Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders:a randomized clinical trial

Background: Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations. Virtual reality-based CBT (VR-CBT) could improve therapy efficacy as exposure and behavioral experiments in VR can be optimized, individualized, and carried out in a safe environment. Few VR-CBT studies exist for paranoid ideations and there is a need for large-scale, methodologically rigorous trials. Methods: This study is a randomized, assessor-blinded parallel-groups multi-center superiority clinical trial, fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients diagnosed with schizophrenia spectrum disorder, including schizotypal disorder (ICD-10 F20-29), will be allocated to either 10 sessions of symptom-specific CBT-VR plus treatment as usual-versus 10 sessions of standard symptom-specific CBT for paranoid ideations (CBT) plus treatment as usual. All participants will be assessed at baseline, treatment end (3 months post baseline), and then 9 months post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. Independent assessors blinded to the treatment will evaluate the outcome. Analysis of outcome will be carried out with the intention to treat principles. The primary outcome is ideas of social reference measured with Green Paranoid Thought Scale Part A (GPTS-A) at the cessation of treatment at 3 months post baseline. Secondary outcomes are ideas of persecution (GPTS-B), Social Interaction Anxiety Scale (SIAS), Personal and Social Performance scale (PSP), Safety Behavior Questionnaire (SBQ), and CANTAB Emotion Recognition Task. Discussion: The trial will elucidate whether VR-CBT can enhance therapy efficacy for paranoid ideations. Additionally, Trial findings will provide evidence on the effectiveness and cost-effectiveness of VR-CBT for paranoid ideations that can guide the possible dissemination and implementation into clinical practice

Copy number deletion burden is associated with cognitive, structural, and resting-state network differences in patients with schizophrenia

Total burden of copy number deletions has been implicated in schizophrenia risk and has been associated with reduced cognitive functioning. The current study aims to replicate the cognitive findings and investigate regional grey and white matter volumes. Moreover, it will explore resting-state networks for correlations between functional connectivity and total deletion burden. All imaging differences will be investigated for correlations with cognitive differences. Seventy-eight patients with chronic schizophrenia, who formed a subset of a large genome-wide association study (GWAS), were assessed for intelligence, 34 had structural magnetic resonance imaging, 33 had resting-state functional magnetic resonance imaging, and 32 had diffusion tensor imaging (DTI). Total deletion burden was negatively associated with IQ performance and positively associated with regional volumes in the striatum bilaterally and in the right superior temporal gyrus and white-matter in the corpus callosum. Correlations were identified between deletion burden and both hyper and hypoconnectivity within the default-mode network and hypoconnectivity within the cognitive control network. The functional connectivity correlations with deletion burden were also correlated with the IQ differences identified. Total deletion burden affects regional volumes and resting-state functional connectivity in key brain networks in patients with schizophrenia. Moreover, effects of deletions on cognitive functioning in may be due to inefficiency of key brain networks as identified by dysconnectivity in resting-state networks

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders