Sarah A Keaton1, Zachary B Madaj2, Patrick Heilman3, LeAnn Smart4, Jamie Grit5, Robert Gibbons6, Teodor T Postolache7, Kimberly Roaten8, Eric D Achtyes9, Lena Brundin10. 1. Department of Physiology, Michigan State University, East Lansing, MI, USA; Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA. 2. Bioinformatics and Biostatistics Core, Van Andel Research Institute, Grand Rapids, MI, USA. 3. Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA. 4. Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA. 5. Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, USA. 6. Center for Health Statistics, Departments of Medicine and Public Health Sciences, University of Chicago, IL, USA. 7. Department of Psychiatry, University of Maryland-Baltimore School of Medicine, Baltimore, MD, USA; Rocky Mountain Mirecc, Denver, CO, USA. 8. Department of Psychiatry, University of Texas Southwestern, Dallas, TX, USA. 9. Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA; Division of Psychiatry & Behavioral Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, USA. Electronic address: Eric.Achtyes@PineRest.org. 10. Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA. Electronic address: Lena.Brundin@vai.org.
Abstract
BACKGROUND: Suicide risk assessments are often challenging for clinicians, and therefore, biological markers are warranted as guiding tools in these assessments. Suicidal patients display increased cytokine levels in peripheral blood, although the composite inflammatory profile in the subjects is still unknown. It is also not yet established whether certain inflammatory changes are specific to suicidal subjects. To address this, we measured 45 immunobiological factors in peripheral blood and identified the biological profiles associated with cross-diagnostic suicide risk and depression, respectively. METHODS: Sixty-six women with mood and anxiety disorders underwent computerized adaptive testing for mental health, assessing depression and suicide risk. Weighted correlation network analysis was used to uncover system level associations between suicide risk, depression, and the immunobiological factors in plasma. Secondary regression models were used to establish the sensitivity of the results to potential confounders, including age, body mass index (BMI), treatment and symptoms of depression and anxiety. RESULTS: The biological profile of patients assessed to be at increased suicide risk differed from that associated with depression. At the system level, a biological cluster containing increased levels of interleukin-6, lymphocytes, monocytes, white blood cell count and polymorphonuclear leukocyte count significantly impacted suicide risk, with the latter two inferring the strongest influence. The cytokine interleukin-8 was independently and negatively associated with increased suicide risk. The results remained after adjusting for confounders. LIMITATIONS: This study is cross-sectional and not designed to prove causality. DISCUSSION: A unique immunobiological profile was linked to increased suicide risk. The profile was different from that observed in patients with depressive symptoms, and indicates that granulocyte mediated biological mechanisms could be activated in patients at risk for suicide.
BACKGROUND: Suicide risk assessments are often challenging for clinicians, and therefore, biological markers are warranted as guiding tools in these assessments. Suicidal patients display increased cytokine levels in peripheral blood, although the composite inflammatory profile in the subjects is still unknown. It is also not yet established whether certain inflammatory changes are specific to suicidal subjects. To address this, we measured 45 immunobiological factors in peripheral blood and identified the biological profiles associated with cross-diagnostic suicide risk and depression, respectively. METHODS: Sixty-six women with mood and anxiety disorders underwent computerized adaptive testing for mental health, assessing depression and suicide risk. Weighted correlation network analysis was used to uncover system level associations between suicide risk, depression, and the immunobiological factors in plasma. Secondary regression models were used to establish the sensitivity of the results to potential confounders, including age, body mass index (BMI), treatment and symptoms of depression and anxiety. RESULTS: The biological profile of patients assessed to be at increased suicide risk differed from that associated with depression. At the system level, a biological cluster containing increased levels of interleukin-6, lymphocytes, monocytes, white blood cell count and polymorphonuclear leukocyte count significantly impacted suicide risk, with the latter two inferring the strongest influence. The cytokine interleukin-8 was independently and negatively associated with increased suicide risk. The results remained after adjusting for confounders. LIMITATIONS: This study is cross-sectional and not designed to prove causality. DISCUSSION: A unique immunobiological profile was linked to increased suicide risk. The profile was different from that observed in patients with depressive symptoms, and indicates that granulocyte mediated biological mechanisms could be activated in patients at risk for suicide.
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