Resilience and vulnerability factors influence the cortisol awakening response in individuals vulnerable to suicide

Highlights

• Lower levels of trait resilience were associated with significantly lower total cortisol awakening responses over 7 days.

• Higher levels of socially prescribed perfectionism, trait worry and impulsivity were associated with significantly lower total cortisol awakening responses over 7 days.

• Suicide group membership has an indirect effect on total CAR via trait worry

Abstract

Suicide is a global health issue. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, has been identified as one potential risk factor. Evidence is emerging to suggest that different psychological factors may be associated with increased resilience and vulnerability in this context. The current study investigated whether trait resilience, social support, socially prescribed perfectionism, trait worry and trait impulsivity influenced the cortisol awakening response (CAR) over a 7-day study in individuals vulnerable to suicide. 142 participants with a history of suicidal attempt or ideation (suicide vulnerability group; n = 95) and with no suicide risk history (control group; n = 47) were recruited. Participants completed baseline questionnaires before commencing a 7-day study where they provided cortisol samples immediately upon waking, at 15 min, 30 min and 45 min on 7 consecutive days. Higher worry, socially prescribed perfectionism and impulsivity, lower resilience and social support were found in the suicide vulnerability group compared to the control group. Lower levels of resilience, higher levels of socially prescribed perfectionism, worry and impulsivity were associated with significantly lower total CAR. Suicide group membership was also found to have an indirect effect on total CAR via trait worry. The current findings show for the first time, that these well-known psychological risk factors for suicide are associated with smaller total cortisol awakening responses. Researchers ought to elucidate the precise causal mechanisms linking these traits, CAR and suicide risk in order to develop interventions to help build resilience in vulnerable populations.

Introduction

Suicide is a major global health issue (WHO, 2019). Close to 800,000 people die by suicide each year worldwide and there are 25 million nonfatal suicide attempts annually (Centers for Disease Control and Prevention, 2016; WHO, 2019). As a consequence, understanding, predicting and preventing suicide has been the focus of enormous scientific effort (O'Connor and Nock, 2014; van Heeringen and Mann, 2014). A myriad of psychological, social, psychiatric and neurobiological factors have been found to be associated with suicide risk and vulnerability (O’Connor and Kirtley, 2018; O'Connor and Nock, 2014; van Heeringen and Mann, 2014; van Orden et al., 2010). One avenue of recent investigation has focussed attention on the role of the hypothalamic-pituitary-adrenal (HPA) axis and the stress response system (Giletta et al., 2015, Melhem et al., 2016; McGirr et al., 2010; O’Connor et al., 2016, 2017, O'Connor et al., 2020a, O'Connor et al., 2020b). Specifically, researchers have begun to explore HPA axis functioning following acute laboratory stressors in vulnerable and non-vulnerable groups, as well as recently the relationships between naturally fluctuating cortisol levels and suicide behavior (e.g., Giletta et al., 2015, Melhem et al., 2016, O'Connor et al., 2017; O'Connor et al., 2020a).

The key aim of the laboratory-based stress studies has been to examine whether cortisol reactivity to stress can differentiate individuals who have a history of suicide attempt or ideation compared to individuals who have no such history (e.g., McGirr et al., 2010; Melhem et al., 2016; O'Connor et al., 2017). For example, McGirr et al. (2010) showed that a sample of first-degree relatives of individuals who had died by suicide exhibited a blunted (i.e., lower) cortisol response to stress compared to matched controls. Two more recent laboratory-based cortisol studies have also found evidence of blunted HPA axis activity in individuals with a history of suicide compared to controls (Melhem et al., 2016; O'Connor et al., 2017). Taken together the evidence is converging to indicate that the HPA axis, as indexed by cortisol reactivity to stress, is dysregulated in individuals vulnerable to suicide. Surprisingly, only limited research has examined relations between suicide risk and other components of HPA function, such as the cortisol awakening response (CAR). The CAR is defined as the rapid increase in cortisol levels following morning awakening (Clow et al., 2010) and has been found to be influenced by chronic stress, trauma and a range of other negative psychosocial variables – all factors frequently implicated in increased suicide risk (Boggero et al., 2017; Chida and Steptoe, 2009, Clow et al., 2010; Gartland et al., 2014; O'Connor et al., 2013; O’Connor et al., 2021).

