Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis

Abstract

Background: Cognitive impairment, particularly in memory and executive function, is a core feature of psychosis. Moreover, psychosis is characterized by a more prominent history of stress exposure, and by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. In turn, stress exposure and abnormal levels of the main HPA axis hormone cortisol are associated with cognitive impairments in a variety of clinical and experimental samples; however, this association has never been examined in first-episode psychosis (FEP).

Method: In this study, 30 FEP patients and 26 controls completed assessment of the HPA axis (cortisol awakening response and cortisol levels during the day), perceived stress, recent life events, history of childhood trauma, and cognitive function. The neuropsychological battery comprised general cognitive function, verbal and non-verbal memory, executive function, perception, visuospatial abilities, processing speed, and general knowledge.

Results: Patients performed significantly worse on all cognitive domains compared to controls. In patients only, a more blunted cortisol awakening response (that is, more abnormal) was associated with a more severe deficit in verbal memory and processing speed. In controls only, higher levels of perceived stress and more recent life events were associated with a worse performance in executive function and perception and visuospatial abilities.

Conclusions: These data support a role for the HPA axis, as measured by cortisol awakening response, in modulating cognitive function in patients with psychosis; however, this association does not seem to be related to the increased exposure to psychosocial stressors described in these patients.

Fig. 1

Scatter plot and linear regression of cortisol awakening response and z scores of (a) verbal memory and (b) processing speed domains, in patients. Significant positive correlations were observed for both verbal memory (r=0.48, p=0.019) and processing speed (r=0.38, p=0.048).

Fig. 2

Z scores (means and standard deviations) of the individual cognitive domains in subjects divided into (a) those below and above the median of the cortisol awakening response and (b) those below and above the median of cortisol secretion during the day. The individual cognitive tests were grouped into six domains: Verbal memory; Non-verbal memory; Executive function perception; Visuospatial abilities; and Processing speed. Scores on each cognitive domain were calculated as the mean of standard (z) scores of the individual tests. Z scores were based on the mean and standard deviation of the control sample. (a) Within patients, the group with the cortisol awakening response below the median (i.e. more blunted and hence more abnormal) did worse on all cognitive domain, reaching statistical significance for verbal memory and processing speed, and trend significance for perception and visuospatial abilities. No differences were observed between controls with a high and with a low cortisol awakening response in any cognitive domains. (b) No differences were found in cognitive function between subjects with low and high cortisol levels during the day, in either patients or controls. * p<0.05.