CHOROID PLEXUS VOLUME AS A BIOMARKER OF KETAMINE-RELATED IMPROVEMENT IN IRRITABILITY IN ADULTS WITH MAJOR DEPRESSIVE DISORDER

Major depressive disorder (MDD) may be associated with abnormalities in choroid plexus volume. A recent report found association of larger choroid plexus volume with greater improvement with oral antidepressants in individuals with MDD. However, association of choroid plexus volume with changes in rapid-acting antidepressants like ketamine remains poorly understood. This exploratory analyses utilized data from individuals with MDD (n=61) and healthy controls (n=40) from a study (NCT05046184) evaluating neurocircuit mechanisms of irritability where individuals with MDD were randomized to four infusions of ketamine versus midazolam over a two-week period. Freesurfer version 7.1.1 was used to segment choroid plexus (CP) and adjusted for estimated total intracranial volume (eTIV). Association of CP (right and left separately) volume with baseline clinical features and with differential changes in irritability with ketamine versus midazolam based on CР volume were assessed. Mean (SD) of eTIVnormalized right and left CP volumes were 3.1 (1.27) and 3.4 (1.16), respectively. CP volume was not associated with diagnostic status (MDD versus HC), systemic inflammation (creactive protein), and irritability at baseline (all p > 0.20). There was a significant CP-volume-by treatment-by-time interaction for left (F=2.33; dF=5, 242; p=0.0433) and right (F=2.33; dF=5, 242; p=0.0433) where reductions in irritability with ketamine versus midazolam were greater in those with larger CP volumes as compared to those with smaller CP volumes. We found preliminary evidence for differential improvement in irritability with ketamine versus midazolam based on volume of choroid plexus. Replication and mechanistic studies elucidating the link between CP volume and treatment-related change in irritability are needed.