Attention, Genes and ADHD

Florence Levy, David Hay

• Publisher: Psychology Press
• Year: 2021
• ISBN:
  9781317710059
• Edition: 1
• Topic: Medicine
• Subtopic: Genetics in Medicine

This book focuses on the application of behaviour genetic approaches to twin studies, and reviews diagnostic to Attention Deficit Hyperactivity Disorder (ADHD), the relationships between reading, spelling and ADHD, and family and genetic influences on speech and speech and language.

1	Introduction Florence Levy

Clinical interest in problems of overactivity and attention goes back to lectures to the Royal Academy of Physicians by George Still (1902), who described a group of children manifesting a deficit in “volitional inhibition” or a deficit of moral control! According to Barkley (1997), Still’s observations were astute in describing many of the associated features of ADHD, now corroborated in research more than 50–90 years later. These features include an over representation of males, an aggregation of alcoholism, criminal conduct and depression among biological relatives, a familial predisposition to the disorder, and the possibility of the disorder arising from acquired injury to the nervous system.

Since that time, there have been many theories about the nature of similar syndromes. A syndrome of overactivity and distractibility was described following the pandemic of encephalitis lethargica that swept Europe in 1917–1918, giving rise to theories of Minimal Brain Dysfunction (MBD) (Kessler, 1980). In the 1950s and 1960s hyperactivity and poor impulse control were thought to be due to poor thalamic filtering of stimuli entering the brain (Laufer, Denhoff, & Solomons, 1957).

Another milestone in the history of ADHD was the observation of Charles Bradley (1937) that benzedrine, a central nervous system stimulant, had a calming affect on the behaviour of overactive children. This finding led to the use of dexamphetamine and methylphenidate as a treatment for hyperactivity, and the use of these medications has been particularly developed in North America (Wilens & Biederman, 1992; Greenhill, 1992). A multisite study (Arnold et al., 1997; MTA Cooperative Group, 1999) has compared the use of stimulant medication alone, with stimulant medication combined with multimodal treatments. A recent text by Solanto, Arnsten and Castellanos (2001) provides an excellent review of the basic and clinical neuroscience of stimulant drugs and ADHD.

There has been a continuing divergence between North American clinicians, who view Attention Deficit Hyperactivity Disorder (ADHD) as a developmental disorder with substantial biological origins, and UK clinicians, who place greater emphasis on conduct problems originating from poor parental management. The shift to an emphasis on inattention in North American studies began with the work of Virginia Douglas (1972), who hypothesised that a deficit in the capacity to sustain attention underlay observed symptoms of hyperactivity and impulse control. The work of Douglas (1972, 1983) influenced the re-categorisation of the disorder in the third edition of the Diagnostic and Statistical Manual (DSM-III; American Psychiatric Association [APA], 1980) as Attention Deficit Disorder (ADD) with and without Hyperactivity. The DSM-III conceptualised ADD with Hyperactivity as a tri-dimensional disorder characterised by developmentally inappropriate inattention, impulsivity and hyperactivity with symptoms and cut-offs described to operationalise the diagnosis. The revised edition (DSM-III-R, APA, 1987) on the other hand, listed 14 symptoms, some related to attention and some to impulsivity and hyperactivity in descending order of discrimination (according to field trials), requiring 8 symptoms for a diagnosis. The fourth edition of the Diagnostic and Statistical Manual (DSM-IV, APA, 1994) includes separate diagnostic criteria for symptoms of inattention and hyperactivity/impulsivity. Thus, ADHD is now diagnosable as three subtypes: Predominantly Inattentive, Predominantly Hyperactive/Impulsive, and a Combined type.

Swanson (1997) has pointed out that while the DSM-IV and International Classification of Disease—10th revision (ICD-10; World Health Organisation [WHO], 1992) use similar classification schemes for ADHD and Hyperkinetic Disorder (HD), the ICD also describes a combined Hyper-kinetic Conduct Disorder category. This has important implications for the diagnosis of comorbid disruptive behaviour disorders. A substantial proportion of children with a diagnosis of ADHD and referred to clinics have comorbid Oppositional Defiant Disorder and/or Conduct Disorder on DSM-IV diagnosis, yet in Europe might rather obtain a diagnosis of Hyperkinetic Conduct Disorder. This makes a diagnosis of HD less likely in European countries, when children have comorbid symptoms, than in the US, despite virtually identical symptoms. Thus, the issue of the relationship with ADHD of comorbid symptomatology remains an important theoretical and classification issue, which may be clarified by behaviour genetic studies.

In his 1997 monograph, Barkley made a number of critiques of the DSM-IV approach. He pointed out that it was not clear that ADHD-I, the predominantly inattentive type of ADHD, was actually a subtype of ADHD sharing a common attention deficit with other types. The Inattentive subtype manifests greater stability over time and is more predictive of school performance problems and possibly reading difficulties. He questioned whether young ADHD—predominantly Hyperactive/Impulsive (ADHD-HI)—children, who do not require Inattention symptoms for diagnosis, eventually move into the ADHD-Combined type (ADHD-C) over time, and why hyperactive-impulsive symptoms decline sharply over time. He also asked how applicable were the diagnostic thresholds set for the two main DSM-IV subtypes to age groups outside those used in the DSM-IV field trial (ages 4–16 years). An adult outcome study by Barkley, Fisher, Fletcher, and Smallish (1997) showed that when self-report of DSM criteria was used, persistence into adulthood was 3%, but when an empirical (age referenced) definition was used, persistence was increased to 28%.

