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Depression and Sleep
Open AccessReview

Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter?

1
Department of Psychiatry and Psychotherapy, Johannes Gutenberg University Medical Center Mainz, Untere Zahlbacher Straße 8, 55131 Mainz, Germany
2
Focus Program Translational Neurosciences, Johannes Gutenberg University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
3
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark
*
Authors to whom correspondence should be addressed.
Shared last authorship.
Int. J. Mol. Sci. 2019, 20(4), 949; https://doi.org/10.3390/ijms20040949
Received: 14 January 2019 / Revised: 15 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
(This article belongs to the Special Issue Molecular Psychiatry)
Gender differences play a pivotal role in the pathophysiology and treatment of major depressive disorder. This is strongly supported by a mean 2:1 female-male ratio of depression consistently observed throughout studies in developed nations. Considering the urgent need to tailor individualized treatment strategies to fight depression more efficiently, a more precise understanding of gender-specific aspects in the pathophysiology and treatment of depressive disorders is fundamental. However, current treatment guidelines almost entirely neglect gender as a potentially relevant factor. Similarly, the vast majority of animal experiments analysing antidepressant treatment in rodent models exclusively uses male animals and does not consider gender-specific effects. Based on the growing interest in innovative and rapid-acting treatment approaches in depression, such as the administration of ketamine, its metabolites or electroconvulsive therapy, this review article summarizes the evidence supporting the importance of gender in modulating response to rapid acting antidepressant treatment. We provide an overview on the current state of knowledge and propose a framework for rodent experiments to ultimately decode gender-dependent differences in molecular and behavioural mechanisms involved in shaping treatment response. View Full-Text
Keywords: gender; sex difference; depression; antidepressant; rapid-acting; antidepressant; Ketamine; endocrinology; (2R,6R)-Hydroxynorketamine; electroconvulsive therapy gender; sex difference; depression; antidepressant; rapid-acting; antidepressant; Ketamine; endocrinology; (2R,6R)-Hydroxynorketamine; electroconvulsive therapy
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Herzog, D.P.; Wegener, G.; Lieb, K.; Müller, M.B.; Treccani, G. Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter? Int. J. Mol. Sci. 2019, 20, 949.

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