The role of depression in the prediction of a "late" remission in first-episode psychosis:An analysis of the OPTiMiSE study

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES). Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" re-mitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period. Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR)- 4.186, 95% confidence interval (CI)- 2.082-8.416, p < 0.001) and older age (OR- 1.081, 95% = CI 1.026-1.138, p- 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019). Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. (C) 2021 Elsevier B.V. All rights reserved

Relationships between social withdrawal and facial emotion recognition in neuropsychiatric disorders

Background: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding. Objective: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction. Methods: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task. Results: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p < .01). Social withdrawal was associated with higher accuracy in negative emotion detection, across all groups. Additionally, neuropsychiatric patients with higher social withdrawal showed lower positive emotion misclassification. Conclusions: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients’ increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

BackgroundDeficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.Materials and methodsThe initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.ResultsFEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning.ConclusionOur data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality