Whole Blood Transcriptome Analysis in Female Adolescents With Depression Accompanied by Nonsuicidal Self‐Injury and Suicide Attempt

Study Objective Using RNA sequencing (RNA‐seq) on blood samples from depressed female adolescents with nonsuicidal self‐injury (NSSI) or suicide attempt (SA), this study explored links between peripheral blood gene expression and these behaviors. Methods Female adolescents with major depressive disorder (MDD) who were of the same age as the subjects were enrolled in the study and divided into three groups: MDD, NSSI, and NSSI + SA. Whole blood samples were collected for RNA‐seq and bioinformatics analysis. Results Multivariate linear regression analysis revealed that the NADH dehydrogenase iron–sulfur protein 7 ( NDUFS7 ) and C–X–C motif chemokine ligand 10 ( CXCL10 ) were important predictive factors distinguishing the MDD group from the NSSI + SA group. In weighted gene co‐expression network analysis (WGCNA), the blue module showed the greatest significance, with gene expression levels negatively correlated in the MDD group and NSSI group, and strongly positively correlated in the NSSI + SA group, consistent with differences in disease severity between self‐harm and suicide. Conclusion This study revealed the whole‐blood transcriptomic features of female adolescent MDD patients with different behavioral phenotypes. It found that neuroimmune responses, along with core genes NDUFS7 and CXCL10 , are key in the development of NSSI and SA in adolescent females, and could be therapeutic targets. Trial Registration ClinicalTrials.gov identifier: ChiCTR2500107586