Schizophrenia Bulletin Open最新文献

Objective: To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis.

Methods: 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-center study. After a baseline assessment using magnetic resonance imaging (MRI), participants were followed for at least two years to determine clinical and functional outcomes, including transition to psychosis (according to the Comprehensive Assessment of an At Risk Mental State, CAARMS), level of functioning (according to the Global Assessment of Functioning), and symptomatic remission (according to the CAARMS). GMV was measured in selected cortical and subcortical regions of interest (ROI) based on previous studies (ie orbitofrontal gyrus, cingulate gyrus, gyrus rectus, inferior temporal gyrus, parahippocampal gyrus, striatum, and hippocampus). Using voxel-based morphometry, we analysed the relationship between GMV and clinical and functional outcomes.

Results: Within the CHR sample, a poor functional outcome (GAF < 65) was associated with relatively lower GMV in the right striatum at baseline (P < .047 after Family Wise Error correction). There were no significant associations between baseline GMV and either subsequent remission or transition to psychosis.

Conclusions: In CHR individuals, lower striatal GMV was associated with a poor level of overall functioning at follow-up. This finding was not related to effects of antipsychotic or antidepressant medication. The failure to replicate previous associations between GMV and later psychosis onset, despite studying a relatively large sample, is consistent with the findings of recent large-scale multi-center studies.

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few studies have examined the intersection of stress exposure and affective distress with prediction error (PE) signals among youth at clinical high-risk (CHR). Here, 26 individuals at CHR and 19 healthy volunteers (HVs) completed a monetary incentive delay task in conjunction with fMRI. We compared these groups on the amplitudes of neural responses to surprising outcomes-PEs without respect to their valence-across the whole brain and in two regions of interest, the anterior insula and amygdala. We then examined relations of these signals to the severity of depression, anxiety, and trauma histories in the CHR group. Relative to HV, youth at CHR presented with aberrant PE-evoked activation of the temporoparietal junction and weaker deactivation of the precentral gyrus, posterior insula, and associative striatum. No between-group differences were observed in the amygdala or anterior insula. Among youth at CHR, greater trauma histories were correlated with stronger PE-evoked amygdala activation. No associations were found between affective symptoms and the neural responses to PE. Our results suggest that unvalenced PE signals may provide unique information about the neurobiology of CHR syndromes and that early adversity exposure may contribute to neurobiological heterogeneity in this group. Longitudinal studies of young people with a range of risk syndromes are needed to further disentangle the contributions of distinct aspects of salience signaling to the development of psychopathology.

Background and hypothesis: No objective tests are currently available to help diagnosis of major psychiatric disorders. This study evaluates the potential of eye movement behavior patterns to predict schizophrenia subjects compared to those with major affective disorders and control groups.

Study design: Eye movements were recorded from a training set of UK subjects with schizophrenia (SCZ; n = 120), bipolar affective disorder (BPAD; n = 141), major depressive disorder (MDD; n = 136), and healthy controls (CON; n = 142), and from a hold-out set of 133 individuals with proportional group sizes. A German cohort of SCZ (n = 60) and a Scottish cohort of CON subjects (n = 184) acted as a second semi-independent test set. All patients met DSMIV and ICD10 criteria for SCZ, BPAD, and MDD. Data from 98 eye movement features were extracted. We employed a gradient boosted (GB) decision tree multiclass classifier to develop a predictive model. We calculated the area under the curve (AUC) as the primary performance metric.

Study results: Estimates of AUC in one-versus-all comparisons were: SCZ (0.85), BPAD (0.78), MDD (0.76), and CON (0.85). Estimates on part-external validation were SCZ (0.89) and CON (0.65). In all cases, there was good specificity but only moderate sensitivity. The best individual discriminators included free viewing, fixation duration, and smooth pursuit tasks. The findings appear robust to potential confounders such as age, sex, medication, or mental state at the time of testing.

Conclusions: Eye movement patterns can discriminate schizophrenia from major mood disorders and control subjects with around 80% predictive accuracy.

Objective: Although people with schizophrenia are disproportionately affected by Hepatitis C virus (HCV) compared to the general population, HCV screening among US Medicaid recipients with schizophrenia has not been characterized. Following 1998 CDC recommendations for screening in high-risk populations, we estimated the proportion of Medicaid recipients with and without schizophrenia screened for HCV across states and over time. Examining patterns of screening will inform the current public health imperative to test all adults for HCV now that safer and more effective treatments are available.

Methods: Data are drawn from 1 353 424 Medicaid recipients aged 15-64 years with schizophrenia and frequency-matched controls from 2002 to 2012. Participants with known HCV infection one year prior and those dual-eligible for Medicare were excluded. Multivariable logistic regression estimated associations between predictor variables and HCV screening.

