Association of SLC6A4 methylation with long-term outcomes after stroke: focus on the interaction with suicidal ideation

• Published in: Scientific reports Vol. 11; no. 1; pp. 2710 - 10
• Main Authors: Kang, Hee-Ju, Lee, Eun-Hye, Kim, Ju-Wan, Kim, Sung-Wan, Shin, Il-Seon, Kim, Joon-Tae, Park, Man-Seok, Cho, Ki-Hyun, Han, Jung-Soo, Lyoo, In Kyoon, Kim, Jae-Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/53/2422; 692/617/375/1370/534; CpG islands; DNA methylation; Homeostasis; Humanities and Social Sciences; Mental disorders; Methylation; multidisciplinary; Regression analysis; Science; Science (multidisciplinary); Serotonin; Serotonin transporter; Stroke; Suicidal ideation; Suicide; Suicides & suicide attempts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81854-9

Serotonin (5-HT) plays an important role in cerebrovascular homeostasis and psychiatric disorders, including suicidality. Methylation of the serotonin transporter gene ( SLC6A4 ) is associated with 5-HT expression. However, the prognostic roles of SLC6A4 methylation and suicidal ideation (SI) in long-term outcomes of stroke have not been evaluated. We investigated the independent and interactive effects of SLC6A4 methylation and SI immediately after stroke on long-term outcomes. Blood SLC6A4 methylation status and SI based on the suicide item of the Montgomery–Åsberg Depression Rating Scale were assessed in 278 patients at 2 weeks after stroke. After the index stroke, cerebro-cardiovascular events by SLC6A4 methylation status and SI were investigated over an 8–14-year follow-up period and using Cox regression models adjusted for a range of covariates. SLC6A4 hypermethylation and SI within 2 weeks of stroke both predicted worse long-term outcomes, independent of covariates. A significant interaction effect of SI and the methylation status of CpG 4 on long-term stroke outcomes was also identified. The association between SLC6A4 methylation and long-term adverse outcomes may be strengthened in the presence of SI within 2 weeks after stroke. Evaluation of methylation and SI status during the acute phase can be helpful when assessing stroke patients.