Association Between NTRK2 Polymorphisms, Hippocampal Volumes and Treatment Resistance in Major Depressive Disorder

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Nov 25

PMID 38002980

Authors

Marco Paolini

Lidia Fortaner-Uya

Cristina Lorenzi

Sara Spadini

Melania Maccario

Raffaella Zanardi

Cristina Colombo

Sara Poletti

Francesco Benedetti

Affiliations

Soon will be listed here.

Abstract

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 ()-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to and on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology.

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