Abstracts

Rationale: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most prevalent psychiatric disorder observed in these patients. Pathophysiological mechanisms of epilepsy and psychiatric disorders include abnormalities in the serotonin (5-HT) pathway. Genetic variants which encode proteins related to serotonergic neurotransmission may regulate the levels of 5-HT. Two polymorphisms in serotonin transporter gene (5-HTT), a 44 bp insertion/deletion in the 5´regulatory region (5-HTT-LPR) and a VNTR polymorphism in the second intron (5-HTT-VNTR) modulate transcription. The primary goal of this study was to determine the possible association between 5-HTT polymorphisms and the presence of mood disorders in patients with TLE-HS. Our secondary aim was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. Methods: We assessed 119 patients with unequivocal TLE-HS, with and without psychiatric disorders, 146 patients diagnosed with major depressive disorder (MDD) without epilepsy and psychotic features, and  113 healthy volunteers from the general population with no personal or family history of epilepsy or PD. We assessed individuals by a clinical interview held by SCID-I/P. We excluded patients with other epileptic syndromes, dual pathology or absence of a structural lesion. We evaluated epilepsy-related factors such as the age of onset, seizure types and frequency status epilepticus, febrile seizures and other personal antecedents of note; drug-resistant epilepsy and; side of the lesion. Individuals were genotyped for the 5HTT-LPR and 5HTT-VNTR polymorphisms by PCR amplification of the region of interest using the capillary electrophoresis system (Fragment Analyzer^TM). Categorical variables were compared between groups by the 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: 5-HTT-LPR: There was no difference between the TLE-HS and control group (p=0.626) and between TLE-HS and MDD without epilepsy group (p=1.000). There was also no difference between MDD without epilepsy and control group (p=0.728) and TLE-HS with MDD and MDD without epilepsy group (p=1.000). In an intragroup comparison, no difference was observed between TLE-HS with MDD and TLE-HS without MDD group (p=1.000). 5-HTT-VNTR: There was no difference between the TLE-HS and control group (p=0.790) and between TLE-HS and MDD without epilepsy group (p=1.000). There was also no difference between MDD without epilepsy and control group (p=1.000) and TLE-HS with MDD and MDD without epilepsy group (p=0.974). In an intragroup comparison, no difference was observed between TLE-HS with MDD and TLE-HS without MDD group (p=1.000). Conclusions: In this series, the polymorphisms related to serotonergic transmission are not related to the susceptibility to develop TLE-HS or the presence of mood disorders in patients with TLE-HS. Further studies with larger series are necessary to corroborate these findings.  Funding: FAPESP — Foundation for the Support of Research in the State of Sao Paulo (grant number: 2013/11361-4)CAPES — Office for the Advancement of Higher Education (grant number: 1469000)CNPq — National Council or Scientific and Technological Development (grant number: 308968/2015-8)