BDNF and Cortisol Levels in Children with ADHD - A Study of Biological Factors and the Effects of Methylphenidate Treatment

Public defence of PhD thesis by Maj-Brit Åström.

 

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder linked to substantial impairment. To improve understanding of neurobiological mechanisms and treatment effects, this PhD project examined two biological factors involved in neuroplasticity and stress regulation: Brain-Derived Neurotrophic Factor (BDNF) and cortisol. A prospective 12-week cohort study was conducted in psychostimulant-naïve children with ADHD (7–12 years) and matched controls, assessing plasma BDNF and salivary cortisol profiles before and after individually titrated methylphenidate (MPH) treatment. In addition, a systematic review synthesized evidence on hypothalamus–pituitary–adrenal (HPA) axis alterations in prepubertal ADHD.

Children with ADHD showed consistently higher plasma BDNF levels than controls, and higher baseline BDNF predicted greater clinical improvement following MPH, suggesting that stronger neurotrophic capacity may facilitate treatment response.

Cortisol analyses indicated comparable baseline profiles, while MPH treatment was associated with a dose-dependent increase in the cortisol awakening response and impaired post-stress recovery after repeated venipuncture, indicating enhanced HPA-axis activation without normalization of post-stress downregulation.

The systematic review identified substantial heterogeneity in cortisol findings, suggesting that observed differences in HPA-axis function may depend on subtype, comorbidities, and methodological variation, rather than reflecting a uniform pattern of dysregulation in ADHD.

Overall, the findings indicate that BDNF and cortisol reflect distinct yet interconnected biological processes that may be involved in the pathophysiology of ADHD. Alterations in both systems and evidence of MPH-related change support ADHD as involving heterogeneous biological mechanisms requiring longitudinal and methodologically consistent investigation.

 

Assessment committee

  • Professor Kamilla Miskowiak, Deptartment of Psychology, University of Copenhagen, Denmark (chair)

  • Clinical Associate Professor Simon Hjerrild, Department of Clinical Medicine, University of Aarhus, Denmark

  • Associate Professor Max Karukivi, Unit of Adolescent Psychiatry, Satakunta Hospital District, Finland

Supervisors

  • Professor Thomas Habekost, Department of Psychology, University of Copenhagen, Denmark (principal supervisor)

  • Professor Signe Vangkilde, Department of Psychology, University of Copenhagen, Denmark (co-supervisor)

  • Professor Kerstin J. Plessen, Department of Psychiatry, Lausanne University Hospital, Switzerland (co-supervisor)