Habenular connectivity may predict treatment response in depressed psychiatric inpatients

Abstract

Introduction: The habenula (Hb) is a small midbrain structure that signals negative events and may play a major role in the etiology of psychiatric disorders including depression. The lateral Hb has three major efferent connections: serotonergic raphe nuclei, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area/substantia nigra compacta. We wanted to test whether Hb connectivity may be important to predict treatment outcomes in depression patients.

Methods: We studied whether habenular connectivity at admission into a psychiatric clinic can predict treatment response. We used an inpatient sample (N = 175) to assess habenular connectivity (diffusion tensor imaging and resting state functional connectivity (RSFC) between the Hb and its targets) close to admission. In addition, we obtained the Patient Health Questionnaire-depression module (PHQ-9) close to admission and at discharge. Inpatients in the study entered the clinic with at least moderately severe depression (score 15 and up). Inpatients considered treatment resistant had scores of 9 or more at discharge.

Results: Compared to responders, treatment non-responders had lower fractional anisotropy in the right Hb afferent fibers and lower RSFC between right Hb and median raphe, but higher RSFC between left Hb and locus coeruleus. A logistic regression model was significantly different from chance, and explained 27.7% of the variance in treatment resistance (sensitivity = 75%; specificity = 71.9%).

Discussion: The anatomical and functional connectivity of the Hb may be a predictor of treatment success in psychiatric populations. Limitations include the Hb small size and the limited time (5 min) of resting state data obtained.

Keywords: Habenula; Locus coeruleus; Major depression disorder; Raphe nucleus; Resting state functional connectivity; Treatment outcome prediction.