Adrenocortical Functioning in Boys with Attention-Deficit/Hyperactivity Disorder: Examining Subtypes of ADHD and Associated Comorbid Conditions

Abstract

Disruptions to hypothalamic-pituitary-adrenal (HPA) axis function have been associated with varying forms of psychopathology in children. Studies suggesting children with ADHD have blunted HPA function have been complicated by the prevalence of comorbid diagnoses and heterogeneity of ADHD. The goals of this research were to assess the relations between waking and stress-response salivary cortisol levels and comorbid disruptive behavior (DBD) and anxiety (AnxD) disorders and problems in boys with ADHD, and to examine whether cortisol levels varied across ADHD subtypes. One hundred seventy elementary school-age boys with ADHD provided salivary cortisol at waking and in reaction to venipuncture. Parent reports were used to assess boys' psychiatric diagnoses and severity of behavioral problems. Boys' comorbid AnxD and anxiety problems were associated with greater cortisol reactivity, whereas boys' comorbid DBD and oppositional problems predicted diminished adrenocortical activity. Reactive cortisol increases were greatest in boys with ADHD and comorbid AnxD, but without DBD. ADHD subtypes were not differentially associated with waking, pre-stress baseline, or reactive cortisol levels. However, comorbid DBD predicted decreased cortisol reactivity in boys with inattentive and hyperactive subtypes of ADHD, but not in boys with combined subtype of ADHD. The results clarify previous patterns of distinct and divergent dysregulations of HPA function associated with boys' varying kinds of psychopathology.

Altered circadian profiles in attention-deficit/hyperactivity disorder: An integrative review and theoretical framework for future studies

“…Some authors confirmed a hypo-arousal pattern in children with ADHD+ODD measuring both awakening (Freitag et al, 2009) and basal values (Kariyawasam et al, 2002) while other authors failed to find any robust association between waking levels and comorbid problems in ADHD (Hastings et al, 2009). In line with these findings, no differences in basal levels between ADHD children with aggression and without aggression have been reported (Schulz et al, 1997), suggesting the possibility that certain characteristics of ADHD, rather than aggression, could be associated with cortisol levels.…”

Genetic Evidence for the Association of the Hypothalamic–Pituitary–Adrenal (HPA) Axis with ADHD and Methylphenidate Treatment Response

“…Cortisol then acts on the hypothalamus, pituitary, and hippocampus to inhibit its own production in a negative feedback loop. It has been reported that children with ADHD have a blunted cortisol response to psychosocial stressors, a decreased cortisol awakening response (CAR), or lower plasma daytime cortisol (King et al 1998;Ma et al 2011;Randazzo et al 2008;Scerbo and Kolko 1994;van West et al 2009), though there is considerable inconsistency between studies (Freitag et al 2009;Hastings et al 2009;Snoek et al 2004).…”

Endocrine Dysfunction and Growth in Attention Deficit Hyperactivity Disorder

“…Diminished wakening cortisol was not observed in children with ADHD only or in children with ADHD plus conduct disorder or anxiety disorder (Freitag et al, 2009). In other studies, in this case 170 elementary school-age ADHD males, no differences in baseline, waking cortisol levels between ADHD subtypes could be demonstrated (Hastings et al, 2009). …”

“…increased stressed cortisol levels in response to venipuncture are greater in some ADHD children with coexisting anxiety disorders than in those with comorbid disruptive behavior or oppositional problems (Hastings et al, 2009).…”

“…In summary, studies of hypothalamic -pituitary -adrenocortical axis activity in ADHD children have yielded conflicting results, likely due to the confounding variables of comorbidities, subtypes and heterogeneity of ADHD (Hastings et al, 2009); the variety of methods used to assess stress hormone activity; and current psychosocial conflicts such as parenting issues, family conflicts and stressful, acute life events, all of which can increase cortisol levels (Freitag et al, 2009) and affect the outcome of studies of hormonal levels and behavior. If further research is able to better clarify this complex interaction, measurements of hormonal levels may become a useful diagnostic adjunct to help select the most appropriate treatment modalities for pediatric behavioral disorders and aggression (Barzman et al, 2010 Abbreviations: ADHD = attention deficit hyperactivity disorder; ADHD-CU = ADHD with callous unemotional traits; ADHD-HI = ADHD with hyperactive impulsive traits; ADHD-I = ADHDpredominantly inattention type; ADHD-C = ADHD-combined type Table 1.…”