Attention-Deficit Hyperactivity Disorder

Abstract

At the end of the twentieth century, there were great expectations that neuroscience discoveries catalyzed by the Decade of the Brain would result in enhanced clinical practices for treatment and prevention of Attention-Deficit/Hyperactivity Disorder (ADHD) or Hyperkinetic Disorder (HKD), which were summarized by an international collaborative group of child psychologists and psychiatrists (Swanson JM, Sergeant J, Taylor E, Sonuga-Barke EJS, Jensen PS, Cantwell DP: Lancet 351:429–433, 1998). Based on five topics (diagnosis, epidemiology, treatment, prognosis, and pathophysiology), we suggested that “brain imaging studies implicate the frontal basal-ganglia neural networks,” “molecular genetic studies implicate the dopamine pathways that modulate and integrate neural activity of these networks,” and “neuroanatomical and biochemical abnormalities provide firm ground to build an understanding of the biological bases of ADHD/HKD.” Almost 20 years later, the collaborative group was reconvened (Swanson JM, Sergeant JA, Taylor EA, Sonuga-Barke EJS, Jensen PS, Castellanos FX: Chapter 142: attention deficit hyperactivity disorder. In: Pfaff DW, Volkow ND (eds) Neuroscience in the 21st century. Springer, New York, 2016) and prepared a chapter for the second edition of Neuroscience in the twenty-first Century. During the beginning of the twenty-first century, we noted progress was made, but problems emerged that muted the previous hopes and expectations. We concluded “the underlying pathophysiology of ADHD is much more complex than suggested by research from the twentieth century,” “ADHD is not a unitary condition and instead is a final common pathway of many underlying biologic and environmental factors,” and “research should clarify these factors and enable the refinement of available intervention and the development of new interventions for ADHD across the life span.” For this revision, we reconstituted the group to provide another update based on the same five topics that were addressed previously. Brief reviews are provided to summarize the (a) revisions to the official diagnostic criteria that define essential features of the modern disorder, (b) estimates of the administrative prevalence in different countries of the recognized disorder, (c) trends in use of stimulant and non-stimulant medications for treatment of the symptomatic disorder, (d) expectations of the course of the neurodevelopmental disorder, and (e) speculations about the biological and environmental causes of the complex disorder.

Appendix A

^aWhat is the current controversy about categorical diagnosis? Even though the categorical approach was retained in DSM-5 and ICD-11 and the criteria and label for ADHD converged (see First et al. 2021), the controversy about the dimensional approach has continued. For example, Thapar and Cooper (2016) suggested “for clinical practice, there is need for strict categories, otherwise diagnostic spread would become at best unhelpful and at worst risky and unethical [and] application of evidence-based treatments would become impossible.” The proposed categories may serve as a vehicle for the development of evidence-based clinical practices, despite strong evidence from research that ADHD is dimensional. The general approach applied to revise diagnostic categories in ICD-11 (including the transition from the HKD to the ADHD diagnosis) has been described as “incorporation of dimensional approaches within the context of an explicitly categorical system” (see Reed et al. 2019), but the categorical-dimensional debate (including consideration of the RDoC approach) has not been resolved (see Clark et al. 2017).

^bAre fundamental statistical assumptions met regarding severity and impairment? Two recent collaborative studies (including some authors of this chapter) addressed interesting statistical properties of measures of severity and impairment of ADHD relevant to this controversy and highlight fundamental issues. Alexander et al. (2020) applied the item-rating approach of the Strengths and Weaknesses of ADHD and Normal behavior (SWAN) rating scale to most psychiatric disorders of childhood and created the Extended-SWAN. This avoids categorical truncation of ratings of possible strengths (at the item level) and allows ratings across the full range of underlying behavior, which provides population norms that have near-normal distributions instead of highly skewed distributions. Arildskov et al. (2021) questioned the traditional categorical definition of impairment (based on the assumption of a qualitative threshold for symptom severity where impairment would suddenly increase). This study described a linear relationship between severity of impairment and severity of ADHD symptoms, providing no evidence for a discrete, nonarbitrary symptom severity threshold that is associated with a marked step increase in impairment. This led to a conclusion that specification of a symptom-count cutoff (as in DSM-5) creates a challenge (“clinicians need to make a categorical decision while no such categorical threshold seems to exist”).

