Association between the COVID-19 pandemic and psychiatric symptoms in people with preexisting obsessive-compulsive, eating, anxiety, and mood disorders: a systematic review and meta-analysis of before-after studies.

AIM: To determine whether the coronavirus disease 2019 (COVID-19) pandemic was associated with a change in psychiatric symptoms in people with preexisting obsessive-compulsive, eating, anxiety, and mood disorders compared to their prepandemic levels. METHODS: We searched MEDLINE, CINAHL, PsycINFO, and Embase from inception until February 16, 2022. Studies were included if they reported prepandemic and during-pandemic psychiatric symptoms, using validated scales, in people with preexisting mood, anxiety, eating, or obsessive-compulsive disorders. Two reviewers independently screened studies, extracted data, and assessed evidence certainty. Random-effects meta-analyses were conducted. Effect sizes were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Eighteen studies from 10 countries were included. Of the 4465 included participants, 68% were female and the average age was 43 years. Mood and obsessive-compulsive disorders were the most studied disorders. During-pandemic psychiatric measurements were usually collected during nationwide lockdown. Obsessive-compulsive symptoms worsened among people with obsessive-compulsive and related disorders, with a moderate effect size (N = 474 [six studies], SMD = -0.45 [95% CI, -0.82 to -0.08], I2 = 83%; very low certainty). We found a small association between the COVID-19 pandemic and reduced anxiety symptoms in people with mood, anxiety, obsessive-compulsive, and eating disorders (N = 3738 [six studies], SMD = 0.11 [95% CI, 0.02-0.19], I2 = 63%; very low certainty). No change in loneliness, depressive, or problematic eating symptoms was found. CONCLUSION: People with obsessive-compulsive and related disorders may benefit from additional monitoring during the COVID-19 pandemic and possibly future pandemics. Other psychiatric symptoms were stable in people with the specific disorders studied. Overall, evidence certainty was very low.

The complement system in schizophrenia: where are we now and what's next?

The complement system is a set of immune proteins involved in first-line defense against pathogens and removal of waste materials. Recent evidence has implicated the complement cascade in diseases involving the central nervous system, including schizophrenia. Here, we provide an up-to-date narrative review and critique of the literature on the relationship between schizophrenia and complement gene polymorphisms, gene expression, protein concentration, and pathway activity. A literature search identified 23 new studies since the first review on this topic in 2008. Overall complement pathway activity appears to be elevated in schizophrenia. Recent studies have identified complement component 4 (C4) and CUB and Sushi Multiple Domains 1 (CSMD1) as potential genetic markers of schizophrenia. In particular, there is some evidence of higher rates of C4B/C4S deficiency, reduced peripheral C4B concentration, and elevated brain C4A mRNA expression in schizophrenia patients compared to controls. To better elucidate the additive effects of multiple complement genotypes, we also conducted gene- and gene-set analysis through MAGMA which supported the role of Human Leukocyte Antigen class (HLA) III genes and, to a lesser extent, CSMD1 in schizophrenia; however, the HLA-schizophrenia association was likely driven by the C4 gene. Lastly, we identified several limitations of the literature on the complement system and schizophrenia, including: small sample sizes, inconsistent methodologies, limited measurements of neural concentrations of complement proteins, little exploration of the link between complement and schizophrenia phenotype, and lack of studies exploring schizophrenia treatment response. Overall, recent findings highlight complement components-in particular, C4 and CSMD1-as potential novel drug targets in schizophrenia. Given the growing availability of complement-targeted therapies, future clinical studies evaluating their efficacy in schizophrenia hold the potential to accelerate treatment advances.

Analysis of the complement component C4 gene with schizophrenia subphenotypes.

BACKGROUND: The complement component C4 gene has been identified as a strong marker for schizophrenia (SCZ) risk. The C4 gene has a complex genetic structure consisting of variable structural elements (C4A, C4B, C4L, and C4S) and compound structural forms (C4AL, C4BL, C4AS and C4BS). In addition, the variations in C4 structural forms may have a direct or indirect effect on the brain expression level of C4A and C4B proteins. Previous studies have associated C4AL with higher brain C4A expression and sex-dimorphism of C4 between males and females was observed. STUDY DESIGN: A total of 613 patients with DSM-IV SCZ or schizoaffective disorder (SCZ-AFF) were recruited to investigate the relationship between C4 gene variants and clinical characteristics of SCZ (age of onset, symptom severity, and global assessment of functioning (GAF)). This study also explored the effect of sex on the association of C4 with SCZ. 434 patients were included in the final analyses after genetic quality control. RESULTS: We observed associations between C4 and clinical characteristics of SCZ (age of onset, symptom severity, GAF) and found significant differences when males and females were examined separately. CONCLUSION: Overall, our preliminary findings encourage future investigations of C4 in SCZ-related phenotypes, including antipsychotic response and side effects. The study sample was of moderate size; therefore, further studies in larger samples are needed to extend and validate these results.

Children and Youth Who Use Cannabis for Pain Relief: Benefits, Risks, and Perceptions.

We provide up-to-date perspectives on the benefits and risks of medical cannabis for pain management in children and youth. To date, only two studies (a case report and a small observational study) have examined the effects of medical cannabis on pain in children and youth. No controlled trial has commented on long-term safety of medical cannabis. Findings from the recreational cannabis literature reveal significant potential short- and long-term risks of regular cannabis use, including impaired driving, depression, suicidality, psychosis, and tolerance. Despite this, many children and youth are self-medicating with cannabis, and perceive regular cannabis use to be safe. There is a need for better education and counselling of patients regarding the benefits and risks of medical cannabis use.