cause mortality risk was found for both sexes (SMR = 1.96; 95% CI 1.88-2.04) compared to the general population. The most common cause-specific mortality risk was found for diseases of the circulatory system (SMR = 2.17; 95% CI 2.05-2.30). Other significant increases in cause-specific mortality risk were observed for infectious diseases, mental and behavioural disorders, diseases of the nervous system and respiratory system, diseases of the genitourinary system, as well as external causes. Patients with schizophrenia do not benefit from the health strategies that have led to reduced mortality in the general population. To close the mortality gap, smoking and alcohol cessation interventions, cardiovascular and cancer screening and monitoring, early diagnosis, and interventions for identified physical diseases should be regarded as imperative.

In West Africa, the long-term consequences of poor early psychosis recovery include poverty, neglect, and community ostracization. To understand the potential for digital health approaches to support early psychosis care in Ghana, we conducted a survey study among early psychosis patients and their caregivers about mental health needs, technology use and access, and interest in digital mental health. Hospital staff at Accra Psychiatric Hospital reviewed hospital medical records from January 2023 - December 2023 identifying young adults (≥18 years old) who had experienced psychosis symptoms for the first time within the prior five years. Trained data assessors contacted these individuals via telephone and invited them and their caregivers to participate; those providing informed consent were interviewed via phone in Twi or English. Overall, 256 individuals participated in the survey, including 121 young adults experiencing early psychosis and 135 caregivers of early psychosis patients. The majority (80%) of early psychosis patients and their caregivers expressed interest in digital mental health for early psychosis and had access to a mobile phone (91%) and necessary mobile infrastructure. Early psychosis patients were most interested in information about managing stress and improving mood via a digital resource (72%). Caregivers desired a digital tool to provide information about psychosis symptoms (86%). Our study among those experiencing early psychosis and their caregivers in Ghana suggests readiness and acceptability of digital mental health for early psychosis care.

The neural mechanisms underlying the association between childhood trauma (CT) and psychosis spectrum disorders remains unclear. The objective of this study is to examine the relationship between childhood trauma and functional connectivity of fronto-limbic regions in a large sample of antipsychotic-naïve patients with first episode psychosis (FEP). Resting state fMRI data from 105 FEP patients and 123 healthy controls (HC) were used. Our regions of interest included bilateral hippocampus/amygdala and ventromedial prefrontal cortex (vmPFC). Childhood Trauma Questionnaire (CTQ) total and subscale scores were correlated with the resting state functional connectivity (rsFC) data. Partial correlation analyses indicated that higher CTQ sexual abuse subscale scores in FEP patients were associated with increased left amygdala-vmPFC rsFC (r(59) = 0.27, p < 0.05) and higher CTQ emotional neglect subscale scores in FEP patients were associated with increased left hippocampus-vmPFC rsFC (r(59) = 0.26, p < 0.05). Follow-up analysis showed a significant interaction effect of group (FEP and HC) and CTQ score (sexual abuse subscale) on left amygdala-vmPFC rsFC (β = 0.014, p < 0.05). Higher CTQ sexual abuse subscale scores were associated with increased rsFC in FEP patients (β = 0.56, p < 0.001). but reduced rsFC in healthy controls (β = -0.56, p < 0.001). The results also provide support for the long-term differential impact of trauma subtypes on the human brain. Overall, the results contribute to the understanding of the neural mechanisms underlying the association between childhood trauma and psychosis spectrum disorders.

Oxidative stress (OS) is crucial in schizophrenia (SCZ) pathology. Ferroptosis, a recently discovered cell death pathway linked to OS, might contribute to the development of SCZ. This study investigated the association between ferroptosis markers and cognitive impairments in chronic SCZ patients. A retrospective analysis was conducted on 204 chronic SCZ patients with cognitive deficits and 216 healthy controls (HC) matched for relevant characteristics. Plasma levels of ferroptosis and OS markers, including iron, ferritin (FE), transferrin (TF), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), glutathione (GSH), sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured. Standardized assessments like the positive and negative syndrome scale (PANSS), and Montreal Cognitive Assessment (MoCA) were used to evaluate psychiatric symptoms, and cognitive function. SCZ patients showed significant differences in markers compared to the HC group (P < 0.01). Multiple linear regression analysis revealed that decreased GSH and iron levels, along with elevated SOD levels, were significantly associated with the overall severity of psychiatric symptoms. Additionally, reduced GPX4 levels and increased ACSL4 and FE levels were significantly linked to negative symptoms and cognitive impairments. Notably, GPX4 emerged as a key predictor for cognitive function in abstraction and language domains. Our study revealed alterations in the altered plasma levels of GPX4, GSH, iron, ACSL4, FE, and SOD in chronic SCZ patients, which might indicate a close association between biomarkers of ferroptosis and OS and the psychiatric symptoms and cognitive deficits observed in these individuals.

