Abstracts

Rationale: TLE with hippocampal sclerosis (TLE-HS) is the most common form of drug-resistant epilepsy in adults. Depression is the most frequent psychiatric disorder (PD) observed in these patients. Basic and clinical studies demonstrate an imbalance of the dopaminergic (DA) system in both conditions. The DA receptors are categorized as two classes nominated as D1-like (DRD1 and DRD5) or D2-like (DRD2, DRD3, and DRD4). The most expressed D2-like receptors in the limbic system are DRD2 and DRD4. Genetic variants which encode proteins related to DA neurotransmission may regulate the levels of DA. The DRD2 rs1800497 polymorphism generates three genotypes CC, TT homozygotes and CT heterozygotes. Relative to the CC homozygotes, T allele carriers show a 30–40% reduction in DRD2 density. The functional DRD4 promoter rs1800955 (−521 T>C) variant was shown to influence DRD4 transcriptional activity. Functional studies on the DRD4 VNTR polymorphism showed that the seven-repeat (long) allele led to a significantly suppressed expression of DRD4 as compared with the two-repeat and four-repeat (short) alleles. In this context, we aimed to: (i) determine the possible association between the DRD2 and DRD4 receptor polymorphisms – DRD2 rs1800497, DRD4 rs1800955 and DRD4 VNTR - and the presence of depression in patients with TLE-HS, and (ii) evaluate the possible association between this variant and susceptibility to develop seizures in TLE-HS. Methods: We assessed 119 patients with 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 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 DRD4 VNTR polymorphism by polynucleotide chain reaction (PCR) amplification of the region of interest followed by capillary electrophoresis system. The DRD2 rs1800497 and DRD4 rs1800955 were genotyped by real-time PCR with TaqMan allele-specific assays. 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: There was no difference between the TLE-HS and control group (p=1.000) and between TLE-HS and MDD without epilepsy group (p=0.740). 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=1.000). In an intragroup comparison, no difference was observed between TLE-HS with MDD and TLE-HS without MDD group (p=0.594). Conclusions: In this series, the polymorphisms related to dopaminergic 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: This work was supported by 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) and CNPq - National Council or Scientific and Technological Development (grant number 308968/2015-8).