^cWhat is the new superordinate classification of “Neurodevelopmental Disorder?” In both DSM-5 and ICD-11, ADHD is classified as a neurodevelopmental disorder (NDD), which replaced the previous superordinate classification as a “disruptive behavior disorder” (in DSM-IV) and “behavioral and emotional disorders with onset in childhood or adolescence” (in ICD-10). According to Falissard (2021), the term NDD has origins from the field of neurology (see where it was used to describe disorders such as epilepsy, cerebral palsy and mental retardation, with poor prognosis and limited association with psychosocial factors), and the current concept of NDD in psychiatry became widely accepted for use in child psychiatry after Bishop and Rutter et al. (2008) proposed a conceptual definition in a textbook based on specific characteristics (early onset, delayed CNS maturation, and steady course). The NDD concept may become problematic in the future for the superordinate classification of ADHD in DSM-5 and ICD-11, since the early onset requirement for ADHD was relaxed and some even suggest should be eliminated (see Asherson et al. 2019), the NDD category was broadened and some suggest this may undermine clinical utility regarding treatment and prognosis (see Szatmari in Stein et al. 2020), and “presentations” of ADHD can change and symptoms may dissipate or wax and wane over time (see Moffitt et al. 2015; Sibley et al. 2021). These issues may question the validity of superordinate classification of ADHD as a neurodevelopmental rather than behavioral disorder (see Norbury and Sparks 2013).

^dIs “Emotional Dysregulation” central to ADHD? Some investigators suggest ADHD should be conceptualized as a disorder of self-regulation, which encompasses not only deficits in regulation of attention, activity, and impulses but also emotions. Emotional dysregulation may not be properly reflected in current diagnostic criteria. It has been characterized by many investigators as (a) “high negative and positive emotionality [and] deficient control processes” (Martel 2009), (b) “irritability and mood lability” (Shaw et al. 2014), (c) “a deficiency [in] self-regulation of frustration, impatience, and anger” (Barkley 2015), (d) “difficulties with managing anger, frustration, and other negative emotions [and] positive emotions” (Bunford et al. 2015), (e) “reactive to stressful and/or frustrating situations” (Graziano and Garcia 2016), (f) “emotionally immature, overly exuberant, rambunctious, low tolerance for anger and frustration” (Bunford et al. 2015), and (e) “approach-related dysregulation and surgency-sensation seeking” that extends beyond irritability (Nigg et al., 2020a). These characterizations support a broad conceptualization of ADHD as a disorder of self-regulation, involving not only regulation of cognitive processes but also of emotions (Faraone et al. 2019; Nigg et al. 2020a, b. However, emotional dysregulation may occur in many mental disorders and thus be considered a transdiagnostic correlate, and specific aspects implicated in ADHD need to be isolated (Aldao et al. 2016). This is not a recent addition. In our previous 1998 seminar (part of the centennial celebration of the Lancet and some classic articles published during the twentieth century), we referred to Still (1902), who in eloquent case reports included a description of some children with “morbid exaggeration of emotional excitability.”

^eWhat is slow or sluggish cognitive tempo (SCT)? Some investigators suggest children with the inattentive presentation of ADHD show additional behaviors that are not captured by the diagnostic criteria for inattentiveness in DSM-5 or ICD-11, such as daydreaming, staring, mental fogginess, confusion, hypoactivity, sluggishness, slow movement, lethargy, apathy, and sleepiness (Becker et al. 2016; Becker 2020). Since the 1980s, this constellation of associated features has been described as slow or sluggish cognitive tempo (SCT), which can be reliably assessed across informants and uniquely predicts higher depressive symptoms, academic impairment, and social impairment. This may inform treatment choice and prognosis, since cases with SCT may have reduced benefit associated with treatment with stimulant medication (Becker 2020) and increased benefit associated with allowances for extra time to complete work or take tests (Kofler et al. 2019), due to a combination of weak or slow working memory capacity (requiring extra time to rearrange active contents) and average to strong inhibition systems (that terminate further input and prevent intended behaviors). This is not a recent addition, either, since it was suggested previously in the classic historical accounts of childhood mental disorders in the early twentieth century (Still 1902) and even earlier by Hoffman (1848) in a popular nineteenth century children’s book of “funny stories and whimsical pictures” that described prototype children with abnormal behaviors remarkably like symptoms of modern psychiatric disorders of childhood (e.g., “Johnny Look-in-the-Air,” with symptoms of SCT).