TY - JOUR
T1 - Associations of three major physiological stress systems with suicidal ideation and suicide attempts in patients with a depressive and/or anxiety disorder
AU - Wiebenga, Jasper X. M.
AU - Heering, Henriette D.
AU - Eikelenboom, Merijn
AU - van Hemert, Albert M.
AU - van Oppen, Patricia
AU - Penninx, Brenda W. J. H.
N1 - Funding Information: B. Penninx received (non-related) research funding from Boehringer Ingelheim and Jansen Research. The other authors declare that they have no conflict of interest. Funding Information: The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and financial contributions by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Rob Giel Onderzoekscentrum). The authors would like to thank H. de Kluiver (GGZ inGeest Specialized Mental Health Care, Department of Research and Innovation, Amsterdam, The Netherlands) for proofreading the manuscript. Publisher Copyright: © 2022 The Author(s)
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Background: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic–pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. Methods: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). Results: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose–response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. Conclusion: Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality.
AB - Background: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic–pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. Methods: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). Results: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose–response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. Conclusion: Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality.
KW - Anxiety disorder
KW - Autonomic nervous system
KW - Depressive disorder
KW - HPA-axis
KW - Inflammation
KW - Suicide attempt
KW - Suicide ideation
UR - http://www.scopus.com/inward/record.url?scp=85125285709&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbi.2022.02.021
DO - https://doi.org/10.1016/j.bbi.2022.02.021
M3 - Article
C2 - 35202735
SN - 0889-1591
VL - 102
SP - 195
EP - 205
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
ER -