In the second additional approach, we studied age‐by‐medication interactions in 2,176 OCD patients (1,040 medicated/1,136 unmedicated) and 2,003 healthy controls, using a general linear model (Ivanov et al., 2019). Medicated OCD patients, unmedicated OCD patients, and healthy controls all showed decreasing brain‐wide cortical thickness, surface area, and subcortical volume with increasing age (p < .0005) in most regions. Effects of medication (p < .001–.0005) and age‐by‐medication interactions (p < .05–.0005) were detected in 46 cortical and 7 subcortical brain regions. Accordingly, in certain regions (e.g., supramarginal gyrus, lateral occipital cortex), child and/or adolescent medicated OCD patients had thicker cortex than unmedicated patients. Adult medicated OCD patients, however, had thinner cortex than unmedicated OCD patients. Effects on cortical thickness were strongest for tricyclic antidepressants, but were also present for serotonin reuptake inhibitors (SRIs) and benzodiazepines. One (speculative) explanation of the differential effects of medication on cortical thickness in pediatric versus adult patients with OCD is the combination of treatment‐associated slowing of the neuronal regressive changes (synapse loss and neurite pruning) and slowing (in children) and acceleration (in adults) of the progressive white‐matter myelination of normal aging.
