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 (PD) observed in these patients. Pathophysiological mechanisms of epilepsy and PD include abnormalities in the serotonin (5HT) pathway. Genetic variants which encode proteins related to serotonergic neurotransmission may regulate the levels of 5HT. An upstream variable number of tandem repeats polymorphism in monoamine oxidase A (MAOA) gene (MAOA-uVNTR) affect the transcriptional efficiency of the MAOA promoter and MAOA enzyme activity. The primary goal of this study was to determine the possible association between MAOA-uVNTR polymorphism and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. Methods: We assessed 119 patientswith unequivocal TLE-HS, with and without PD; 146 patients diagnosed with major depressive disorder (MDD) without epilepsy and psychotic features, and  113 healthy volunteers from 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 structural lesion. We evaluated epilepsy-related factors such as 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 MAOA-uVNTR polymorphism by PCR amplification of the region of interest using the capillary electrophoresis system (Fragment AnalyzerTM).Categorical variables were compared between groups by the Fisher’s exact test, whereas numerical variables were compared by the Kruskal-Wallis test. Since the MAOA gene is located on the X chromosome, we used the classification of Sabol et al. (1998) and Caspi et al.(2002) to designate alleles as either low or high activity. We grouped apart female who were heterozygous. Type I error was set at 5%, and adjustment for multiple testing was carried out by Holm-Bonferroni Sequential Correction. Results: No difference was observed between the TLE-HS and control group (p=0.681) and between TLE-HS and MDD without epilepsy group (p=0.799). No difference was noted between MDD without epilepsy and control group (p=1.000) and TLE-HS with MDD and MDD without epilepsy group (p=1.000). In a intragroup comparison, no difference was observed between TLE-HS with MDD and TLE-HS without MDD group (p=0.168). Conclusions: Our work suggests that MAOA uVNTR polymorphism is 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: This work was supported by FAPESP - 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. Dr. Valente is also supported by CNPq - National Council for Scientific and Technological Development (grant number 308968/2015-8).