Impaired insight into illness occurs in up to 98% of patients with schizophrenia, depending on the stage of illness, and leads to negative clinical outcomes. Previous neuroimaging studies suggest that impaired insight in patients with schizophrenia may be related to structural and functional anomalies in frontoparietal brain regions. To date, limited studies have investigated the association between regional cerebral blood flow (CBF) and impaired insight in schizophrenia. Therefore, we sought to investigate the relationship between regional CBF, as measured by arterial spin labeling (ASL), and impaired insight in participants with schizophrenia. A total of 32 participants were included in the analysis. Impaired insight in patients with schizophrenia was measured using the VAGUS, Self-report (VAGUS-SR). Resting-state regional CBF was measured using pseudo-continuous ASL (pCASL) and extracted using SPM12 and REX toolbox. Whole brain analysis found that impaired insight was associated with higher regional CBF in the right angular gyrus, left supramarginal gyrus, and right superior frontal region when controlling for age, gender, smoking status, and illness severity. The results indicate that impaired insight in schizophrenia is related to regional CBF in frontoparietal areas. These neuroimaging findings can serve as therapeutic targets for intervention, such as with non-invasive brain stimulation.

The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.

Schizophrenia (SZ), schizoaffective disorder (SZA), bipolar disorder (BD), and psychotic depression (PD) are associated with premature death due to preventable general medical comorbidities (GMCs). The interaction between psychosis, risk factors, and GMCs is complex and should be elucidated. More research particularly among those with SZA or PD is warranted. We evaluated the association between registry-based psychotic disorders and GMC diagnoses in a large national sample of participants with different psychotic disorders. In addition, we examined whether body mass index (BMI) and smoking as risk factors for GMCs explain differences between diagnostic groups. This was a cross-sectional study of a clinical population of participants (n = 10,417) in the Finnish SUPER study. Registry-based diagnoses of psychotic disorders and hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cancers, ischemic heart disease, and liver disorders were obtained. Participants' BMI and self-reported smoking were recorded. Total effect of diagnostic category adjusted for age and sex as well as direct effect including known risk factors was calculated using logistic regression. Regardless of diagnostic category, participants had high BMI (average 30.3 kg/m²), and current smoking was common (42.4%). Diabetes and COPD were more common in SZ than in other diagnostic categories. The differences between psychotic disorders were not explained by obesity or smoking status only. Obesity and smoking were prevalent in all diagnostic categories of psychotic disorders, and continued efforts at prevention are warranted. Additional differences in GMC prevalence exist between psychotic disorders that are not explained by obesity and smoking.

Numerous brain imaging studies have reported white matter alterations in schizophrenia, but the lipidome analysis of the corresponding tissue remains incomplete. In this study, we investigated the lipidome composition of six subcortical white matter regions corresponding to major axonal tracks in both control subjects and schizophrenia patients. All six regions exhibited a consistent pattern of quantitative lipidome alterations in schizophrenia, involving myelin-forming and mitochondria associated lipid classes. While alteration levels of myelin-forming lipids, particularly sphingolipids, aligned with the extent of the myelin changes reported in structural brain imaging studies, a significant decrease of mitochondria in the white matter, indicated by the lipidome alterations, was not previously investigated. To verify this effect, we performed lipidome analysis in a larger set of individuals and in the mitochondria-enriched membrane fraction, as well as directly quantified mitochondrial content. Our results suggest a substantial reduction of the mitochondrial quotient accompanied by the imbalance in myelin lipids in schizophrenia white matter.