The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Abstract

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = −0.15 to −0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

“…The influence of medication on FC resembles previous work from ENIGMA-OCD on brain structure, where thinner cortices (in adults) and smaller surface areas (in children) were restricted to medicated patients (3,18). Similarly, smaller thalamic volume in adults (49) and microstructural alterations in white matter in OCD were mainly driven by medicated patients Previous ENIGMA-OCD classification analyses based on structural MRI pointed in the same direction, with low overall classification performance between all patients versus controls (AUC=0.57-0.62) and higher classification performance for medicated patients than for unmedicated patients versus controls (AUC=0.69 and 0.60, respectively) (19). But while classification between medicated and unmedicated patients based on structural MRI reached over 0.80 AUC (19), the same classification in this study was 0.56-0.64 AUC.…”

“…This could suggest that thalamic hyperconnectivity with sensorimotor cortical areas may disrupt higher-order corticocortical connectivity within sensorimotor (sub)networks. Interestingly, a recent ENIGMA-OCD study also demonstrated thalamic aberrations, with unmedicated pediatric patients showing larger volumes and adults showing smaller volumes compared to controls (49). These findings provide further support that the thalamus is a crucial hub in the CSTC circuits and plays a vital role in the pathophysiology underlying OCD.…”

Obsessive-compulsive symptoms and resting-state functional characteristics in pre-adolescent children from the general population

“…This could reflect a difference in OCS severity. Morphological thalamus differences have primarily been reported in clinical OCD studies (Weeland Kasprzak, et al, 2022), while population-based studies found that OCS-related functional differences are not associated with thalamus morphology (Alexander-Bloch et al, 2021;Pagliaccio et al, 2021;Suñol et al, 2021). The structure-function relationship in the brain is complex and remains heavily debated (Suárez et al, 2020).…”

“…Also, insight into the underlying neurocircuitry of OCD may lead towards more precise treatment strategies targeting specific circuits. Megaanalyses on morphometry have shown that OCD patients exhibit robust age-dependent subcortical differences, with larger thalamus volume observed in pediatric patients and smaller volume in adults patients (Weeland Kasprzak, et al, 2022). We recently showed that children from a community-based sample with clinical-level OCS (i.e.…”

Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration

“…In addition, both similarities and differences have been noted with the spectrum of childhood onset disorders that often occur comorbid with TS. For example, higher thalamic volume was also noted in the pediatric OCD ( 36 , 59 – 62 ), whereas lower thalamic volume has been reported in ADHD ( 63 – 65 ). Lower gray or white matter volumes in the orbito-frontal cortex was seen in TS ( 9 , 31 , 58 , 66 – 69 ) and also in the ADHD and OCD ( 18 ).…”