Hippocampal and amygdala subfield volumes in obsessive-compulsive disorder differ according to medication status

Intro Although it has been suggested that the hippocampus and amygdala (HA) are involved in the neurobiology of obsessive-compulsive disorder (OCD), volumetric findings have been inconsistent. Furthermore, the HA consist of heterogenous anatomic units with specific functions and cytoarchitecture, and little work has been undertaken on the volumetry of these subfields in OCD. Methods T1-weighted images from 381 patients with OCD and 338 healthy controls (HCs) from the OCD Brain Imaging Consortium were segmented to produce twelve hippocampal subfields and nine amygdala subfields using FreeSurfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age, quadratic effects of age, sex, site, and whole HA volume. Given evidence of confounding effects of clinical characteristics on brain volumes in OCD, we also performed subgroup analyses to examine subfield volume in relation to comorbid anxiety and depression, medication status, and symptom severity. Results Patients with OCD and HCs did not significantly differ in HA subfield volume. However, medicated patients with OCD had significantly smaller hippocampal dentate gyrus ( p FDR =0.042, d =-0.26) and molecular layer ( p FDR =0.042, d=-0.29) and larger lateral ( p FDR =0.049, d =0.23) and basal ( p FDR =0.049, d =0.25) amygdala subfields than HCs. Unmedicated patients had significantly smaller hippocampal CA1 (pFDR=0.016, d=-0.28) than HCs. No association was detected between any subfield volume and OCD severity. Conclusion Differences in HA subfields between OCD and HCs are dependent on medication status, in line with previous work on other brain volumetric alterations in OCD. This emphasizes the importance of considering psychotropic medication in neuroimaging studies of OCD. ### Competing Interest Statement Prof Mataix-Cols receives royalties from UpToDate, Inc, outside the submitted work.