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'Integrative Neuroscience' Perspective on ADHD

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'Integrative Neuroscience' Perspective on ADHD THeMED ArTICLe y ADHD Review For reprint orders, please contact [email protected] An ‘integrative neuroscience’ perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support Expert Rev. Neurother. 10(10), 1607–1621 (2010) Leanne M Williams†1,2, There remains a translational gap between research findings and their implementation in clinical Tracey W Tsang2, practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major Simon Clarke2,3 and disorders of brain health in childhood, adolescence and adulthood. Research studies have identified Michael Kohn2,3 potential ‘markers’ to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking 1BRAINnet; Brain Research and functions, such as sustaining attention and associated electrical brain activity, show promise in Integrative Neuroscience Network, CA, USA complementing the clinical management process. Emerging evidence highlights the relevance of 2Brain Dynamics Center, University of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience Sydney Medical School and Westmead framework for ADHD that offers one means to bring together cognitive measures of thinking Millennium Institute, Sydney, Australia functions with measures of emotion, and their brain and genetic correlates. Understanding these 3Center for Research into Adolescents’ Health, The Children’s Hospital at measures and the relationships between them is a first step towards the development of tools that Westmead, Sydney, Australia will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices. †Author for correspondence: Brain Dynamics Center, University of Keywords: attention-deficit/hyperactivity disorder • brain • BRAINnet • clinical decision support • cognition Sydney Medical School and Westmead • emotion • genetics • integrative neuroscience• nonstimulants • stimulants Millennium Institute, Sydney, NSW 2145, Australia [email protected] There is a ‘translational’ gap between research and chronic health condition affecting school- findings and their implementation in clinical aged children. It has been described as ‘a serious practice that applies to disorders of brain health disability with long-term consequences’. It has across the lifespan. Here, the focus is on atten- severe consequences in social, individual and tion-deficit/hyperactivity disorder (ADHD), as family settings, often resulting in financial costs the most common disorder of childhood/adoles- of treatment, psychological implications due to cence. Research studies have identified potential familial stress and breakdown, difficulties in aca- ‘markers’ for supporting diagnostic, functional demic and vocational areas, and increased risk of assessment and treatment decisions in ADHD. drug abuse [1]. Integrating findings from the current knowl- Using the Diagnostic and Statistical Manual of edge base on these markers is a first step towards Mental Disorders – Fourth Edition (DSM-IV) achieving consensus on how they are best used criteria, diagnosis of ADHD is currently founded clinically. We outline an integrative neurosci- on a classical triad of symptoms: inattention, ence framework for linking findings from cogni- hyperactivity and impulsivity [2]. �������������ADHD is typi- tive behavioral, emotion-related, brain and gene cally identified in childhood to early adolescence. measures, and their application to diagnosis, It persists into adulthood in 50–60% of cases. comorbidity and treatment in ADHD. Attention-deficit/hyperactivity disorder is a heterogeneous condition that carries a high Clinical picture of ADHD: past, present risk of comorbidity [3]. Conditions frequently & future comorbid with ADHD may be broadly classified Attention-deficit/hyperactivity disorder is consid- into three categories: learning problems, exter- ered to be the most common neuro developmental nalizing disorders (e.g., conduct disorder) and www.expert-reviews.com 10.1586/ERN.10.140 © 2010 Expert Reviews Ltd ISSN 1473-7175 1607 Review Williams, Tsang, Clarke & Kohn internalizing disorders (e.g., anxiety and depression). ADHD Ob�ective measures will enhance the reliability of clinical decisions, is more prevalent in males, although under-reporting in females and provide concrete benchmarks for monitoring progress. These may contribute to this difference [3]. benchmarks offer the additional benefit of engaging both patient and family, and providing them with explicit feedback [11]. In other The past: diagnostic origins of ADHD areas of medicine the use of quantitative measurements is already The diagnostic origin of ADHD can be traced back to the 1950s