The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. Imaging data was collected from 10 centers worldwide, including 474 subjects with 22q11DS (age=18.2±8.6; 46.9% female) and 315 typically-developing, matched controls (age=18.0±9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen’s d=0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d=−1.01/−1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

BackgroundSynchronous written conversations (or “chats”) are becoming increasingly popular as Web-based mental health interventions. Therefore, it is of utmost importance to evaluate and summarize the quality of these interventions.ObjectiveThe aim of this study was to review the current evidence for the feasibility and effectiveness of online one-on-one mental health interventions that use text-based synchronous chat.MethodsA systematic search was conducted of the databases relevant to this area of research (Medical Literature Analysis and Retrieval System Online [MEDLINE], PsycINFO, Central, Scopus, EMBASE, Web of Science, IEEE, and ACM). There were no specific selection criteria relating to the participant group. Studies were included if they reported interventions with individual text-based synchronous conversations (ie, chat or text messaging) and a psychological outcome measure.ResultsA total of 24 articles were included in this review. Interventions included a wide range of mental health targets (eg, anxiety, distress, depression, eating disorders, and addiction) and intervention design. Overall, compared with the waitlist (WL) condition, studies showed significant and sustained improvements in mental health outcomes following synchronous text-based intervention, and post treatment improvement equivalent but not superior to treatment as usual (TAU) (eg, face-to-face and telephone counseling).ConclusionsFeasibility studies indicate substantial innovation in this area of mental health intervention with studies utilizing trained volunteers and chatbot technologies to deliver interventions. While studies of efficacy show positive post-intervention gains, further research is needed to determine whether time requirements for this mode of intervention are feasible in clinical practice.

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.

Objective 22q11.2 deletion syndrome (22q11.2DS) is associated with a >20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., “second hits”) that may contribute to schizophrenia expression. Methods Through an international consortium we obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), we compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: with and, at age ≥25 years, without a psychotic disorder. We assessed whether genes overlapped by rare CNVs were over-represented in functional pathways relevant to schizophrenia. Results Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene-sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a step-wise logistic regression model (p=0.00062) and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had on average more genes overlapped (p=0.0058). The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. Conclusions The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness, and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.