TY - JOUR
T1 - Immune characterization of suicidal behavior in female adolescents
AU - Chin Fatt, Cherise R.
AU - Farrar, J. David
AU - Jha, Manish K.
AU - Minhajuddin, Abu
AU - Mayes, Taryn
AU - Foster, Jane A.
AU - Trivedi, Madhukar H.
N1 - Funding Information:
These studies were funded in part by the Elizabeth Jordan Harris Foundation , the W.W. Caruth Jr. Foundation , and the Hersh Foundation . The content is solely the responsibility of the authors and does not necessarily represent the official views of the various funding organizations. We thank the participants, families, staff, and colleagues who made this project possible, and Kathryn Forbes for administrative support.
Funding Information:
Dr. Trivedi has served as a consultant or advisor for Alkermes Inc., Alto Neuroscience Inc, Axsome Therapeutics, Boegringer Ingelheim, GH Research, GreenLight VitalSign6 Inc, Heading Health, inc., Janssen Pharmaceutical, Legion Health, Merck Sharp & Dohme Corp., Mind Medicine Inc., Navitor, Neurocrine Biosciences Inc., Noema Pharma AG, Orexo US Inc., Otsuka Canada Pharmaceutical Inc, Otsuka Pharmaceutical Development & Commercialization, Inc. (MDD Section Advisor), SAGE Therapeutics, Signant Health, and Takeda Pharmaceuticals Inc. He receives editorial compensation from Oxford University Press. Dr. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. Dr. Foster has served on the Scientific Advisory Board for MRM Health NL and has received consulting/speaker fees from Klaire Labs, Takeda Canada and Rothman, Benson, Hedges Inc. Dr. Chin Fatt, Dr. Farrar, Dr. Minhajuddin, and Mrs. Mayes have no conflicts of interest to report.
Funding Information:
These studies were funded in part by the Elizabeth Jordan Harris Foundation, the W.W. Caruth Jr. Foundation, and the Hersh Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the various funding organizations. We thank the participants, families, staff, and colleagues who made this project possible, and Kathryn Forbes for administrative support.
Publisher Copyright:
© 2022
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbih.2022.100499
DO - 10.1016/j.bbih.2022.100499
M3 - Article
C2 - 36120101
AN - SCOPUS:85138789720
SN - 2666-3546
VL - 25
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100499
ER -