Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression

• Published in: The international journal of neuropsychopharmacology 2021-05, Vol.24 (5), p.383-391
• Main Authors: Rivas-Grajales, Ana Maria, Salas, Ramiro, Robinson, Meghan E, Qi, Karen, Murrough, James W, Mathew, Sanjay J
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Care and treatment; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - physiopathology; Connectome; Depression, Mental; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - physiopathology; Depressive Disorder, Treatment-Resistant - diagnostic imaging; Depressive Disorder, Treatment-Resistant - drug therapy; Depressive Disorder, Treatment-Resistant - physiopathology; Diencephalon; Dosage and administration; Female; Habenula - diagnostic imaging; Habenula - physiopathology; Health aspects; Humans; Ketamine; Ketamine - administration & dosage; Ketamine - pharmacology; Magnetic Resonance Imaging; Male; Middle Aged; Neural circuitry; Outcome Assessment, Health Care; Pharmacology, Experimental; Physiological aspects; Regular s; Testing
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1093/ijnp/pyaa089

Abstract Background Ketamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor–dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states. Methods Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined. Results A reduction in Montgomery–Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P