Longitudinal course of core cognitive domains in first-episode acute and transient psychotic disorders compared with schizophrenia.

Acute and transient psychotic disorder (ATPD) is characterized by acute onset of psychotic symptoms and early recovery. Contrastingly, schizophrenia (SZ) is a chronic mental disorder characterized by impaired functioning including a deficit in cognition. In SZ, the cognitive deficit is among the core symptoms, but in ATPDs, the existing evidence brings mixed results. Our primary aim was to compare three core cognitive domains (executive functioning/abstraction, speed of processing and working memory) of patients diagnosed with ATPD and SZ over a 12-month period. Moreover, we explored how these diagnostic subgroups differed in their clinical characteristics. We recruited 39 patients with a diagnosis of SZ and 31 with ATPD with schizophrenic symptoms. All patients completed clinical and neuropsychological assessments. At baseline, we used a one-way ANCOVA model with a group as the between-subjects factor. Mixed-model repeated-measures ANOVAs with time as the within-subjects factor and group as the between-subjects factor were run to test the overtime differences. At baseline, we did not find any differences in cognition - with sex, education and age as covariates - between ATPDs and SZ. After one year, all patients showed an improvement in all three domains, however, there were no significant overtime changes between ATPDs and SZ. Regarding clinical profiles, ATPDs demonstrated less severe psychopathology and better functioning compared to SZ both at baseline and after 12 months. The medication dosage differed at retest, but not at baseline between the groups. Our findings suggest clinical differences and a similar trajectory of cognitive performance between these diagnostic subgroups.

MHC II-EGFP Knock-in Mouse Model.

The MHC II-EGFP knock-in mouse model enables us to visualize and track MHC-II-expressing cells in vivo by expressing enhanced green fluorescent protein (EGFP) fused to the MHC class II molecule under the MHC II beta chain promoter. Using this model, we can easily identify MHC-II-expressing cells, including dendritic cells, B cells, macrophages, and ILC3s, which play a key role as antigen-presenting cells (APCs) for CD4+ T cells. In addition, we can also precisely identify and analyze APC-containing tissues and organs. Even after fixation, EGFP retains its fluorescence, so this model is suitable for immunofluorescence studies, facilitating an unbiased characterization of the histological context, especially with techniques such as light-sheet fluorescence microscopy. Furthermore, the MHC II-EGFP knock-in mouse model is valuable for studying the molecular mechanisms of MHC II gene regulation and expression by making it possible to correlate MHC II expression (MHC II-EGFP) with surface fraction through antibody detection, thereby shedding light on the intricate regulation of MHC II expression. Overall, this model is an essential asset for quantitative and systems immunological research, providing insights into immune cell dynamics and localization, with a tool for precise cell identification and with the ability to study MHC II gene regulation, thus furthering the understanding of immune responses and underlying mechanisms © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Characterization of antigen-specific MHC II loading compartment tubulation toward the immunological synapse Basic Protocol 2: Characterization of overall versus surface MHC II expression Basic Protocol 3: Identification and preparation of the lymphoid organs Basic Protocol 4: Quantification of APC content in lymphoid organs by fluorescence stereomicroscopy Basic Protocol 5: Quantification and measurement of intestinal lymphoid tissue by light-sheet fluorescence stereomicroscopy Basic Protocol 6: Visualization of corneal APCs Basic Protocol 7: Quantification of MHC II+ cells in maternal milk by flow cytometry Support Protocol 1: Cell surface staining and flow cytometry analysis of spleen mononuclear cells.

Inflammation and cognitive performance in first-episode schizophrenia spectrum disorders: The moderating effects of childhood trauma.

In this study, we aimed to determine whether childhood trauma moderated the relationship between inflammation and cognitive functioning in persons with first-episode schizophrenia spectrum disorders (SSDs). We included data from 92 individuals who participated in the nationwide Early-Stage Schizophrenia Outcome study. These individuals completed the Childhood Trauma Questionnaire, provided a fasting blood sample for high-sensitivity C-reactive protein analysis, and underwent extensive neuropsychological testing. The intervening effects of age, sex, education, smoking status, and body mass index were controlled. Results indicated that childhood trauma levels significantly moderated the relationship between inflammation and four cognitive domains: speed of processing, working memory, visual memory, and verbal memory. Inflammation also predicted verbal memory scores irrespective of childhood trauma levels or the covariates. Upon further exploration, the significant moderation effects appeared to be primarily driven by males. In conclusion, a history of childhood trauma may be an important determinant in evaluating how inflammation relates to the cognitive performance of people with first-episode SSDs, particularly in speed of processing, working memory, visual memory, and verbal memory. We recommend that future researchers examining the effect of inflammation on cognitive functioning in SSDs include trauma as a moderating variable in their models and further examine additional moderating effects of sex.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Cognitive flexibility in schizophrenia: A confirmatory factor analysis of neuropsychological measures.

