Attenuated cortisol response to acute psychosocial stress in individuals at ultra-high risk for psychosis

Abstract

We recently reported that individuals at ultra-high risk for the development of psychosis (UHR) have elevated levels of chronic stress and deficits in the putative protective factors self-esteem, social support and coping skills. The aim of the present study was to assess endocrine and autonomic responses to acute psychosocial stress and their associations with self-ratings of stress and protective factors in individuals at UHR.

Twenty-one patients diagnosed with an “at risk mental state” (12 male, 9 female; mean age 20.8 ± 3.27) and 21 healthy age and gender matched community controls were exposed to the Trier Social Stress Test (TSST). Saliva samples for cortisol assessment and measurements of heart rate and blood pressure were taken throughout the testing period. Levels of perceived chronic stress, protective factors and depression were assessed with reference to the preceding month and year (stress only).

Compared to healthy controls, individuals at UHR reported significantly higher levels of depression, deficits in protective factors, and a trend for higher chronic stress levels. Cortisol levels and systolic blood pressure during the TSST were significantly lower in the UHR group, while heart rate changes were comparable to controls. Lower cortisol levels in the UHR group were associated with higher self-ratings of stress in the past year and a lower level of education. Attenuated cortisol responses to acute psychosocial stress in the presence of high chronic stress could indicate a desensitization of the HPA axis. Associated poor metabolic and psychological adjustment to stress might increase vulnerability for the development of psychosis.

Introduction

Chronic or cumulative exposure to psychosocial stress is considered an important factor implicated in the pathophysiology of schizophrenia (Phillips et al., 2007, van Winkel et al., 2008). In a recent study, we reported elevated levels of perceived chronic stress in individuals at ultra-high risk for the development of psychosis (UHR) (Pruessner et al., 2011). In accordance with this finding, two other recent studies reported greater distress and negative emotions in response to life events and daily hassles in people at UHR compared to healthy controls (Palmier-Claus et al., 2011, Phillips et al., 2011). These findings supplement previous reports of high emotional reactivity to daily events in first-degree relatives of patients with psychosis (Myin-Germeys et al., 2001) and of more undesirable life events and more distress in response to daily hassles in adolescents with schizotypal personality disorder (SPD) (Tessner et al., 2011). In general, rather than being exposed to a higher number of stressful events, high-risk individuals might perceive events as more stressful than healthy controls (Phillips et al., 2007), a conclusion that has also been drawn for patients with established psychosis (Norman and Malla, 1993a, Norman and Malla, 1993b). Such vulnerability to stress is probably determined largely by the interaction of a person's genetic make-up and the consequences of previous life stressors (Zubin and Spring, 1977). In addition, the subjective experience of stress and its long-term health impact are likely to be influenced by the availability of certain protective factors. For example, patients at high risk for psychosis exhibit deficits in coping skills, social support and self-esteem (Phillips et al., 2011, Pruessner et al., 2011), and both high stress levels and deficits in protective factors can predict symptom severity in the high risk phase (Tessner et al., 2011, Palmier-Claus et al., 2011, Pruessner et al., 2011).

The two major physiological systems responding to stress are the sympathetic nervous system (SNS) and the hypothalamus–pituitary–adrenal (HPA) axis, which set into motion various processes to ensure adaptation to metabolic and behavioral needs in stressful situations (de Kloet et al., 2005, Chrousos, 2009). Neural diathesis stress models propose the endocrine stress system as a likely mediator between the experience of stress and the onset or exacerbation of psychotic symptoms (Walker and Diforio, 1997, Corcoran et al., 2003). Acute stress normally leads to cortisol increase, but animal and human studies have shown that cumulative or chronic exposure to stress can cause pathological alterations in the regulation of the hypothalamus–pituitary–adrenal (HPA) axis with various consequences for subsequent function of the axis and related health outcomes (Heim et al., 2000, McEwen, 2008). In psychosis, elevated cortisol levels are believed to cause alterations in dopamine regulation resulting in psychotic symptoms (Walker and Diforio, 1997). Evidence for a dysregulation of the HPA axis in patients with established psychosis comes from studies reporting elevated baseline cortisol levels (Ryan et al., 2004, Gallagher et al., 2007) and non-suppression to dexamethasone challenge (Muck-Seler et al., 1999). In contrast to these reports of hypercortisolism at baseline, evidence points to lower than normal cortisol levels in patients when the reactivity of the HPA axis is tested, with an attenuated cortisol response to awakening (Pruessner et al., 2008, Mondelli et al., 2009, Pruessner et al., 2013) and in response to acute psychosocial stress (Jansen et al., 1998, Jansen et al., 2000, Brenner et al., 2009, Steen et al., 2011).

Several studies also provide evidence for abnormal HPA regulation in people at elevated risk for psychosis. Compared to healthy controls, patients with schizotypal personality disorder showed higher salivary cortisol levels at baseline (average of three samples taken between 9 and 11 am) (Walker et al., 2001, Mittal et al., 2007), and individuals who subsequently converted to psychosis displayed increased cortisol secretion at initial assessment (Walker et al., 2010). Furthermore, in individuals at high risk for psychosis, the experience of more hassles was associated with a higher cortisol response at 8 am. Similarly, siblings of patients with psychosis presented with higher diurnal cortisol levels and higher cortisol reactivity to negative daily events (Collip et al., 2011). Whereas increased cortisol levels were related to the severity of psychotic like experiences in some studies (Walker et al., 2001, Collip et al., 2011), another study did not find such an association (Thompson et al., 2007b).

No study to date has assessed the cortisol response to acute psychosocial stress in individuals at UHR for psychosis. Our aims for the present study were (1) to compare the cortisol response to an established psychosocial stress task in individuals at clinically high risk for psychosis and healthy controls and (2) to assess the relationship of this endocrine measure with subjective measures of acute and chronic stress and with protective factors. Based on our previous findings in UHR patients and literature regarding patients with clinically confirmed psychosis, we hypothesized higher stress levels, lower ratings on protective factors, and an attenuated cortisol response to a psychosocial stress task in the UHR group compared to healthy controls.