OPEN Foundation

J. Sato

The Nucleus Accumbens and Ketamine Treatment in Major Depressive Disorder

March 8, 2017 / Depression, Ketamine, Neuroscience, Papers, Psychopharmacology / By / , , , , , ,

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.
Abdallah, C. G., Jackowski, A., Salas, R., Gupta, S., Sato, J. R., Mao, X., … & Mathew, S. J. (2017). The nucleus accumbens and ketamine treatment in major depressive disorder. Neuropsychopharmacology, 1, 8. 10.1038/npp.2017.49
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Acute Biphasic Effects of Ayahuasca

September 30, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Psychopharmacology, Publications / By / , , , , ,

Abstract

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca’s compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it’s potential therapeutic effects is offered.

Schenberg E.E., Alexandre J.F.M., Filev R., Cravo A.M., Sato J.R., Muthukumaraswamy S.D., et al. (2015) Acute Biphasic Effects of Ayahuasca. PLoS ONE 10(9): e0137202. http://dx.doi.org/10.1371/journal.pone.0137202
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30 April - Q&A with Rick Strassman

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