Despite mixed findings, increasing evidence suggests that people with first-episode psychosis (FEP) show increased pro-inflammatory and pro-oxidative status. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to conduct a systematic literature search of cross-sectional studies comparing in vivo inflammatory and oxidative blood markers between FEP patients and healthy controls. We analyzed 61 independent samples from 59 publications, including 3002 patients with FEP (ie, patients with FEP, early psychosis, first-episode schizophrenia or early schizophrenia) and 2806 controls. After controlling for multiple comparisons, our meta-analysis showed that total antioxidant status and docosahexaenoic acid levels were significantly lower in FEP patients than in controls, whereas levels of homocysteine, interleukin-6 and tumor necrosis factor alpha were significantly higher in FEP patients than in controls. This suggests that FEP patients had reduced antioxidant status and a pro-inflammatory imbalance, and that these biological processes may be targets for managing FEP.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n=35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p adj =6.73x10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

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Background There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. Methods We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. Results We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. Limitations Most of the studies were inadequately powered (sample sizes of 20–80 participants), with short duration (8–13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. Conclusions Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.

IMPORTANCEBullying is a prevalent and modifiable risk factor for mental health disorders. Although previous studies have supported the effectiveness of anti-bullying programs; their population impact and the association of specific moderators with outcomes are still unclear.OBJECTIVE To assess the effectiveness of school anti-bullying interventions, their population impact, and the association between moderator variables and outcomes.DATA SOURCES A search of Ovid MEDLINE, ERIC, and PsycInfo databases was conducted using 3 sets of search terms to identify randomized clinical trials (RCTs) assessing anti-bullying interventions published from database inception through February 2020. A manual search of reference lists of articles included in previous systematic reviews and meta-analyses was also performed. STUDY SELECTIONThe initial literature search yielded 34 798 studies. Included in the study were articles that (1) assessed bullying at school; (2) assessed the effectiveness of an anti-bullying program; (3) had an RCT design; (4) reported results; and (5) were published in English. Of 16 707 studies identified, 371 met the criteria for review of full-text articles; 77 RCTs were identified that reported data allowing calculation of effect sizes (ESs). Of these, 69 independent trials were included in the final meta-analysis database.DATA EXTRACTION AND SYNTHESIS Random-effects and meta-regression models were used to derive Cohen d values with pooled 95% CIs as estimates of ES and to test associations between moderator variables and ES estimates. Population impact number (PIN), defined as the number of children in the total population for whom 1 event may be prevented by an intervention, was used as an estimate of the population impact of universal interventions targeting all students, regardless of individual risk. MAIN OUTCOMES AND MEASURESThe main outcomes are the effectiveness (measured by ES) and the population impact (measured by the PIN) of anti-bullying interventions on the following 8 variable categories: overall bullying, bullying perpetration, bullying exposure, cyberbullying, attitudes that discourage bullying, attitudes that encourage bullying, mental health problems (eg, anxiety and depression), and school climate as well as the assessment of potential assocations between trial or intervention characteristics and outcomes. RESULTSThis study included 77 samples from 69 RCTs (111 659 participants [56 511 in the intervention group and 55 148 in the control group]). The weighted mean (range) age of participants in the intervention group was 11.1 (4-17) years and 10.8 (4-17) years in the control group. The weighted mean (range) proportion of female participants in the intervention group was 49.9% (0%-100%) and 50.5% (0%-100%) in the control group. Anti-bullying interventions were efficacious in reducing bullying (ES, −0.150; 95% CI, −0.191 to −0.109) and improving mental health problems (ES, −0.205; 95% CI, −0.277 to −0.133) at study end point, with PINs for universal interventions that target the total stud...

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CONTEXT: Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial. OBJECTIVE: To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach.

Background Functional impairment is a defining feature of psychotic disorders. A range of factors has been shown to influence functioning, including negative symptoms, cognitive performance and cognitive reserve (CR). However, it is not clear how these variables may affect functioning in first-episode psychosis (FEP) patients. This 2-year follow-up study aimed to explore the possible mediating effects of CR on the relationship between cognitive performance or specific clinical symptoms and functional outcome. Methods A prospective study of non-affective FEP patients was performed (211 at baseline and 139 at follow-up). CR was entered in a path analysis model as potential mediators between cognitive domains or clinical symptoms and functioning. Results At baseline, the relationship between clinical variables or cognitive performance and functioning was not mediated by CR. At follow-up, the effect of attention (p = 0.003) and negative symptoms (p = 0.012) assessed at baseline on functioning was partially mediated by CR (p = 0.032 and 0.016), whereas the relationship between verbal memory (p = 0.057) and functioning was mediated by CR (p = 0.014). Verbal memory and positive and total subscales of PANSS assessed at follow-up were partially mediated by CR and the effect of working memory on functioning was totally mediated by CR. Conclusions Our results showed the influence of CR in mediating the relationship between cognitive domains or clinical symptoms and functioning in FEP. In particular, CR partially mediated the relationship between some cognitive domains or clinical symptoms and functioning at follow-up. Therefore, CR could improve our understanding of the long-term functioning of patients with a non-affective FEP.