Cognitive flexibility (CF) is the ability to adapt cognitive strategies according to the changing environment. The deficit in CF has often been linked to various neurological and psychiatric disorders including schizophrenia. However, the operationalization and assessment of CF have not been unified and the current research suggests that the available instruments measure different aspects of CF. The main objective of the present study was to compare three frequently used neuropsychological measures of CF-Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Color and Word Test (SCWT) in a population of patients (N = 220) with first-episode schizophrenia spectrum disorders in order to evaluate their convergent validity. The hypothesis of an underlying latent construct was tested via a confirmatory factor analysis. We used a one-factor CF model with scores from WCST, SCWT and TMT as observed variables. The established model showed a good fit to the data (χ2 = 1.67, p = 0.43, SRMR = 0.02, RMSEA = 0.0, CFI = 1.00). The highest factor loading was found in WCST as CF explained most of the variance in this neuropsychological measure compared to the other instruments. On the other hand, a TMT ratio index and a SCWT interference demonstrated lowest loadings in the model. The findings suggest that not all the frequently used measures share an underlying factor of CF or may capture different aspects of this construct.

Smoking and attention in schizophrenia spectrum disorders: What are we neglecting?

Introduction: Individuals with schizophrenia spectrum disorders (SSDs) record elevated rates of smoking, which is often attributed to their effort to self-medicate cognitive and attentional symptoms of their illness. Empirical evidence for this hypothesis is conflicting, however. In this study, we aimed to test predictions derived from the cognitive self-medication hypothesis. We predicted that cigarette smoking status and extent would predict the attentional performance of participants with SSDs. Simultaneously, we wished to address methodological gaps in previous research. We measured distinct attentional components and made adjustments for the effects of other, attention-modulation variables. Methods: Sixty-one smokers (82.0% males, 26.73 ± 6.05 years) and 61 non-smokers (50.8% males, 27.10 ± 7.90 years) with recent-onset SSDs completed an X-type Continuous Performance Test, which was used to derive impulsivity and inattention component scores. Relationships between the two component scores and cigarette smoking status and extent were assessed using hierarchical regression. Effects of estimated premorbid intellectual functioning and antipsychotic medication dosage were held constant. Results: Smokers had significantly higher inattention component scores than non-smokers when covariates were controlled (p = 0.026). Impulsivity remained unaffected by smoking status (p = 0.971). Cigarette smoking extent, i.e., the number of cigarettes smoked per day, was not associated with either inattention (p = 0.414) or impulsivity (p = 0.079). Conclusion: Models of smoking-related attentional changes can benefit from the inclusion of sample-specific component scores and attention-modulating covariates. Under these conditions, smokers with SSDs can show a partial attentional benefit. However, the limited scope of this benefit suggests that the cognitive self-medication hypothesis requires further testing or reconsidering.

MHC II - EGFP knock-in mouse model is a suitable tool for systems and quantitative immunology.

Immunology is a rapidly evolving field of research with sophisticated models and methods. However, detailed data on total immune cell counts and population distributions remain surprisingly scarce. Nevertheless, recently established quantitative approaches could help us understand the overall complexity of the immune system. Here, we studied a major histocompatibility complexclass II - enhanced green fluorescent protein knock-in mouse model to precisely identify and manipulate lymphoid structures. By combining flow cytometry with light sheet microscopy, we quantified MHC II+ populations of the small intestine and associated individual mesenteric lymph nodes, with 36.7 × 106 cells in lamina propria, 3.0 × 105 cells in scattered lymphoid tissue and 1.1 × 106 cells in Peyer's patches. In addition to these whole-organ cell counts, we assessed approximately 1 × 106 total villi in the small intestine and 450 scattered lymphoid tissue follicles. By direct noninvasive microscopic observation of a naturally fully translucent mouse organ, the cornea, we quantified 12 ± 4 and 35 ± 7 cells/mm2 Langerhans- and macrophage-like populations, respectively. Ultimately, our findings show that flow cytometry with quantitative imaging data analysis enables us to avoid methodological discrepancies while gaining new insights into the relevance of organ-specific quantitative approaches for immunology.

The relationships between cognitive reserve, cognitive functioning and quality of life in first-episode schizophrenia spectrum disorders.

Cognitive reserve (CR) has been conceptualized as an individual's ability to optimize or maximize performance through differential recruitment of brain networks. As such, CR may contribute to the heterogeneity of cognitive deficits observed in schizophrenia. This study aimed to assess the relationships between CR, cognition and quality of life in first-episode (FES) patients. A total of 137 patients with either ICD-10 schizophrenia or "acute and transient psychotic disorders" diagnosis, and 62 healthy controls had completed a comprehensive assessment of six cognitive domains: speed of processing, attention, working memory/flexibility, verbal memory, visual memory, and abstraction/executive functioning. CR was calculated from the participants' education, premorbid IQ, and socioeconomic status. The results suggested that in patients, CR was positively related to cognitive performance in all domains, explaining 42.6% of the variance observed in cognition overall. Effects of CR in the control group were limited to three domains: speed of processing, abstraction/executive function and working memory/flexibility. These results suggest that CR largely contributes to cognitive variations present in FES patients. In addition, CR was negatively related to the social construct of patients' quality of life, and positively to symptom severity and general functioning.