Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy

- TrkB is encoded by NTRK2 gene and binds to BDNF.
- BDNF-TrkB signaling pathway is involved in mood disorders.
- We test if NTRK2 variants were associated with mood in epilepsy.
- We found that NTRK2 variant was associated with depressive disorders in epilepsy.
- NTRK2 variants might be used as biomarker for depressive disorders in epilepsy.

RationalePsychiatric comorbidities are highly prevalent in epilepsy, adding an important burden to the disease and profoundly affecting the quality of life of these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and several lines of evidence suggest that the association of depression with epilepsy might be related to common biological substrates. In this study, we test whether NTRK2 allele variants are associated with mood disorders or depressive disorders in patients with TLE.MethodsAn association study of 163 patients with TLE. The NTRK2 variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and epilepsy patients with mood disorders or depressive disorders were compared to epilepsy patients without mood disorders or depressive disorders.ResultsIn our TLE cohort, 76 patients (46.6%) showed mood disorders. After logistic regression, independent risk factors for mood disorders in TLE were female sex, presence of concomitant anxiety disorders, and genetic variations in rs1867283 and rs10868235 NTRK2 variants. Depressive disorders accounted for this results and independent variables associated with depressive disorders in TLE were female sex (OR = 2.59; 95%CI = 1.15-5.82; p = 0.021), presence of concomitant anxiety disorders (OR = 3.72; 95%CI = 1.71-8.06; p = 0.001) or psychotic disorders (OR = 3.86; 95%CI = 1.12-13.25; p = 0.032), A/A genotype in the rs1867283 NTRK2 gene (OR = 3.06; 95%CI = 1.25-7.50; p = 0.015) and C/C genotype in the rs10868235 NTRK2 gene (OR = 3.54; 1.55-8.08; p = 0.003). Similarly, these genotypes also remained independently and significantly associated with depressive disorders when patients with depressive disorders were compared to TLE patients without any psychiatric comorbidity.ConclusionIn the present study, female sex, presence of concomitant anxiety or psychotic disorders, and specific allelic variations in the NTRK2 gene were independently associated with mood disorders or depressive disorders in TLE. If our results were confirmed, variants in the NTRK2 gene could be considered as risk factors or biomarkers for depressive disorders in patients with TLE.