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Original Investigation | Meta-analysis

Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder A Comparative Meta-analysis

Luke J. Norman, MSc1; Christina Carlisi, BA1; Steve Lukito, MSc1; Heledd Hart, PhD1; David Mataix-Cols, PhD2; Joaquim Radua, MD, PhD2,3,4; Katya Rubia, PhD1
[+] Author Affiliations
1Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England
2Department of Clinical Neuroscience, Karolinska Institut, Stockholm, Sweden
3FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain
4Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England
JAMA Psychiatry. 2016;73(8):815-825. doi:10.1001/jamapsychiatry.2016.0700.
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Importance  Patients with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) share impaired inhibitory control. However, it is unknown whether impairments are mediated by shared or disorder-specific neurostructural and neurofunctional abnormalities.

Objective  To establish shared and disorder-specific structural, functional, and overlapping multimodal abnormalities in these 2 disorders through a voxel-based meta-analytic comparison of whole-brain gray matter volume (GMV) and functional magnetic resonance imaging (fMRI) studies of inhibition in patients with ADHD and OCD.

Data Sources  Literature search using PubMed, ScienceDirect, Web of Knowledge, and Scopus up to September 30, 2015.

Study Selection  Whole-brain voxel-based morphometry (VBM) or fMRI studies during inhibitory control comparing children and adults with ADHD or OCD with controls.

Data Extraction and Synthesis  Voxel-wise meta-analyses of GMV or fMRI differences were performed using Seed-based d-Mapping. Regional structure and function abnormalities were assessed within each patient group and then a quantitative comparison was performed of abnormalities (relative to controls) between ADHD and OCD.

Main Outcomes and Measures  Meta-analytic disorder-specific and shared abnormalities in GMV, in inhibitory fMRI, and in multimodal functional and structural measures.

Results  The search revealed 27 ADHD VBM data sets (including 931 patients with ADHD and 822 controls), 30 OCD VBM data sets (928 patients with OCD and 942 controls), 33 ADHD fMRI data sets (489 patients with ADHD and 591 controls), and 18 OCD fMRI data sets (287 patients with OCD and 284 controls). Patients with ADHD showed disorder-contrasting multimodal structural (left z = 1.904, P < .001; right z = 1.738, P < .001) and functional (left z = 1.447, P < .001; right z = 1.229, P < .001) abnormalities in bilateral basal ganglia/insula, which were decreased in GMV and function in patients with ADHD relative to those with OCD (and controls). In OCD patients, they were enhanced relative to controls. Patients with OCD showed disorder-specific reduced function and structure in rostral and dorsal anterior cingulate/medial prefrontal cortex (fMRI z = 2.113, P < .001; VBM z = 1.622, P < .001), whereas patients with ADHD showed disorder-specific underactivation predominantly in the right ventrolateral prefrontal cortex (z = 1.229, P < .001). Ventromedial prefrontal GMV reduction was shared in both disorders relative to controls.

Conclusions and Relevance  Shared impairments in inhibitory control, rather than representing a transdiagnostic endophenotype in ADHD and OCD, were associated with disorder-differential functional and structural abnormalities. Patients with ADHD showed smaller and underfunctioning ventrolateral prefrontal/insular-striatal regions whereas patients with OCD showed larger and hyperfunctioning insular-striatal regions that may be poorly controlled by smaller and underfunctioning rostro/dorsal medial prefrontal regions.

Figures in this Article


Place holder to copy figure label and caption
Results of Voxel-Based Morphometry (VBM) and Functional Magnetic Resonance Imaging (fMRI) Meta-analyses for Each Disorder and the Comparison Between Disorders

A, Results of VBM meta-analysis for, from top to bottom, patients with attention-deficit/hyperactivity disorder (ADHD) relative to controls, patients with obsessive-compulsive disorder (OCD) relative to controls, the comparison between ADHD (vs controls) and OCD (vs controls), and conjunction/disjunction analysis of ADHD and OCD abnormalities (vs controls). The vmOFC GMV deficit is shared between disorders, while the insula/putamen GMV deficit is dissociated between disorders, that is, larger in OCD and smaller in ADHD. B, Results of fMRI meta-analysis for, from top to bottom, patients with ADHD relative to controls, patients with OCD relative to controls, and the comparison between OCD (vs controls) and ADHD (vs controls). C, Multimodal fMRI-VBM conjunction/disjunction analysis for, from top to bottom, overlapping deficits in patients with ADHD relative to controls, overlapping deficits in patients with OCD relative to controls, and the comparison between patients with OCD (vs controls) and patients with ADHD (vs controls). Green indicates increased in patients with OCD vs controls. Warm colors (yellow in ADHD, red in OCD) indicate decreased in patients vs controls. Orange indicates shared decreases in patients relative to controls. Purple indicates regions that were disjunctive across modalities (ie, increased in one but decreased in the other) in ADHD compared with OCD (vs controls).

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