Immune characterization of suicidal behavior in female adolescents

Background: To address the need to identify potential markers of suicide behavior for adolescents (ages 12-18 years), mass cytometry was used to explore the cellular mechanisms that may underpin immune dysregulation in adolescents with recent suicidal behavior. Methods: Peripheral blood mononuclear cell (PBMC) samples from 10 female adolescents with a recent suicide attempt and 4 healthy female adolescents were used. A panel of 30 antibodies was analyzed using mass cytometry. We used two complementary approaches to 1) identify the cell types that significantly differed between the two groups, and 2) explore differences in the expression profile of markers on the surface of these cells. Mass cytometry data were investigated using (Center for Disease Control, 2021) Opt-SNE for dimension reduced (Curtin and Heron, 2019), FlowSOM for clustering, and (Bridge et al., 2006) EgdeR and SAM for statistical analyses. Results: Opt-SNE (a data driven clustering analysis) identified 15 clusters of distinct cell types. From these 15 clusters, cluster 5 (classical monocytes) had statistically lower abundance in suicidal adolescents as compared to healthy controls, whereas cluster 7 (gamma-delta T cells) had statistically higher abundance in suicidal adolescents compared to healthy control. Furthermore, across the 15 cell types, chemokine receptors, CXCR3 (cluster 5) and CXCR5 (clusters 4, 5, 7, and 9), had an elevated expression profile in those with a recent suicide attempt versus healthy controls. Conclusion: This report demonstrates the utility of high dimensional cell phenotyping in psychiatric disorders and provides preliminary evidence for distinct immune dysfunctions in adolescents with recent suicide attempts as compared to healthy controls.