Immunological correlates of suicidality among adolescents with internalizing symptoms

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Suicide is a leading cause of death in adolescents and young adults globally. Well-established risk factors for suicide are depression and past suicide attempts. People experiencing suicidality may represent a distinct neurobiological group of people with depression. Because converging evidence has implicated inflammation in depression, 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. Adolescents underwent semi-structured interviews and completed self-reported measures to assess psychopathology, including suicidality (suicidal ideation, plans, or attempts). 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. Among 126 participants, 29 were healthy controls and 97 participants had internalizing symptoms; within the clinical group, 57 experienced suicidality. Three immune analytes differed between healthy controls, suicidal, and non-suicidal adolescents with internalizing symptoms in the LPS condition: Flt-3L ( p FDR = 0.0246), GM-CSF ( p FDR = 0.0246), and IFN-γ ( p FDR = 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 reduced 41 analytes to several common immune factors across experimental conditions, with Flt-3L, GM-CSF, and IFN-γ all loading heavily onto immune factors that were hypoactive in suicidality. Through this data-driven approach, we detected further associations between suicidality and immune factors across all conditions. Peripheral immune function may be distinctly altered in adolescent suicidality. Future work should examine immune-suicidality relationships longitudinally. • Peripheral immune function may be distinctly altered in adolescent suicidality. • Suppressed cytokines (incl. Flt-3L, GM-CSF, and IFN-γ) after an inflammatory stressor may reflect a pro-suicidal immune state. • Factor analysis showed Flt-3L, GM-CSF, and IFN-γ loading heavily onto immune factors that were hypoactive in suicidality. • Data-driven approach with factor analysis revealed subtle associations between suicidality and immune dysfunction.

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