a matter of course in making diagnostic and treatment decisions. when it was termed ‘minimal brain dysfunction’. Subsequently, We expect to have stress tests to evaluate our cardiac function, the diagnostic labels of hyperactive syndrome, hyperkinesis, and high- and low-density lipoprotein cholesterol are commonly hyperactivity disorder of childhood and variations of ‘attention- used as markers for atherosclerosis treatment in cardiac disease [12]. deficit disorder’ were used. These changes reflect the evolution Towards this goal, theories of ADHD have seen an evolution in understanding the cause and defining criteria for ADHD [4]. from those focused on cognitive concepts to those focused on Despite these changes, there has been consistency in presuming brain systems or genetic susceptibility. A framework to integrate an underlying brain disturbance in this condition. these theories offers one way forward to link levels of organiza- tion – from genes to brain, cognition and clinical symptoms – in The present: DSM-IV the understanding of ADHD. The DSM-IV has based the diagnosis of ADHD on two symp- tom dimensions: inattention and hyperactivity/impulsivity. Each Exemplar approach: an ‘integrative neuroscience’ dimension is defined by nine criteria. Meeting six or more of these for ADHD criteria on either dimension is needed for a positive diagnosis of An essential commonality in theories of ADHD is the empha- ADHD ‘inattentive subtype’ or ADHD ‘hyperactive/impulsive sis on disturbances in core domains of function. The focus has subtype’. Meeting six or more on both dimensions yields a diagnosis particularly been on the domain referred to here as ‘thinking’. of ADHD with ‘combined subtype’. Symptoms must also present The term ‘thinking’ is used as a straightforward descriptive term before the age of 7 years, in two or more settings, causing social and that is an umbrella for behavioral, psychophysiological and brain academic problems without a primary cause in anxiety or stress [5]. imaging measures of general cognitive processes. More recent A generally similar pattern has been observed in adult samples [6]. evidence highlights associated disturbances in domains referred The DSM-IV has given explicit recognition to the hetero geneity to here as emotion, feeling and self-regulation. While different of symptoms. For example, the situation-specific nature of symp- terminology has been used to describe these domains in different toms is considered. However, it does have a systematic way of theories, there is a fundamental commonality in the constructs. defining ADHD as a broader spectrum with comorbid conditions For instance, the phrase ‘affect–motivation–arousal’ has been (internalizing and externalizing), within an integrative construct. used to refer to motivationally directed emotion processing and the lack of regulation of such processing in ADHD [13]. The future: beyond DSM-IV Although a consensus is emerging that ADHD is character- The DSM-IV,������������������������������������������� following its predecessors, relies on sub�ective������������� clini- ized by disturbances across the spectrum of emotion, thinking, cal assessment to classify behavior. In this regard, there may not feeling and self-regulation [14], no similar theoretical consensus always be a direct match between the ‘round hole’ of diagnos- exists regarding their cause and underlying brain–gene basis. tic signs and symptoms and the ‘square pegs’ of the brain–gene An ‘integrative neuroscience’ approach provides a framework to mechanisms underlying the pathophysiology of ADHD. draw together theories that emphasize the involvement of mul- The focus on ‘signs and symptoms’ has provided a pragmatic tiple and dynamic brain pathways in the development of ADHD. and consistent nomenclature across clinicians. Rapidly emerging Such a framework will assist in the methodological identification findings for the brain–gene basis of psychophathological features of potential brain-based markers that have utility for assessing have begun to be incorporated into the template for the next ADHD and for predicting and evaluating treatment response. version of the DSM (DSM-V), which is expected to be released An integrative neuroscience framework encompasses: in 2013. While unrealistically optimistic expectations regarding • Consolidation of integrative theoretical models that provide a single brain–gene dysfunction linkages still remain, the essen- basis for understanding the range of thinking, emotion, feeling tial plan for converging biology with ‘signs and symptoms’ into and self-regulation disturbances in ADHD, as well as the links DSM-V points a way forward for integration: “It is our goal
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