The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder
This open-label cohort study (n=76) examined the effects of ketamine (35mg/70kg) on gray matter enlargement in relation to glutamate-based and non-glutamate-based abnormalities in patients with depression. They found that patients with non-glutamate-based depression exhibited an enlarged Nucleus Accumbens and that ketamine treatment leads to the rapid reduction in Nucleus Accumbens and an enlargement of the hippocampus only within patients who achieve remission of their depressive symptoms.
Authors
- Sanjay Mathew
- Chadi Abdallah
Published
Abstract
Introduction
Animal models of depression repeatedly showed stress-induced nucleus accumbens (NAc) hypertrophy. Recently, ketamine was found to normalize this stress-induced NAc structural growth.
Methods
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).
Results
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.
Discussion
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.
Research Summary of 'The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder'
Introduction
Major depressive disorder (MDD) is prevalent, often chronic, and frequently resistant to standard antidepressants. Preclinical work has repeatedly shown that chronic stress produces contrasting patterns of structural plasticity across brain regions: hippocampal atrophy on the one hand and hypertrophy of the nucleus accumbens (NAc) on the other. Ketamine, a rapid-acting antidepressant, has been shown in animal models to reverse stress-induced NAc hypertrophy. Translating these findings to humans has been limited by a paucity of in vivo data on NAc volumes in MDD. Abdallah and colleagues set out to test two linked hypotheses. First, they asked whether people with MDD have larger NAc volumes than healthy controls. Second, in a separate sample, they examined whether a single intravenous ketamine infusion (0.5 mg/kg) would alter NAc volume 24 hours after treatment, and whether such changes related to clinical remission. A further aim was to explore whether an MDD subgrouping based on medial prefrontal cortical (mPFC) GABA/Glx measures—defined as glutamate-based depression (GBD) versus non-GBD—would differentially show NAc abnormalities, consistent with a proposed dichotomy of amino acid– versus monoamine-based structural pathology.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Abdallah, C. G., Jackowski, A., Salas, R., Gupta, S., Sato, J. R., Mao, X., Coplan, J. D., Shungu, D. C., & Mathew, S. J. (2017). The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder. Neuropsychopharmacology, 42(8), 1739-1746. https://doi.org/10.1038/npp.2017.49
References (2)
Papers cited by this study that are also in Blossom
Abdallah, C. G., Averill, L. A., Collins, K. A. et al. · Neuropsychopharmacology (2016)
Ari, A., Abdallah, C. G., Sanacora, G. et al. · Annual Review of Medicine (2014)
Cited By (10)
Papers in Blossom that reference this study
Calder, A. E., Hase, A., Hasler, G. · Molecular Psychiatry (2024)
Agnorelli, C., Spriggs, M. J., Godfrey, K. et al. · Preprints (2024)
Zhou, Y-L., Wang, C., Lan, X-F. et al. · Frontiers in Psychiatry (2022)
Keeler, J. L., Treasure, J., Juruena, M. F. et al. · Nutrients (2021)
Siegel, J. S., Palanca, B. J. A., Ances, B. M. et al. · Psychopharmacology (2021)
Abdallah, C. G., Averill, L. A., Gueorguieva, R. et al. · Neuropsychopharmacology (2020)
Hashimoto, K. · Psychiatry and Clinical Neurosciences (2019)
Abdallah, C. G., Sanacora, G., Duman, R. S. et al. · Chronic Stress (2018)
Liu, W., Wang, C., Zhan, Y. et al. · Journal of Psychopharmacology (2018)
Abdallah, C. G., Averill, C. L., Salas, R. et al. · Biological Psychiatry (2017)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.