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.
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Acknowledgements
We thank the subjects who participated in this study for their invaluable contribution. This work was supported by the Clinical Neuroscience Division National Center for PTSD, K23 MH-101498, Brain and Behavior Foundation (NARSAD New Investigator Award; CGA), R01 MH07895 (DCS), K23 MH-069656, MO1 RR-00071, R01 MH-081870. The Johnson Family Chair for Research, and by the use of resources and facilities at the Michael E. DeBakey VA Medical Center, Houston, Texas (SJM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.
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Abdallah, C., Jackowski, A., Salas, R. et al. The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder. Neuropsychopharmacol 42, 1739–1746 (2017). https://doi.org/10.1038/npp.2017.49
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DOI: https://doi.org/10.1038/npp.2017.49
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