Dataset Information

Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder.

ABSTRACT: Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target-the KCNQ-type potassium channel-for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabine (also known as retigabine) on reward circuitry and clinical symptoms in patients with MDD. Eighteen medication-free individuals with MDD currently in a major depressive episode were enrolled in an open-label study and received ezogabine up to 900?mg/day orally over the course of 10 weeks. Resting-state functional magnetic resonance imaging data were collected at baseline and posttreatment to examine brain reward circuitry. Reward learning was measured using a computerized probabilistic reward task. After treatment with ezogabine, subjects exhibited a significant reduction of depressive symptoms (Montgomery-Asberg Depression Rating Scale score change: -13.7?±?9.7, p?

SUBMITTER: Tan A

PROVIDER: S-EPMC6494706 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder.

Tan Aaron A Costi Sara S Morris Laurel S LS Van Dam Nicholas T NT Kautz Marin M Whitton Alexis E AE Friedman Allyson K AK Collins Katherine A KA Ahle Gabriella G Chadha Nisha N Do Brian B Pizzagalli Diego A DA Iosifescu Dan V DV Nestler Eric J EJ Han Ming-Hu MH Murrough James W JW

Molecular psychiatry 20181101 6

Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target-the KCNQ-type potassium channel-for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabi ...[more]

PMID: 30385872

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Project description:Neurodevelopmental explanations for adolescent substance use have focused on heightened sensitivity of mesolimbic circuitry, centered on the ventral striatum (VS). Recent evidence suggests that, relative to adults, adolescents show a stronger link between reinforcement learning and episodic memory for rewarding outcomes and greater functional connectivity between the VS and hippocampus, which may reflect a heightened reward modulation of memory. However, a link between VS-hippocampal circuitry and adolescent substance use has yet to be established. Two separate studies were conducted to evaluate whether variation in VS-hippocampal resting-state functional connectivity (rs-FC) predicts subsequent adolescent substance use exposure. A pilot study (Study 1) was conducted in 19 youth recruited from a high sociodemographic risk population (N = 19; mean age = 13.3 SD = 1.4; 14 females; 47% Black Non-Hispanic, 32% White Non-Hispanic). To replicate results of Study 1, Study 2 utilized data from the National Consortium on Adolescent Neurodevelopment and Alcohol (N = 644; mean age = 16.3 SD = 2.5; 339 females; 11% Black Non-Hispanic, 11% Hispanic/Latino, 66% White Non-Hispanic). Resting-state fMRI data were collected at a baseline time point and lifetime and past year self-reported substance use was collected at a follow up visit. Regression models tested whether baseline VS-hippocampal rs-FC predicted substance use exposure at follow up, as measured by an index score reflecting the number of substance classes (e.g., alcohol, marijuana) tried and overall frequency of use. Across both studies, higher VS-hippocampal rs-FC at baseline predicted greater substance use exposure at follow up (pFWE < 0.05). These data provide the first evidence linking increased VS-hippocampal connectivity with greater adolescent substance use exposure. Results fit with the emerging idea that variation in adolescent substance use may relate to not only individual differences in mesolimbic sensitivity to reward, but also to an individuals' memory sensitivity to reward as measured by connectivity between canonical memory and reward regions.

Dataset Information

Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder.

Publications

Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder.

Similar Datasets

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