Subcortical brain volume, regional cortical thickness and cortical surface area across attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD)

Abstract

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

“…Our work will clarify whether OCD subjects across the globe show altered structure and function within frontal-striatal, frontal-limbic, and frontal-parietal circuits, as we hypothesize. If we see the structural abnormalities found in several meta-and mega-analyses [34,35,140,141], including that of ENIGMA-OCD [36,37], it will provide strong evidence for the link between these structural abnormalities and OCD psychopathology. Moreover, we will test how multimodal imaging measures are linked to discrete domains of neurocognitive or clinical profiles, enabling us to make new discoveries about the association between abnormalities in structural and functional connectivity and cognitive and clinical dimensions of OCD.…”

“…First, many have been single-site studies in small and historically Western, educated, industrialized, rich, and democratic (WEIRD) samples [27], and reproducibility of findings across sites has been variable. Meta-and mega-analyses (like those done by the OCD Brain Imaging Consortium (OBIC) and the initiative for Enhancing Neuroimaging and Genetics through Meta-analyses (ENIGMA) [34][35][36][37]) have been conducted, resulting in very large samples. These analyses pool existing data from multiple sites that use different inclusion criteria, clinical measures, and imaging methods.…”

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

“…ENIGMA's meta-analyses estimated the size and precision of the effects after pooling evidence from multiple cohorts, and they also ranked the neuroimaging effect sizes of findings emerging from case-control comparisons, thereby setting the stage for deeper, secondary analyses aiming to explore potential moderators of psychiatric and neurological disease. More recently, many ENIGMA groups have moved beyond cohort level meta-analyses to pooled, or 'mega'-analyses (Using brain volumetric data from ENIGMA's OCD, ADHD, and ASD working groups, Boedhoe et al 12 compared meta-analysis to mega-analyses that model site or cohort effects as random effects, showing broad agreement. Mega-analyses allow more sophisticated statistical adjustments as they pool more information across cohorts; meta-analyses tend to be more efficient when ethical, legal or logistic constraints govern or restrict individual-level data transfer (e.g., genome-wide genetic data).…”

“…Building on this work, the focus of the ENIGMA disorder-specific WGs now goes beyond traditional diagnostic boundaries. As these first large-scale studies are being completed, ENIGMA is beginning to identify shared and distinct neuroimaging patterns in brain disorders with known genetic or clinical overlap 11,12 , and to delineate the role of transdiagnostic risk factors (e.g., childhood trauma) and clinical phenomena (e.g., suicidal thoughts and behaviors). In addition, ENIGMA's genetic studies are now analyzing imaging and genetics data from more than 50,000 people to uncover genetic markers that most robustly associated with brain structure and function, or imaging derived neurobiological traits related to various disease conditions [13][14][15][16] .…”

ENIGMA MDD: Seven Years of Global Neuroimaging Studies of Major Depression through Worldwide Data Sharing

“…preprocessing pipelines and analysis protocols, ENIGMA is uniquely positioned to perform cross-disorder comparison studies, and several initiatives are ongoing. These include projects comparing brain morphology in SCZ, BD, and MDD as well as in neurodevelopmental disorders (autism spectrum disorder, attention deficit hyperactivity disorder, OCD, and Tourette's syndrome)167 . These studies are being performed using a mega-analytic rather than a metaanalytic framework, to better account for various covariates and possible confounds across groups and study sites.…”