Immunological correlates of suicidality among adolescents with internalizing symptoms

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Background: Suicide is the second leading cause of death in adolescents and young adults in the United States. Well-established risk factors for suicide are depression and past suicide attempts. People experiencing suicidality may represent a distinct neurobiological subgroup. Converging evidence has implicated inflammation in depression. Here we sought to investigate relationships between suicidality and immune markers in youth experiencing diverse mood and anxiety symptoms. We hypothesized that adolescents with suicidality would exhibit a unique immune signature. Methods: Adolescents underwent semi-structured interviews and completed self-reported measures to assess psychopathology, including suicidality. Fasting blood samples were collected, cultured with and without lipopolysaccharide (LPS) to stimulate an inflammatory response, and analyzed for 41 immune analytes. To assess how immune function related to suicidality categorically and dimensionally, we conducted group comparisons and correlations while controlling for multiple comparisons using false discovery rate (FDR). To further uncover subtle immune-suicidality relationships, we employed a data-driven approach using factor analysis to extract major immune factors, each of which was subsequently correlated with suicidality measures.Results: Among 126 participants, 29 were healthy controls and 97 participants had psychopathology; within the clinical group, 57 experienced suicidality. Three immune analytes differed between suicidal and non-suicidal adolescents in the LPS condition: Flt-3L (pFDR = 0.0246), GM-CSF (pFDR = 0.0246), and IFN-γ (pFDR = 0.0246). These analytes were negatively correlated with the Beck Scale for Suicide Ideation (BSSI): Flt-3L (ρ = −0.19, p = 0.04); GM-CSF (ρ = −0.26, p = 0.004); IFN-γ (ρ =−0.33, p = 0.0003). GM-CSF also negatively correlated with number of suicide attempts (ρ = −0.39, p = 0.003). Factor analysis revealed further associations between immune factors, derived from full 41-analyte panels, and suicidality across all sample culture conditions. Conclusions: Peripheral immune function may be distinctly altered in adolescent suicidality. Future work should examine immune-suicidality relationships longitudinally.

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