Serotonin gene polymorphisms and psychiatry comorbidities in temporal lobe epilepsy

Abstract

INTRODUCTION: Among epileptic patients, those with temporal lobe epilepsy (TLE) are at risk to develop psychiatric disorders. Evidence suggests that the association of psychiatric disorders with epilepsy might be related to common biological substrates. Studies support that serotonin (5-HT) may also contribute to a predisposition to epilepsy. The 5-HTTLPR and 5-HTTVNTR polymorphisms in the 5-HTT gene and the C-1019G polymorphism in the 5-HT1A gene have been studied in psychiatric diseases. As far as we know, this is the first study evaluating a possible genetic involvement in the development of psychiatric comorbidities in epilepsy. OBJECTIVE: It is biologically plausible that alterations in serotonin-related genes may be involved in higher susceptibility to psychiatric disease in the individuals with TLE. Here we report results of an association study of serotonin gene polymorphisms and psychiatry comorbidities in TLE. METHODS: Case-control study of 155 patients with temporal lobe epilepsy. We evaluate the influence of 5-HTTLPR and 5-HTTVNTR polymorphisms in the 5-HTT gene and the C-1019G polymorphism in the 5-HT1A gene in psychiatric comorbidities of TLE. RESULTS: After logistic regression, female sex (O.R.=2.38; 95%CI 1.08 to 5.28; p=0.03) and the presence of C allele of 5-HT1A C-1019G polymorphism (O.R.=2.82; 95% CI 1.02 to 7.81; p=0.04) remained independent risk factors for anxiety disorders in temporal lobe epilepsy (O.R.=2.82; 95% CI 1.02 to 7.81; p=0.04). CONCLUSION: C allele of 5-HT1A C-1019G polymorphism is independent risk factor for anxiety disorders in temporal lobe epilepsy. Other studies will shade some light on molecular mechanisms involved in psychiatric comorbidities in epilepsy. Financiamento: CNPQ e FIPE-HCPA

The impact of cue learning, trait anxiety and genetic variation in the serotonin 1A receptor on contextual fear

“…In the present study C-carriers display the largest context-FPS and the largest cue-FP-VAS. This may appear contradictory, but C-carriers demonstrated higher amygdala reactivity in an imaging study (Fakra et al, 2009) and increased risk for anxiety disorders in patients with temporal lobe epilepsy was found in C-carriers (Schenkel et al, 2012). As has been argued for other polymorphisms, speaking of an allele that confers just 'risk' may not accurately describe the different effects the 5-HTR 1A polymorphism under study (Beste et al, 2011).…”

“…Also, G-carriers of this polymorphism were shown to have higher neuroticism and related personality traits (Strobel et al, 2003). In contrast, increased amygdala activity (Fakra et al, 2009) and risk for anxiety disorders in patients with temporal lobe epilepsy (Schenkel et al, 2012) were reported in C-carriers of this 5-HTR 1A polymorphism. Based on all these findings, variability in the regulation of contextual anxiety through different functionality of the serotonin 1 A receptor may contribute to individual differences in contextual responding, as discussed above.…”

Association study of functional polymorphisms of dopaminergic pathway in epilepsy‐related factors of temporal lobe epilepsy in Brazilian population

“…However, surprisingly, a study found a more homogeneous ancestry throughout Brazil than previously estimated, with 60-78% being of European background [26]. In addition, the south and southeast regions of Brazil present a higher percentage of European ancestry, as already discussed previously [27].…”

Hippocampal serotonin depletion is related to the presence of generalized tonic–clonic seizures, but not to psychiatric disorders in patients with temporal lobe epilepsy

“…The heterogeneity of the group in terms of the type of PD might have interfered with our results. However, it is also possible that other mechanisms that are related to 5-HT are correlated with the presence of PD, such as altered serotonin receptor or transporter functions (Drevets et al, 1999;Hasler et al, 2007;Hung et al, 2011;Sargent et al, 2000;Schenkel et al, 2011). Nonetheless, other mechanisms (Gattaz et al, 2011;Kandratavicius et al, 2013b) are also probably related to these findings.…”