Results: HCV screening was low (<4%) but increased over time. Individuals with schizophrenia consistently showed higher screening compared to controls across years and states. Several demographic and clinical characteristics predicted higher screening, especially comorbid HIV (OR = 6.5; 95% CI = 6.0-7.0). Outpatient medical care utilization increased screening by nearly double in 2002 (OR = 1.8; CI = 1.7-1.9) and almost triple in 2012 (OR = 2.7; CI = 2.6-2.9).

Conclusions: Low screening was a missed opportunity to improve HCV prevention efforts and reduce liver-related mortality among people with schizophrenia. Greater COVID-19 disease severity in HCV patients and the availability of effective HCV treatments increase the urgency to improve HCV screening. Eliminating Medicaid restrictions and expanding statewide HIV policies to include HCV would have multiple public health benefits, particularly for people with schizophrenia.

Negative symptoms predict adverse outcomes within psychotic disorders, in individuals at high-risk for psychosis, and in young people in the community. There is considerable interest in the dimensional structure of negative symptoms in clinical samples, and accumulating evidence suggests a 5-factor structure. Little is known about the underlying structure of negative symptoms in young people despite the importance of this developmental stage for mental health. We used confirmatory factor analysis to test the structure of parent-reported negative symptoms at mean ages 16.32 (SD 0.68, N = 4974), 17.06 (SD 0.88, N = 1469) and 22.30 (SD 0.93, N = 5179) in a community sample. Given previously reported associations between total negative symptoms and genome-wide polygenic scores (GPS) for major depressive disorder (MDD) and schizophrenia in adolescence, we assessed associations between individual subdomains and these GPSs. A 5-factor model of flat affect, alogia, avolition, anhedonia, and asociality provided the best fit at each age and was invariant over time. The results of our linear regression analyses showed associations between MDD GPS with avolition, flat affect, anhedonia, and asociality, and between schizophrenia GPS with avolition and flat affect. We showed that a 5-factor structure of negative symptoms is present from ages 16 to 22 in the community. Avolition was most consistently associated with polygenic liability to MDD and schizophrenia, and alogia was least associated. These findings highlight the value of dissecting negative symptoms into psychometrically derived subdomains and may offer insights into early manifestation of genetic risk for MDD and schizophrenia.

Background: Schizophrenia commonly co-occurs with cardiometabolic and inflammation-related traits. It is unclear to what extent the comorbidity could be explained by shared genetic aetiology.

Methods: We used GWAS data to estimate shared genetic aetiology between schizophrenia, cardiometabolic, and inflammation-related traits: fasting insulin (FI), fasting glucose, glycated haemoglobin, glucose tolerance, type 2 diabetes (T2D), lipids, body mass index (BMI), coronary artery disease (CAD), and C-reactive protein (CRP). We examined genome-wide correlation using linkage disequilibrium score regression (LDSC); stratified by minor-allele frequency using genetic covariance analyzer (GNOVA); then refined to locus-level using heritability estimation from summary statistics (ρ-HESS). Regions with local correlation were used in hypothesis prioritization multi-trait colocalization to examine for colocalisation, implying common genetic aetiology.

Results: We found evidence for weak genome-wide negative correlation of schizophrenia with T2D (r_g = -0.07; 95% C.I., -0.03,0.12; P = .002) and BMI (r_g = -0.09; 95% C.I., -0.06, -0.12; P = 1.83 × 10^-5). We found a trend of evidence for positive genetic correlation between schizophrenia and cardiometabolic traits confined to lower-frequency variants. This was underpinned by 85 regions of locus-level correlation with evidence of opposing mechanisms. Ten loci showed strong evidence of colocalization. Four of those (rs6265 (BDNF); rs8192675 (SLC2A2); rs3800229 (FOXO3); rs17514846 (FURIN)) are implicated in brain-derived neurotrophic factor (BDNF)-related pathways.

Conclusions: LDSC may lead to downwardly-biased genetic correlation estimates between schizophrenia, cardiometabolic, and inflammation-related traits. Common genetic aetiology for these traits could be confined to lower-frequency common variants and involve opposing mechanisms. Genes related to BDNF and glucose transport amongst others may partly explain the comorbidity between schizophrenia and cardiometabolic disorders.

There is an ongoing debate about the potential risks and benefits of long-term antipsychotic treatment in schizophrenia. The data for and against the chronic use of these medicines is mostly indirect, either from observational studies potentially exposed to reverse causation bias or randomized controlled studies that do not cover beyond 2-3 years. We propose that perseverating on the question of what positive or negative outcomes are causally associated with chronic antipsychotic treatment may not lead to better answers than the limited ones that we have, given the limited feasibility of more conclusive studies. Rather, we argue that addressing the research question of the risks and benefits of antipsychotic discontinuation from a perspective of personalized medicine, can be more productive and meaningful to people living with schizophrenia. To this end, research that can quantify the risk of relapse after treatment continuation for a given individual should be prioritized. We make the case that clinically feasible neuroimaging biomarkers have demonstrated promise in related paradigms, and that could be offering a way past this long debate on the risks and benefits of chronic antipsychotic use.

