A lifetime of attention-deficit/hyperactivity disorder: diagnostic challenges, treatment and neurobiological mechanisms

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and enduring neuropsychiatric disorder characterized by developmentally inappropriate deficits in attention, hyperactivity, increased impulsivity and emotional dysregulation, resulting in impairments in multiple domains of personal and professional life. ADHD has long been considered a disorder of childhood that resolves gradually with maturation during adolescence; however, this view was contested by systematic follow-up studies documenting the persistence of ADHD across the lifespan. In this article, we present converging evidence from clinical and genetic studies arguing for a remarkable perseverance of ADHD-related symptomatology, taking into account the disorder’s variable and changing phenotype moderated by a high rate of comorbidity throughout the lifecycle. We also cover findings highlighting alterations in structural and functional neuroanatomy based on neuropsychological, psychophysiological and brain imaging approaches, and discuss options for deficit-focused pharmacological and psychotherapeutic interventions at different stages of life. In addition, we develop a fusion model of disease risk underlying the pathway to ADHD etiology. Finally, we argue for large-scale, systematic studies to explore factors predicting the long-term outcome of the disease and the possibilities to exploit those predictors with more personalized treatment strategies to enhance remittance and/or coping.

Keywords::

• ADHD
• adult
• amphetamines
• atomoxetine
• brain imaging
• childhood
• cognitive–behavioral therapy
• genetics
• methylphenidate
• pharmacotherapy
• structural and functional neuroanatomy

Acknowledgements

The authors thank all members of the International Multicentre Persistent ADHD Collaboration (IMpACT) Consortium (Barbara Franke, Stephen V Faraone, Claiton Bau, Josep A Ramos-Quiroga, Bru Cormand, Eric Mick, Stefan Johansson, Jan Haavik, Jan Buitelaar and Philip Asherson) for inspiration and helpful discussion.

Financial & competing interests disclosure

The work of the authors is supported by the Deutsche Forschungsgemeinschaft (KFO 125, GRK 1253) and the Bundesministerium für Bildung und Forschung (BMBF 01GV0605). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.