One study that has investigated the association between suicide vulnerability and the CAR (as well as the diurnal cortisol slope) is a recent study by O'Connor et al. (2020a). The results showed that participants who had a history of suicide attempt or ideation had a significantly lower total CAR compared to control participants over 7 days. This study also found that childhood trauma was significantly associated with lower total CAR. The authors argue that these findings suggest that the experience of childhood trauma may predispose individuals to vulnerability to suicide in adulthood by leading to diminished HPA axis activity during awakening and during stress. A considerable body of research has accumulated to suggest that repeated activation of the HPA axis leads to dysregulation (Miller et al., 2007; McEwen, 1998; O'Connor et al., 2021). This is known as allostatic load (McEwen, 1998), whereby, if the HPA axis is repeatedly activated (e.g., by chronic stress or exposure to childhood trauma), the immune, cardiovascular and endocrine systems are potentially exposed to excessive demands that over time can lead to dysregulation of these systems (Miller et al., 2007; McEwen, 1998; O'Connor et al., 2021).

In the broader suicide literature, leading models such as the Integrated Motivational-Volitional Model (IMV; Branley-Bell et al., 2019; O'Connor, 2011, O’Connor and Kirtley, 2018) of suicidal behavior have identified numerous other psychological vulnerability factors (e.g., trait perfectionism, trait impulsivity, social support). For example, it is well established that levels of socially prescribed perfectionism – holding excessive beliefs and expectations that significant others have high standards for you – are often significantly higher in individuals who have previously attempted to end their own lives (Smith et al., 2018; O'Connor, 2007a, O'Connor et al., 2007b). Similarly, trait impulsivity has been found to be an important variable in helping to explain why some individuals are more likely to act on their suicidal thoughts and attempt suicide than other individuals (O’Connor and Nock, 2014). The absence of social support (i.e., social isolation) has also been implicated in numerous models and studies of suicidal behaviour (e.g., Haw and Hawton, 2011; O’Connor and Kirtley, 2018). However, how these more established vulnerability factors may be associated with HPA axis dysregulation, in particular the CAR, together with identifying resilience factors that may help protect against dysregulation, remains under researched.

The IMV model (O'Connor, 2011, O’Connor and Kirtley, 2018) of suicidal behavior provides a theoretical basis for examining the factors associated with the development of suicidal ideation and the transition from ideation to suicide attempts. It integrates predominant factors from existing psychosocial models including Williams' arrested flight model (Williams, 2001), the diathesis-stress hypothesis (Schotte and Clum, 1987), and the theory of planned behavior (Ajzen, 1991). The IMV model conceptualises suicide as a behavior that results from a complex interplay of factors; and provides a detailed map of the pathway from ideation to behavior, through defeat and entrapment (Branley-Bell et al., 2019). The diathesis-stress component of the IMV model recognizes that individual vulnerabilities confer elevated risk for developing suicidal ideation when activated by the presence of stressors. Examples of these vulnerabilities are personality characteristics, such as high socially prescribed perfectionism and socio-economic deprivation (O'Connor and Nock, 2014).

The IMV model proposes that the central predictor of a suicide attempt is an individual's intention to engage in suicidal behavior. Feelings of defeat/humiliation trigger feelings of entrapment, which in turn predicts intention (i.e., ideation) as an escape from intense psychological distress. Throughout this process, there are stage-specific moderators that facilitate or prevent progress to the next stage, with threat-to-self moderators (e.g., trait worry, rumination processes) and motivational moderators (e.g. trait resilience, social support) predicting ideation, and volitional moderators (e.g., trait impulsivity) governing enactment. As outlined earlier, relatively few, if any studies have explored the relationship between these key established vulnerability and resilience factors, and HPA axis functioning in naturalistic settings or have investigated in the same study whether this range of factors are different in suicide vulnerable individuals.

Using data from the recent O'Connor et al. (2020a) study that included individuals with a suicide risk history (suicide vulnerability group) alongside individuals with no suicide risk history (control group), the current investigation aimed:

• To test whether resilience factors' scores (trait resilience and social support) were lower and vulnerability factors' scores (trait worry, socially prescribed perfectionism, trait impulsivity) higher in individuals vulnerable to suicide compared to controls.

• To examine the effects of resilience and vulnerability factors on the cortisol awakening response in individuals vulnerable to suicide.

• To test whether there were indirect effects of suicide vulnerability group membership on cortisol awakening response via the resilience and vulnerability factors.