Long-term cortisol secretion in attention deficit hyperactivity disorder: roles of sex, comorbidity, and symptom presentation

Abstract

Low activity of the hypothalamic–pituitary–adrenal axis (HPAA) has been found in children with attention deficit hyperactivity disorder (ADHD). The condition may be related to the reduced attention regulation capacity and/or to comorbid oppositional defiant or conduct disorder (ODD/CD). Sex differences are probable but not sufficiently studied. We analyzed the HPAA activity and sympathetic nervous system reactivity (SR) in children with ADHD while accounting for ADHD symptom presentation, comorbidity, and sex differences. The sample comprised 205 children, 98 (61 boys, 37 girls) with ADHD and 107 (48 boys, 59 girls) healthy controls. DSM-5 phenotypic symptom presentation and comorbid ODD/CD were assessed using clinical interviews. Hair cortisol concentration (HCC) was used to assess the long-term, cumulative activity of the HPAA. SR was assessed via skin conductance response (SCR). For control purposes, comorbid internalizing symptoms and indicators of adverse childhood experiences (ACE) were assessed. Children were medication naive. Boys presenting with predominantly inattentive symptoms (ADHD-I) showed lower HCC than healthy boys. Girls presenting with combined symptoms (ADHD-C) showed higher HCC than did healthy girls (p’s < 0.05, sex-by-group interaction, F (2,194) = 4.09, p = 0.018). Boys with ADHD plus ODD/CD showed a blunted SR (p < 0.001, sex-by-group interaction, F (2,172) = 3.08, p = 0.048). Adjustment for ACE indicators led to non-significant differences in HCC but did not affect differences in SR. HCC constitutes an easily assessable, reliable, and valid marker of phenotypic ADHD-related features (i.e. symptom presentation and comorbidity). It indicates more homogenous subgroups of ADHD and might point to specifically involved pathophysiological processes.

Relationship between hair cortisol concentrations and cognitive functioning in adolescents with ADHD

“…In this sense, it is essential that clinicians obtain a maltreatment history when assessing or treating individuals with ADHD, and the CTQ could be an easy instrument for assessment. As maltreatment is such a strong risk factor for mental disorders, there should be an effort to reduce exposure and to develop strategies to prevent the development of psychiatric disorders in exposed youth (Pauli-Pott et al, 2023 ). This recommendation would also be extrapolated to the importance of obtaining HPA axis measures, and given the plasticity of HCCs in response to targeted interventions, establishing interventions (Blaisdell et al, 2019 ; Fisher & Stoolmiller, 2008 ).…”

“…However, substantial heterogeneity has been found in the effects reported by individual studies (Scassellati et al, 2012 ). Potential moderating variables need to be considered when exploring the role of the HPA axis in ADHD, such as sex differences, symptom presentation and environmental conditions, which can explain the heterogeneity observed (Pauli-Pott et al, 2023 ).…”

“…Moreover, there are considerable sex differences in this symptomatic presentation and in prevalence rates (Hinshaw et al, 2022 ). Given that HPA axis function differs between sexes, shows heritability by adjusting to environmental conditions and is related to neurocognitive and emotional functions, a nonuniform pattern of HPA axis dysregulation is likely to be found in children and adolescents with ADHD (Pauli-Pott et al, 2023 ).…”

“…Although psychosocial risk was assessed in this previous study, potential interactions between childhood maltreatment and HPA axis measures were not considered. Later studies by the same research group suggested that it would be particularly valuable to consider maltreatment as a potential moderator of this association (Pauli-Pott et al, 2023 ). In the same way, previous research by our group provided support for childhood maltreatment as a moderator of the relationship between HPA axis measures and cognition in individuals with ADHD (Llorens et al, 2022 ).…”

Adult ADHD: It is Old and New at the same time. What is it?

“…hypothalamuspituitary-adrenal (HPA) axis. Though not comprehensively studied, factors such as suppressed HPA axis induce low cortisol levels, especially in the hyperactive-impulsive ADHD presentation [54,55]. Moreover, the thyroid hormones regulated by the HPA axis were dysregulated in ADHD [56,57], particularly those with hypothyroidism and generalized resistance to thyroid hormone (GRTH).…”