Decreased Hippocampal Serotonin 5HT Expression in Mesial Temporal Lobe of Epilepsy Patients

Introduction: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is a surgically remediable epilepsy with a relatively high prevalence and psychiatric comorbidities. Depressive disorders may occur in up to 25% of MTLE-HS patients suggesting a common molecular mechanism underlying both conditions.

Objective: To compare the gene expression comprising serotonin 5HT and 5HT, noradrenaline (NA) ADRA1A, and ADRA2A receptors in the hippocampus of MTLE-HS patients with and without major depression.

Methods: A cross-sectional study allocated 31 patients in three groups: MTLE-HS without psychiatric diagnosis (MTLE-HS group), MTLE-HS with major depression (MTLE-HS-D group) and a control group consisting of healthy volunteers without any neurological or psychiatric disorders. Demographic and clinical characteristics were compared among groups. Gene expression of receptors were analyzed using general linear mixed models (GLMM), with an unstructured matrix, normal link.

Results: The three groups showed a similar distribution regarding age, gender (p > 0.16), history of initial precipitating injury, family history of epilepsy, monthly frequency of seizures, side of hippocampal sclerosis, interictal spike distribution and anti-seizure medications did not differ between MTLE-HS and MTLE-HS-D groups (p > 0.05). We observed a greater expression of the 5HT1A receptor in the control group when compared to the MTLE-HS (P = .004) and MTLE-HS-D (P = .007). Nevertheless, we did not observe any difference when MTLE-HS and MTLE-HS-D groups were compared to the controls for the ADRA1A (P = .931; P = .931), ADRA2A (P = .120; P = .121) and 5HT2A (P = .638; P = .318, respectively) gene expression.

Conclusion: Mesial temporal lobe epilepsy related to hippocampal sclerosis and MTLE-HS-D patients showed a lowered expression of the 5HT1A receptors when compared with the controls adjusted for age and schooling. Data suggest that temporal lobe epilepsy plasticity may affect serotonin receptors, which may lead to more frequent cases of major depression in this population. More studies comprising wider samples are necessary to confirm these results; they also should investigate serotonin reuptake drugs as an adjuvant therapeutic option for MTLE-HS disorder.