ADHD-related behavioural symptoms have been proposed to be associated with deficits of arousal or the ability to maintain optimal levels of arousal (Sonuga-Barke et al., 2010). Indeed, ADHD patients also suffer from sleep disturbances (Cortese et al., 2009), excessive daytime sleepiness (Lecendreux et al., 2000), afternoon increased hyperactivity (Antrop et al., 2002), and circadian heart rate changes with a trend toward high heart levels at specific times throughout the day (Imeraj et al., 2011). Arousal has been associated with the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and cortisol is the main representative of the activity of this axis (Garde et al., 2011). Cortisol is involved in a wide range of cognitive functions including focused attention, sustained effort and effortful thought (M.F. Dallman, 1993; Schulkin, 1999); all of these functions are difficult for patients with ADHD.
Cortisol levels and their associations with physiological, cognitive and behavioural effects appear to be organized according to an inverted U-shaped curve in which medium cortisol levels are optimal, and high and low cortisol levels have adverse effects on behaviour and cognition and cause physiologically related issues (Beckwith et al., 1986; Lupien et al., 1997).
Cortisol awakening response (CAR) has been studied in children with ADHD, and some authors have reported blunted CARs in these patients as well as morning cortisol differences among ADHD subtypes. Only half of the children with ADHD continue to exhibit the disorder into adulthood. Nevertheless, CAR has not been studied in adults with ADHD.
Our group published this year the first study to assess the subtype differences in the CAR in adults with ADHD (Ramos-Quiroga et al., 2016). This study also aimed to investigate the possible association between the cortisol response at awakening and the core deficits that characterize ADHD, i.e., inattention, hyperactivity and emotional lability and to assess the differences between the inattentive and combined subtypes. We studied a sample of one hundred and nine adults with ADHD according to the DSM-IV criteria (46 inattentive and 63 combined) and ranging in age from 18 to 55 years old and 27 healthy controls.
Samples of salivary cortisol were obtained from every subject at 0, 30, 45 and 60 minutes after awakening. CAR was present in 84% of the healthy controls but in only 64% of the adults with ADHD (68% of the inattentive ADHD patients and 61% of the combined ADHD patients were CAR-positive). There were no significant differences in any of the morning cortisol measures between the ADHD patients and the healthy controls or between the combined and inattentive subtypes of ADHD. Significant positive correlations were observed between the CAR and the emotional lability and self-concept subscales of Conners Adult ADHD Rating Scale (CAARS) among the inattentive subtype but not the combined patients. It is important to mention that all of the patients were naïve to stimulant medications, and none of them had comorbid psychiatric or organic disorders. These results are in line with those of a previous study performed in our department that assessed basal cortisol levels in the afternoon and identified no group differences in basal cortisol at 2:00 PM (Corominas et al., 2015). These results suggest that adults with ADHD exhibit normal cortisol responses upon awakening and thus cannot be defined in terms of hypo-arousal. Nevertheless, some differences in the neurobiological profiles involving cortisol appear to underlie the combined and inattentive subtypes.
In summary, no differences between the patients and controls or between the inattentive and combined subtypes of adult ADHD were observed in the cortisol levels upon awakening, suggesting that the HPA axis is not directly associated with the deficits that characterize these patients. These results suggest that adults with ADHD cannot be defined in terms of hypo-arousal. However, there were some profile differences between the inattentive and combined subtypes of adults with ADHD. Whereas the inattentive adults exhibited positive relationships of cortisol level upon awakening with emotional lability and difficulties with self-concept, these relationships were not present in the combined adults, suggesting neurobiological differences between the subtypes.