Background: 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, and little work has been undertaken on the volumetry of the

heterogeneous

anatomic units of HA, with their specific functions and cytoarchitecture, in OCD. We sought to explore potential sources

of heterogeneity in brain volumes by performing a separate analysis for people with and without psychotropic medication use, as well as

the association of subfield volumes with OCD symptom severity. Methods: We segmented T1-weighted images from people with OCD

and healthy controls in the OCD Brain Imaging Consortium to produce 12 hippocampal subfields and 9 amygdala subfields using Free-

Surfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age and quadratic effects

of age, sex, site, and whole HA volume. We also performed subgroup analyses to examine subfield volume in relation to comorbid

anxiety and depression, medication status, and symptom severity. We corrected all analyses for multiple comparisons using the false

discovery rate (FDR). Results: We included images from 381 people with OCD and 338 healthy controls. These groups did not significantly

differ in HA subfield volumes. However, medicated people with OCD had significantly smaller volumes in the hippocampal dentate

gyrus (pFDR = 0.04, d = –0.26) and molecular layer (pFDR = 0.04, d = –0.29), and larger volumes in the lateral (pFDR = 0.049, d = 0.23) and

basal (pFDR = 0.049, d = 0.25) amygdala subfields, than healthy controls. Unmedicated people with OCD had significantly smaller volumes

in the hippocampal cornu ammonis sector 1 (pFDR = 0.02, d = –0.28) than controls. We did not detect associations between any

subfield volume and OCD severity. Limitations: We used cross-sectional data, which limits the interpretation of our analysis.

Conclusion:

Differences in HA subfields between people with OCD and healthy controls 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.