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

TY - JOUR

T1 - Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter?

AU - Herzog, David

AU - Wegener, Gregers

AU - Lieb, Klaus

AU - Müller, Marianne

AU - Treccani, Giulia

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - (2r,6r)-hydroxynorketamine

KW - Antidepressant

KW - Depression

KW - Electroconvulsive therapy

KW - Endocrinology

KW - Gender

KW - Ketamine

KW - Rapid-acting

KW - Sex difference

UR - http://www.scopus.com/inward/record.url?scp=85063423622&partnerID=8YFLogxK

U2 - 10.3390/ijms20040949

DO - 10.3390/ijms20040949

M3 - Review

C2 - 30813226

SN - 1661-6596

VL - 20

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

IS - 4

M1 - 949

ER -