Cross-species quantification of the effect of ketamine on gray matter microstructure in obsessive-compulsive disorder

Motivation: Obsessive-compulsive disorder (OCD) is a chronic illness which may involve aberrant gray matter morphology. Ketamine, a rapid-acting antidepressant which induces structural neuroplasticity, decreases OCD symptoms. Therefore, gray matter microstructure could give insights and biomarkers for OCD symptom reduction. Goal(s): To characterize microstructure in OCD and how ketamine modulates it. Approach: Diffusion tensor and neurite orientation density and dispersion imaging were assessed in human OCD patients and OCD model mice before and after ketamine. Results: OCD patients and model mice show altered microstructure within cortico-striato-thalamo-cortical circuitry, primarily concentrated in subcortex for mice and cortex for humans. Ketamine-treated OCD model mice show increased neurite density. Impact: Gold standard approaches for preclinically quantifying drug-induced structural neuroplasticity involve histology and therefore cannot be applied for clinical purposes. We investigated across species whether gray matter microstructure quantification could bridge this gap in the context of ketamine's rapid anti-obsessional effects.