Dysregulation of the sympathetic nervous system, hypothalamic–pituitary–adrenal axis and executive function in individuals at risk for suicide

Dysregulation of the sympathetic nervous system, hypothalamic–pituitary–adrenal axis and executive function in individuals at risk for suicide


J Psychiatry Neurosci 2012;35(6):399-408

Alexander McGirr, MSc; Gabriel Diaconu, MD; Marcelo T. Berlim, MD, MSc; Jens C. Pruessner, PhD; Rebecca Sablé, MA; Sophie Cabot, BA; Gustavo Turecki, MD, PhD

McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que.


Background: Suicidal behaviour aggregates in families, and the hypothalamic–pituitary–adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function.

Methods: In this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST.

Results: Despite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of inhibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independent of major depression.

Limitations: The sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide.

Conclusions: Blunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.

Submitted Sept. 17, 2009; Revised Jan. 31, 2010; Accepted Mar. 30, 2010.

Acknowledgments: This study was supported in part by the Canadian Institute of Health Research (MOP 57924). Dr. Turecki is a Fonds de la recherché en santé chercheur boursier.

Competing interests: None declared for Mr. McGirr and Ms. Cabot and Drs. Diaconu, Pruessner, Sablé and Turecki. Dr. Berlim has received a grant from the National Alliance for Research on Schizophrenia and Depression.

Contributors: Drs. Turecki and Sablé and Mr. McGirr were involved in the conception and design of the study. Mr. McGirr, Ms. Cabot, and Dr. Diaconu acquired the data, which was analyzed by Drs. Diaconu, Pruessner and Berlim. Drs. Diaconu and Pruessner and Mr. McGirr wrote the manuscript, which was revised by Drs. Sablé, Turecki and Berlim and Ms. Cabot. All authors approved the final version submitted for publication.

DOI: 10.1503/jpn.090121

Correspondence to: Dr. G. Turecki, McGill Group for Suicide Studies, Douglas Hospital Research Centre, McGill University, 6875 LaSalle Blvd., Montréal QC H4H 1R3; gustavo.turecki@mcgill.ca