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Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine


Herrera-Melendez, Ana; Stippl, Anna; Aust, Sabine; Scheidegger, Milan; Seifritz, Erich; Heuser-Collier, Isabella; Otte, Christian; Bajbouj, Malek; Grimm, Simone; Gärtner, Matti (2021). Gray matter volume of rostral anterior cingulate cortex predicts rapid antidepressant response to ketamine. European Neuropsychopharmacology, 43:63-70.

Abstract

Ketamine was recently approved for treatment resistant depression. However, despite its therapeutic potential, about 50% of patients do not show improvement under this therapy. In this prospective two-site study, we investigated baseline brain structural predictors for rapid symptom improvement after a single subanesthetic ketamine infusion. Furthermore, given the preclinical evidence and findings from a pilot study in a clinical population that ketamine induces rapid neuroplasticity, we performed an exploratory investigation of macroscopic changes 24 h post-treatment. T1-weighted MRI brain images from 33 depressed patients were acquired before and 24 h after a single ketamine infusion and analyzed using voxel-based morphometry (VBM). Additionally, we performed a region of interest (ROI)-based analysis of structures that have previously been shown to play a role in the antidepressant effects of ketamine: bilateral hippocampus, nucleus accumbens, anterior cingulate cortex, and thalamus. A whole-brain regression analysis showed that greater baseline volume of the bilateral rostral anterior cingulate cortex (rACC) significantly predicts rapid symptom reduction. The right ACC showed the same association in the ROI analysis, while the other regions yielded no significant results. Exploratory follow-up analyses revealed no volumetric changes 24 h after treatment. This is the first study reporting an association between pretreatment gray matter volume of the bilateral rACC and the rapid antidepressant effects of ketamine. Results are in line with previous investigations, which highlighted the potential of the rACC as a biomarker for response prediction to different antidepressant treatments. Ketamine-induced volumetric changes may be seen at later time points.

Abstract

Ketamine was recently approved for treatment resistant depression. However, despite its therapeutic potential, about 50% of patients do not show improvement under this therapy. In this prospective two-site study, we investigated baseline brain structural predictors for rapid symptom improvement after a single subanesthetic ketamine infusion. Furthermore, given the preclinical evidence and findings from a pilot study in a clinical population that ketamine induces rapid neuroplasticity, we performed an exploratory investigation of macroscopic changes 24 h post-treatment. T1-weighted MRI brain images from 33 depressed patients were acquired before and 24 h after a single ketamine infusion and analyzed using voxel-based morphometry (VBM). Additionally, we performed a region of interest (ROI)-based analysis of structures that have previously been shown to play a role in the antidepressant effects of ketamine: bilateral hippocampus, nucleus accumbens, anterior cingulate cortex, and thalamus. A whole-brain regression analysis showed that greater baseline volume of the bilateral rostral anterior cingulate cortex (rACC) significantly predicts rapid symptom reduction. The right ACC showed the same association in the ROI analysis, while the other regions yielded no significant results. Exploratory follow-up analyses revealed no volumetric changes 24 h after treatment. This is the first study reporting an association between pretreatment gray matter volume of the bilateral rACC and the rapid antidepressant effects of ketamine. Results are in line with previous investigations, which highlighted the potential of the rACC as a biomarker for response prediction to different antidepressant treatments. Ketamine-induced volumetric changes may be seen at later time points.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Pharmacology
Life Sciences > Neurology
Health Sciences > Neurology (clinical)
Health Sciences > Psychiatry and Mental Health
Life Sciences > Biological Psychiatry
Health Sciences > Pharmacology (medical)
Uncontrolled Keywords:Pharmacology (medical), Biological Psychiatry, Pharmacology, Neurology, Psychiatry and Mental health, Clinical Neurology
Language:English
Date:1 February 2021
Deposited On:01 Feb 2021 06:32
Last Modified:02 Feb 2021 21:00
Publisher:Elsevier
ISSN:0924-977X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.euroneuro.2020.11.017
PubMed ID:33309459

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