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Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine


Gärtner, Matti; Aust, Sabine; Bajbouj, Malek; Fan, Yan; Wingenfeld, Katja; Otte, Christian; Heuser-Collier, Isabella; Böker, Heinz; Hättenschwiler, Josef; Seifritz, Erich; Grimm, Simone; Scheidegger, Milan (2019). Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. European Neuropsychopharmacology, 29(4):501-508.

Abstract

Converging evidence suggests that a single sub-anesthetic dose of ketamine can produce strong and rapid antidepressant effects in patients that do not respond to standard treatment. Despite a considerable amount of research investigating ketamine's mechanisms of action, the exact neuronal targets conveying the antidepressant effects have not been identified yet. Preclinical studies suggest that molecular changes induced by ketamine bring forward large-scale network reconfigurations that might relate to ketamine's antidepressant properties. In this prospective two-site study we measured resting state fMRI in 24 depressed patients prior to, and 24 h after a single sub-anesthetic dose of ketamine. We analyzed functional connectivity (FC) at baseline and after ketamine and focused our analysis on baseline FC and FC changes directly linked to symptom reduction in order to identify neuronal targets that predict individual clinical responses to ketamine. Our results show that FC increases after ketamine between right lateral prefrontal cortex (PFC) and subgenual anterior cingulate cortex (sgACC) are positively linked to treatment response. Furthermore, low baseline FC between these regions predicts treatment outcome. We conclude that PFC-sgACC connectivity may represent a promising biomarker with both predictive and explanatory power.

Abstract

Converging evidence suggests that a single sub-anesthetic dose of ketamine can produce strong and rapid antidepressant effects in patients that do not respond to standard treatment. Despite a considerable amount of research investigating ketamine's mechanisms of action, the exact neuronal targets conveying the antidepressant effects have not been identified yet. Preclinical studies suggest that molecular changes induced by ketamine bring forward large-scale network reconfigurations that might relate to ketamine's antidepressant properties. In this prospective two-site study we measured resting state fMRI in 24 depressed patients prior to, and 24 h after a single sub-anesthetic dose of ketamine. We analyzed functional connectivity (FC) at baseline and after ketamine and focused our analysis on baseline FC and FC changes directly linked to symptom reduction in order to identify neuronal targets that predict individual clinical responses to ketamine. Our results show that FC increases after ketamine between right lateral prefrontal cortex (PFC) and subgenual anterior cingulate cortex (sgACC) are positively linked to treatment response. Furthermore, low baseline FC between these regions predicts treatment outcome. We conclude that PFC-sgACC connectivity may represent a promising biomarker with both predictive and explanatory power.

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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
Uncontrolled Keywords:Pharmacology (medical), Biological Psychiatry, Pharmacology, Neurology, Psychiatry and Mental health, Clinical Neurology
Language:English
Date:1 April 2019
Deposited On:18 Feb 2020 14:46
Last Modified:19 Feb 2020 13:31
Publisher:Elsevier
ISSN:0924-977X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.euroneuro.2019.02.008
PubMed ID:30819549

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