title: Hippocampal volume and the rapid antidepressant effect of ketamine.
abstract: Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Åsberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus (r = 0.66; p = 0.01), but not the right hippocampus (r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high (r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom (df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants.
authors.affiliation: Clinical Neuroscience Division, National Center for Post-traumatic Stress Disorder (PTSD), West Haven, CT, USA Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA chadi.abdallah@yale.edu.
authors.forename: Chadi G
authors.initials: CG
authors.lastname: Abdallah
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Salas
authors.affiliation: Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jackowski
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Baldwin
authors.affiliation: Department of Psychiatry, 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: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA Mental Health Care Line, Michael E Debakey Veterans' Administration (VA) Medical Center, Houston, TX, USA.
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015415:Biomarkers; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000473:pathology; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D007649:Ketamine
keywords: Antidepressant; depression; hippocampus; ketamine; magnetic resonance imaging; major depressive disorder; refractory patients