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

Abstract

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.

Fig. 1

Daily fluctuations in (A) salivary cortisol and (B) salivary α-amylase. Error bars represent standard errors of the mean.

Fig. 2

Variations in (A) salivary cortisol and (B) salivary α-amylase in response to the Trier Social Stress Test. Error bars represent standard errors of the mean.

Fig. 3

Effect of Trier Social Stress Test on the Delis–Kaplan Executive Function System (A) Word–Colour Inhibition Test inhibition–switching condition errors and (B) Trail Making Test switching condition errors. Scores represent scaled scores (higher scores represent fewer errors).