Alterations to striatal reward pathways have been identified in individuals with psychosis. They are hypothesized to be a key mechanism that generate psychotic symptoms through the production of aberrant attribution of motivational salience and are proposed to result from accumulated childhood adversity and genetic risk, making the striatal system hyper-responsive to stress. However, few studies have examined whether children with psychotic-like experiences (PLEs) also exhibit these alterations, limiting our understanding of how differences in reward processing relate to hallucinations and delusional ideation in childhood. Consequently, we examined whether PLEs and PLE-related distress were associated with reward-related activation in the nucleus accumbens (NAcc). The sample consisted of children (N = 6718) from the Adolescent Brain Cognitive Development (ABCD) study aged 9-10 years who had participated in the Monetary Incentive Delay (MID) task in functional MRI. We used robust mixed-effects linear regression models to investigate the relationship between PLEs and NAcc activation during the reward anticipation and reward outcome stages of the MID task. Analyses were adjusted for gender, household income, ethnicity, depressive symptoms, movement in the scanner, pubertal development, scanner ID, subject and family ID. There was no reliable association between PLEs and alterations to anticipation- or outcome-related striatal reward processing. We discuss the implications for developmental models of psychosis and suggest a developmental delay model of how PLEs may arise at this stage of development.

Cannabis use is highly prevalent in patients with schizophrenia and worsens the course of the disorder. To understand how exposure to cannabis changes schizophrenia-related oscillatory disruptions, we investigated the impact of administering cannabis vapor containing either Δ9-tetrahydrocannabinol (THC) or balanced THC/cannabidiol (CBD) on oscillatory activity in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia. Male Sprague Dawley rats underwent lesion or sham surgeries on postnatal day 7. In adulthood, electrodes were implanted targeting the cingulate cortex (Cg), the prelimbic cortex (PrLC), the hippocampus (HIP), and the nucleus accumbens (NAc). Local field potential recordings were obtained after rats were administered either the "THC-only" cannabis vapor (8-18% THC/0% CBD) or the "Balanced THC:CBD" cannabis vapor (4-11% THC/8.5-15.5% CBD) in a cross-over design with a 2-week wash-out period between exposures. Compared to controls, NVHL rats had reduced baseline gamma power in the Cg, HIP, and NAc, and reduced HIP-Cg high-gamma coherence. THC-only vapor exposure broadly suppressed oscillatory power and coherence, even beyond the baseline reductions observed in NHVL rats. Balanced THC:CBD vapor, however, did not suppress oscillatory power and coherence, and in some instances enhanced power. For NVHL rats, THC-only vapor normalized the baseline HIP-Cg high-gamma coherence deficits. NHVL rats demonstrated a 20 ms delay in HIP theta to high-gamma phase coupling, which was not apparent in the PrLC and NAc after both exposures. In conclusion, cannabis vapor exposure has varying impacts on oscillatory activity in NVHL rats, and the relative composition of naturally occurring cannabinoids may contribute to this variability.

Introduction: People with psychotic disorders may be disproportionately affected by the traumatic effects of the COVID-19 pandemic. Childhood trauma, which also increases vulnerability to subsequent stressors, is common in individuals with psychosis. In this study, we investigated the intersection of the pandemic, childhood trauma, and psychotic and trauma-related symptoms in individuals with psychotic disorders.

Methods: We administered a cross-sectional survey to 151 participants [47 schizophrenia (SZ), 53 psychotic bipolar disorder (BP)], 51 healthy control (HC)] during the COVID-19 pandemic. Participants were asked about exposure to the pandemic's impacts, childhood trauma, and post-traumatic stress, dissociative, and psychotic symptoms.

Results: BP reported greater negative impacts to emotional health than SZ and HC and to non-COVID physical health than HC. SZ reported less impact on work and employment during the pandemic. There were no other group differences in pandemic-related adversities. We also found that cumulative exposure to the pandemic's negative impacts was significantly associated with PTSD symptoms but not psychotic or dissociative symptoms. Moreover, the number of adversities an individual experienced during the pandemic was strongly associated with the cumulative number of traumatic experiences they had in childhood.

Discussion: Our results suggest that having a psychotic disorder does not, in and of itself, increase susceptibility to the pandemic's negative impacts. Instead, we provide evidence of a graded relationship between cumulative exposure to the pandemic's negative impacts and PTSD symptom severity, as well as a graded relationship between cumulative childhood traumatic experiences and the number pandemic adversities, across diagnoses.