title: The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder.
abstract: Animal models of depression repeatedly showed stress-induced nucleus accumbens (NAc) hypertrophy. Recently, ketamine was found to normalize this stress-induced NAc structural growth. Here, we investigated NAc structural abnormalities in major depressive disorder (MDD) in two cohorts. Cohort A included a cross-sectional sample of 34 MDD and 26 healthy control (HC) subjects, with high-resolution magnetic resonance imaging (MRI) to estimate NAc volumes. Proton MR spectroscopy (1H MRS) was used to divide MDD subjects into two subgroups: glutamate-based depression (GBD) and non-GBD. A separate longitudinal sample (cohort B) included 16 MDD patients who underwent MRI at baseline then 24 h following intravenous infusion of ketamine (0.5 mg/kg). In cohort A, we found larger left NAc volume in MDD compared to controls (Cohen's d=1.05), but no significant enlargement in the right NAc (d=0.44). Follow-up analyses revealed significant subgrouping effects on the left (d⩾1.48) and right NAc (d⩾0.95) with larger bilateral NAc in non-GBD compared to GBD and HC. NAc volumes were not different between GBD and HC. In cohort B, ketamine treatment reduced left NAc, but increased left hippocampal, volumes in patients achieving remission. The cross-sectional data provided the first evidence of enlarged NAc in patients with MDD. These NAc abnormalities were limited to patients with non-GBD. The pilot longitudinal data revealed a pattern of normalization of left NAc and hippocampal volumes particularly in patients who achieved remission following ketamine treatment, an intriguing preliminary finding that awaits replication.
authors.affiliation: Clinical Neuroscience Division, National Center for PTSD, VA CT Healthcare System, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Chadi G
authors.identifier: http://orcid.org/0000-0001-5783-6181
authors.initials: CG
authors.lastname: Abdallah
authors.affiliation: LiNC, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Andrea
authors.identifier: http://orcid.org/0000-0001-8842-5406
authors.initials: A
authors.lastname: Jackowski
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.|Research Care Line, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Salas
authors.affiliation: Clinical Neuroscience Division, National Center for PTSD, VA CT Healthcare System, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Gupta
authors.affiliation: LiNC, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.|Center of Mathematics, Computation and Cognition. Universidade Federal do ABC, Santo Andre, Brazil.
authors.forename: João R
authors.initials: JR
authors.lastname: Sato
authors.affiliation: Departments of Radiology, Psychiatry and Biophysics, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Coplan
authors.affiliation: Departments of Radiology, Psychiatry and Biophysics, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.|Mental Health Care Line, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D018698:Glutamic Acid; D007649:Ketamine