Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium.

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs.
Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients.
Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31).
Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.
Competing Interests: Conflict of Interest Dr. Arnold reported holding the Alberta Innovates Translational Health Chair in Child and Youth Mental Health outside the submitted work. Prof. Mataix-Cols receives royalties for contributing articles to UpToDate, Wolters Kluwer Health and fees from Elsevier for editorial tasks (all unrelated to the submitted work). Dr. Narayanaswamy reported Government of India grants DST INSPIRE faculty grant IFA12-LSBM-26 and BT/06/IYBA/2012 outside the submitted work. Dr. Reddy reported Government of India grants SR/S0/HS/0016/2011 and BT/PR13334/Med/30/259/2009 outside the submitted work. Dr. Venkatasubramanian reported Wellcome-DBT India Alliance grant 500236/Z/11/Z outside the submitted work. Dr. Simpson reported Biohaven Research support for a clinical trial and royalties from UpToDate, Inc. and Cambridge University Press outside the submitted work. Dr. Soreni reported support from Lundbeck-IIT outside the submitted work. Dr. Walitza has received in the last 3 years royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz; Her work was supported in the last 3 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds (all unrelated to the submitted work). Dr. Thompson has received a research grant from Biogen, Inc., unrelated to the topic of this paper.
(Copyright © 2022. Published by Elsevier B.V.)