Torres Carolina Machado, Siebert Marina, Bock Hugo, Mota Suelen Mandelli, Castan Juliana Unis, Scornavacca Francisco, de Castro Luiza Amaral, Saraiva-Pereira Maria Luiza, Bianchin Marino Muxfeldt
Medical Sciences, Universidade Federal do Rio Grande do Sul, Brazil; Basic Research and Advanced Investigations in Neurology (BRAIN), Experimental Research Centre, Centro de Tratamento de Epilepsia Refratária (CETER), Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
Laboratory of Genetic Identification, Experimental Research Centre, Hospital de Clinicas de Porto Alegre, Brazil.
Epilepsy Behav. 2017 Jun;71(Pt A):65-72. doi: 10.1016/j.yebeh.2017.03.030. Epub 2017 May 24.
Psychiatric 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.
An 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.
In 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.
In 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.
精神疾病共病在癫痫中极为普遍，给该疾病增添了重要负担，并深刻影响这些患者的生活质量。颞叶癫痫（TLE）患者尤其容易患上抑郁症，多条证据表明抑郁症与癫痫之间的关联可能与共同的生物学基础有关。在本研究中，我们测试NTRK2等位基因变异是否与TLE患者的情绪障碍或抑郁障碍相关。
对163例TLE患者进行关联研究。所研究的NTRK2变异包括rs1867283、rs10868235、rs1147198、rs11140800、rs1187286、rs2289656、rs1624327、rs1443445、rs3780645和rs2378672。所有患者均接受《精神疾病诊断与统计手册》第四版（DSM-IV）的结构化临床访谈，并将患有情绪障碍或抑郁障碍的癫痫患者与未患情绪障碍或抑郁障碍的癫痫患者进行比较。
在我们的TLE队列中，76例患者（46.6%）出现情绪障碍。经过逻辑回归分析，TLE患者情绪障碍的独立危险因素为女性、伴有焦虑症以及NTRK2基因rs1867283和rs10868235变异。抑郁障碍导致了这一结果，TLE患者抑郁障碍的独立相关变量为女性（比值比[OR]=2.59；95%置信区间[CI]=1.15 - 5.82；p=0.021）、伴有焦虑症（OR=3.72；95%CI=1.71 - 8.06；p=0.001）或精神病性障碍（OR=3.86；95%CI=1.12 - 13.25；p=0.032）、NTRK2基因rs1867283的A/A基因型（OR=3.06；95%CI=1.25 - 7.50；p=0.015）以及NTRK2基因rs10868235的C/C基因型（OR=3.54；1.55 - 8.08；p=0.003）。同样，当将患有抑郁障碍的患者与无任何精神疾病共病的TLE患者进行比较时，这些基因型也仍然独立且显著地与抑郁障碍相关。
在本研究中，女性、伴有焦虑或精神病性障碍以及NTRK2基因的特定等位基因变异与TLE患者的情绪障碍或抑郁障碍独立相关。如果我们的结果得到证实，NTRK2基因变异可被视为TLE患者抑郁障碍的危险因素或生物标志物。
