The cortisol awakening response: neuropsychological correlates and implications for function in healthy humans
In healthy individuals, cortisol secretory activity shows a marked circadian rhythm. This rhythm is characterised by a declining pattern across the day, reaching a nadir in the late evening and early part of sleep, before gradually increasing during late sleep to reach peak levels upon subsequent morning awakening. The focus of the present thesis is a distinct aspect of this circadian rhythm: the rapid increase in cortisol concentrations to reach the diurnal acrophase within the first 45 minutes after awakening, known as the cortisol awakening response (CAR). The CAR is a much studied but poorly understood aspect of the circadian pattern of cortisol secretion. Despite being considered a biomarker of health status in psychophysiological and neuroendocrine research, its precise function within the healthy cortisol circadian rhythm has yet to be elucidated, and results from CAR studies in clinical populations have often been inconsistent. The focus of this programme of research was to seek a role for the CAR in healthy functioning young adults, and to address methodological issues that may have contributed to the inconsistent and contradictory findings from earlier studies. The data presented here from healthy young adult participants demonstrate for the first time that the CAR predicts better performance on an index of executive function (EF) in the same day. This is first demonstrated in a detailed case study of a healthy young adult male, showing that state variation in the CAR predicts EF at 45-min post-awakening, and then in a sample of healthy young adults, demonstrating that CAR predicts EF in the afternoon of the same day. In a further study of healthy young adults, the magnitude of the CAR was found to positively predict the capacity to induce synaptic plasticity in the motor cortex on that same day by Transcranial Magnetic Stimulation (TMS). This study demonstrates, for the first time, that the daily magnitude of the CAR may be responsible for some daily variation in synaptic plasticity, presenting a possible mechanism by which the CAR might influence cognitive function. The unique contribution of this thesis lies in its progression from previous studies of elderly and clinical populations by demonstrating a possible role for the CAR in healthy young adults, as well as the detailed examination of state variation in the CAR and the use of strict methodologies to ensure accuracy of measurement. This has the potential to lead toward a clearer understanding of the role of the CAR within the healthy cortisol circadian cycle, and therefore the consequences of dysregulation in a range of conditions. The findings are discussed with regard to their contribution to understanding the relationship between the CAR and cognitive function, and the implications for methodology and interpretation of the broad range of studies using the CAR as a trait biomarker.
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