Medial prefrontal-thalamic white matter microstructure is associated with harm avoidance in OCD: a discovery and transdiagnostic replication study

Abstract Identifying neural mechanisms underlying harm avoidance and incompleteness in OCD and other psychiatric disorders is critical for improving diagnostic precision and developing targeted treatments. However, little is known about the neural pathways underlying these symptom dimensions across clinical populations. The goal of this study was to use diffusion MRI to replicate and extend prior findings in OCD to a transdiagnostic sample of healthy controls (HC) and individuals with Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), and non-OCD disorders (e.g., anxiety, post-traumatic stress disorder). Connections between prefrontal (dorsomedial, dorsolateral, ventromedial, and ventrolateral) and subcortical regions (thalamus and striatum) were reconstructed using whole brain tractography in 38 HC (mean age SD = 30.97 10.62), 47 OCD (mean age [SD = 32.34 12.23), 21 OCPD (mean age SD = 35.67 14.65), and 20 Non-OCD (mean age SD = 35.90 14.26) participants. Fractional anisotropy (FA) was derived for each connection. Harm avoidance and incompleteness symptom dimensions were assessed using the Obsessive-Compulsive Trait Core Dimensions Questionnaire. In a first replication model, including individuals with OCD and HC, higher left ( β = 0.29, P = 0.009, Q = 0.048) and right ( β = 0.30, P = 0.005, Q = 0.0048) dorsomedial PFC-thalamus FA was associated with higher harm avoidance, with the left connection also associated with higher incompleteness ( β = 0.29, P = 0.009, Q = 0.048). In additional models adding in OCPD and non-OCD participants, only associations among left ( β = 0.20, P = 0.027, Q = 0.040) and right ( β = 0.18, P = 0.035, Q = 0.045) dorsomedial PFC-thalamus FA and harm avoidance remained significant. There were no associations involving PFC-striatum connections. Dorsomedial PFC-thalamus FA was associated with harm avoidance, but less so with incompleteness. Our findings suggest that higher dorsomedial PFC-thalamic FA is associated with higher harm avoidance across diagnostic groups, providing transdiagnostic neural targets for future treatment developments.