Habenular connectivity may predict treatment response in depressed psychiatric inpatients

Savannah N. Gosnell, Kaylah N. Curtis, Kenia Velasquez, James Chris Fowler, Alok Madan, Wayne Goodman, Ramiro Salas

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalJournal of Affective Disorders
StatePublished - Jan 1 2019


  • Habenula
  • Locus coeruleus
  • Major depression disorder
  • Raphe nucleus
  • Resting state functional connectivity
  • Treatment outcome prediction

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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