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Título

Genetic Polymorphisms of the Dopamine Receptors Are Not Related With Depression In Temporal Lobe Epilepsy Caused By Hippocampal Sclerosis

Resumo

Purpose: Depression is the most prevalent psychiatric disorder in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). Mechanisms of epilepsy and depression include abnormalities in the dopamine (DA) pathway.

Objective: We aimed to determine the possible association between the most expressed D2-like receptors in the limbic system's polymorphisms and major depressive disorder (MDD) in patients with TLE-HS. Our secondary aim was to evaluate the possible association between these variants and seizure susceptibility in TLE-HS.

Method: We assessed 119 patients with TLE-HS, with and without psychiatric disorders (PD), 146 patients with MDD, and 113 controls. We excluded patients with other epileptic syndromes, dual pathology, or the absence of a structural lesion.
We genotyped the DRD2 rs1800497 and D4 rs1800955 by RT-PCR and D4 VNTR by PCR amplification using the capillary electrophoresis system. Categorical variables were compared between groups by the two-tailed chi-square test and Fisher's exact test, whereas numerical variables were analyzed by the Kruskal-Wallis test. Type I error was set at 5%, and adjustment for multiple testing was carried out by Holm-Bonferroni Sequential Correction.

Results:

rs1800497: There was no difference between the TLE-HS and control (p=1.000); TLE-HS and MDD group (p=0.342); MDD and control (p=1.000) and TLE-HS with MDD and MDD without epilepsy (p=1.000).

rs1800955: There was no difference between the TLE-HS and control (p=1.000); TLE-HS and MDD group (p=0.618); MDD and control (p=0.618) and TLE-HS with MDD and MDD without epilepsy (p=1.000).

D4 VNTR: There was no difference between the TLE-HS and control (p=1.000); TLE-HS and MDD group (p=1.000); MDD and control (p=1.000) and TLE-HS with MDD and MDD without epilepsy (p=1.000).

Conclusion: In this series, the polymorphisms related to DA transmission were not related to the susceptibility to develop TLE-HS or the presence of MDD in patients with TLE-HS. Further studies with larger series are necessary to corroborate these findings.

Funding: FAPESP supported this work — Foundation for the Support of Research in the State of Sao Paulo (grant number: 2013/11361-4) and CAPES — Office for the Advancement of Higher Education (grant number: 1469000). Dr. Valente was also supported by CNPq — National Council or Scientific and Technological Development (grant number: 308968/2015-8).

Keywords: Epilepsy; hippocampal sclerosis; dopamine receptors; genetic polymorphisms; major depressive disorder.