Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study

J Clin Psychiatry. 2024 Feb 21;85(1):23m14996. doi: 10.4088/JCP.23m14996.


Objective: Adolescent suicide is a major public health problem, and risk of suicide is higher among those with major depressive disorder (MDD), which may be linked to alterations in mitogen- and stress-activated kinase 1 (MSK1) and to defects in executive function. Here, we aimed to investigate the potential impacts of executive function and MSK1 methylation on suicidal ideation in adolescents with MDD.

Methods: The study enrolled 66 drug-naive adolescents who were experiencing their first episode of MDD from February 2019 until October 2020. After 6 weeks of receiving antidepressant treatment, 65 participants remained in the study. Suicidal ideation and depressive severity were assessed using the Hamilton Depression Rating Scale, while executive function was evaluated using the Cambridge Neuropsychological Test Automated Battery. MSK1 methylation was measured using bisulfite DNA analysis.

Results: Among the 66 adolescents with MDD, 43 (65.15%) reported suicidal ideation, while 23 (34.85%) did not. Individuals with suicidal ideation had worse executive function and higher MSK1 methylation than those without suicidal ideation. The MSK1 methylation percentage may predict suicidal ideation in adolescents with MDD (odds ratio [OR] 1.227, 95% CI [1.031 to 1.461]). Improvement in executive function was significantly associated with reduced suicidal ideation during antidepressant treatment (β = -0.200, 95% CI [-0.877 to -0.085]).

Conclusions: Our results strengthen the evidence for a link among MSK1 methylation, executive function, and suicidal ideation in adolescent MDD.

Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033402.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antidepressive Agents / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / genetics
  • Executive Function*
  • Humans
  • Methylation
  • Prospective Studies
  • Ribosomal Protein S6 Kinases, 90-kDa* / genetics
  • Suicidal Ideation*


  • Antidepressive Agents
  • mitogen and stress-activated protein kinase 1
  • Ribosomal Protein S6 Kinases, 90-kDa

Associated data