Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

OBJECTIVE: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children's Health, Russia.

BACKGROUND: The aim of this study was to investigate the efficacy of etanercept treatment and to identify predictors of response to therapy within 12 months in patients with juvenile idiopathic arthritis (JIA) without systemic manifestations. METHODS: A total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories. RESULTS: One year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset. CONCLUSION: Almost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.