واکنش به استرس در کودکان و نوجوانان برزیلی با اختلال نقص توجه و بیش فعالی

This study assessed the function of the hypothalamic–pituitary–adrenal (HPA) axis, during response to stress, through the measurement of salivary cortisol in 38 children with attention deficit hyperactivity disorder (ADHD) and its subtypes, who were matched to 38 healthy control subjects. These measures were made at four time intervals: 15 min before exposing the subjects to a stressor — the Continuous Performance Test (CPT) – and 20, 40, and 60 min after such exposure. The baseline cortisol levels were statistically similar in both groups. The mean values of cortisol at the four time intervals were not statistically different between the three subtypes of ADHD (inattentive, hyperactive–impulsive and combined); thus, the ADHD group was treated as a single group. Following the stressor test, the ADHD group had significantly higher levels of salivary cortisol than the control group at time intervals of 20 and 40 min, whereas in this latter group exposure to the CPT did not induce an increase of cortisol. These results suggest that the increased cortisol levels in the ADHD group could be due to the lack of comorbidities. In addition, these patients, when facing a computerized test, might have responded with a motivational pathway with an increase of cortisol.

Attention deficit hyperactivity disorder (ADHD) is the most common of the emotional, cognitive and childhood behavior disorders (Wilens and Dodson, 2004). It is multifactorial and clinically heterogeneous (Biederman, 2005), with a prevalence rate of 5–8% in school–aged children (Freitag et al., 2009). Data are scarce for ADHD prevalence rates in Brazilian children; however, Rohde et al. (1999) found a rate of 5.8% in a sample of Brazilian adolescent students. ADHD affects more boys than girls, with ratios varying from 2:1 to 10:1 (FontanaI et al., 2007). According to the criteria outlined in the DSM IV-TR (2000), the cardinal symptoms of ADHD are poor concentration, hyperactivity and impulsiveness; leading to its division into the following three subtypes: inattentive, hyperactive–impulsive and combined. These symptoms must be accompanied by impairments in social interactions, academics, quality of life, and the cognitive and emotional development of the individual. Often, the behavior of very young children with ADHD goes unnoticed by their parents; however, when they go to school, even mild cases tend to become evident. This is probably because the school environment provides an opportunity to compare children of the same age, and children are required to pay more attention and need to remain in one place for longer periods than they had to do at home (Rohde and Mattos, 2003). ADHD is associated with a high rate of psychiatric comorbidity, particularly oppositional defiant disorder, conduct disorder, mood and anxiety disorders, smoking and drug abuse (Wilens and Dodson, 2004). The social cost of untreated ADHD is considerable and includes low academic achievement, behavioral problems, underemployment, car accidents, and relationship problems (Barkley et al., 1993, Biederman et al., 2000 and Matza et al., 2005). Several theoretical models have been formulated in an attempt to understand the mechanisms involved in the etiology of ADHD. Barkley (1997) tried to unify the major ethiological theories based on the neuropsychological functions of the pre-frontal lobes and proposed “response inhibition”, a function enabling an individual to delay a determined response to an immediate environmental event, would be impaired in individuals with ADHD. It could then result in a series of secondary deficits, such as difficulty in concentration and errors by precipitation (Barkley, 2006). Subsequently, neuroimaging studies have demonstrated a delay of cerebral maturation, mainly in the frontal lobe (Shaw et al., 2007 and Shaw et al., 2011). In fact the executive functions include complex mental activities which are needed to plan, organize, guide, review and monitor behavior required to achieve goals. Such functions begin to develop during the first year of life and continue their development until adolescence; however, these functions seem impaired in patients with ADHD (Barkley, 1998). Furthermore, if one core deficit of ADHD is a dysfunctional behavioral inhibition system, an abnormality of the hypothalamic–pituitary–adrenal (HPA) axis might be expected in patients with ADHD. A low reactivity of the HPA axis to stress in patients with ADHD has been associated with their poor performance. Patients with ADHD who retained their diagnosis for more than 1 year showed a blunted response to stress when compared with an ADHD group that no longer met diagnostic criterial (Hong et al., 2003 and King et al., 1998). A recent study of prepubertal children with ADHD subtypes and a healthy control group found that children with inattentive ADHD had an elevated cortisol response to a psychosocial stressor, in contrast to children with combined ADHD who had a blunted cortisol response. The authors suggest that a low-cortisol responsivity to stress might be a neurobiological marker for children with ADHD (van West et al., 2009). Other studies have not found an association between reduced cortisol concentrations and ADHD. Kaneko et al. (1993) reported that only those with severe and moderate hyperactivity had an increase of cortisol after exposure to stress. Kariyawasam et al. (2002) found lower cortisol levels in 32 children with comorbid ADHD and opposition defiant disorder (ODD); a finding that was restricted to the subgroup of unmedicated patients. Hong et al. (2003) found two different cortisol reactivity patterns during a stress test in patients with ADHD: one group had increased cortisol levels whereas the other one had decreased cortisol levels. Snoek et al. (2004) found normal reactivity to stress in individuals with ADHD. Shirtcliff et al. (2005) reviewed the relationship between cortisol levels and internalized and externalized behavioral problems, concluding that only boys with higher levels of externalizing problem behaviors had low cortisol levels. Although findings concerning cortisol response to stress were inconsistent in early studies, recent research with larger samples or better methodology has not provided convincing evidence of cortisol changes in non-comorbid forms of ADHD. Several of these studies have not examined the differences of cortisol's reactivity in the three sub-types of ADHD as specified by the DSM IV-TR. Therefore, it is not clear whether the cortisol decrease in response to a stressor is a characteristic of the ADHD diagnosis or of one of its subtypes (Randazzo et al., 2008). It is important to emphasize that until the last decade, knowledge about the function of the HPA axis was limited to research in animals and human adults. The lack of research in children and adolescents was likely because of the invasive techniques needed to obtain cortisol samples. Currently, the high sensitivity of the immunoassay to measure salivary cortisol, given the significant correlation between free salivary and total plasma cortisol levels in both adults and children, facilitated these studies in young samples (Kahn et al., 1988, Klimes-Dougan et al., 2001 and Raff et al., 1998). Furthermore, most previous studies have important differences in their methodological designs, such as sampling, diagnostic assessments, repeated cortisol measures, and stressors (Lackschewitz et al., 2008 and Randazzo et al., 2008). Another major limitation has been the lack of assessment of comorbid disorders. Thus, we decided to study a sample of ADHD without psychiatric comorbidities. These study objectives were: a) to investigate difference of cortisol reactivity to stress in ADHD subtypes; b) to compare the ADHD group with healthy controls.