Barkley (1997) suggested that ADHD may need to be defined as a developmentally relative disorder at the extreme end of a normal psychological trait. This trait probably undergoes developmental elaboration and maturation with age, as do language ability, memory, and intelligence. He suggested that current criteria are descriptive and atheoretical, and do not make predictions about associated features or life course.

A paper by Hill and Schoener (1996) has sparked controversy about whether or not there is an age-dependent decline of attention deficit hyper-activity disorder in adolescence and adulthood. The authors analysed data from nine prospective ADHD studies in which original diagnosis was made in childhood, and follow-up evaluations were made into late adolescence. They fitted an exponential function which predicted a decline in symptoms with age such that, assuming a mean prevalence of 4% at age 9, this would drop to 0.84% at age 20; to 0.21% at age 30; to 0.05% at age 40; and to 0.01% at age 50.

Barkley (1997) has queried the Hill and Schoener conclusions, on the grounds of unreliability of measurement of the disorder across time, and insensitivity of DSM criteria with increasing age. The controversy raises issues about whether or not fundamental changes in the expression of ADHD occur with development, or whether compensatory mechanisms minimise expression of the disorder. Therefore, important developmental issues in relation to ADHD still require resolution.

Sergeant (1995) has discussed the difference between quantitative and categorical approaches to the diagnosis of ADHD. He pointed out that while categorical approaches may be useful, their validity should be tested by prospective checks on stability and family studies. He also pointed out that in instances where classification studies introduce major shifts (as has happened with the DSM), it may be useful to use a broad array of quantitative symptom scores, as are employed by the Child Behaviour Checklist (CBCL; Achenbach, 1991). The CBCL provides quantitative scores on scales reflecting different domains of psychopathology, allowing an examination of comorbidity issues.

Taylor, Sandberg, Thorley, and Giles (1991) have pointed out that the predictive significance of attention deficit vs hyperactive symptoms varies in different studies (Fergusson & Horwood, 1993; Gittelman, Mannuzza,

Shenker, & Bonagura, 1985; McGee, Williams, & Silva, 1987). British and

North American studies have emphasised Conduct Disorder/Attention Deficit Disorder as outcomes of hyperactivity. Taylor et al. (1991) pointed out that prospective longitudinal studies of epidemiologically defined groups, and of a clinical series, are needed to answer questions of predictive significance, including clinical case controls and subthreshold levels of hyperactivity. Such studies would examine the predictive implications of heterogeneity and comorbidity with associated behaviour disorders. Comorbid aggression, conduct disorder, learning disability or anxiety may represent subtypes of ADHD.

Taylor (1998) has also discussed confusion arising from the terminology “attention deficit disorder”, particularly since the advent of DSM-IV subtypes, inattentiveness and overactivity/impulsivity. He pointed out that it is possible to have ADHD without being inattentive. On the other hand, ICD-10 requires inattentiveness for a diagnosis of hyperkinetic disorder. The hypothesis of a unitary attention deficit may be misleading because of the complexities of determining the transition from brain dysfunction, through cognitive dysfunction, into behavioural presentation.

The development of operational criteria is complex. Taylor (1998) pointed out that the distinction between oppositional behaviour and inattentiveness is a frequent challenge to the clinician, because a very oppositional child may not engage in tasks long enough to allow satisfactory judgements about task orientation. In other words, motivation may interact with attention. Many definitions used in rating scales and diagnostic schemes refer to inferences and value judgements, rather than to observable behaviour. For example, distractibility, short attention span, and sensation seeking might all be terms used to describe similar behaviour.

Hudziak and Todd (1993) have discussed possible phenotypic subtyping of ADHD, including subtyping by comorbidity, family studies, relationship to mood disorders, learning disability, gender, parental ADHD, laboratory methods, or biological markers. They concluded that available data supported subtyping by comorbidity, but familial relationships did not support co-segregation in families. While these critiques in relation to developmental, classification, and comorbidity issues are challenging and heuristic, they indicate a fundamental problem in assigning diagnostic criteria on the basis of factor-analytic studies of parent and teacher ratings. Many of the questions posed may not be answerable by phenotypic investigations. According to Taylor (1998) the development of molecular genetics means that different genetic influences will be measured rather than inferred, while developments in experimental psychology should allow for clearer descriptions of what is impaired by different genes.

Rutter, Silberg, O’Connor, and Simonoff (1999) have reviewed advances in quantitative and molecular genetics, in relation to shifts in research strategies, multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies), and new molecular techniques.

The present authors believe that behavioural and molecular genetic approaches enable examination of genetic and environmental influences on latent behavioural traits, as well as genetic and environmental influences on comorbidity and outcome, more adequately than can phenotypic approaches alone.

REFERENCES

Achenbach, T.M. (1991). Manual for the Child Behaviour Checklist 4–18 and 1991 Profile. Burlington, VT: University of Vermont, Department of Psychiatry.

American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders (3rd ed.) [DSM-III]. Washington, DC: Author.

American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed., rev.) [DSM-III-R]. Washington, DC: Author.

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.) [DSM-IV]. Washington, DC: Author.

Arnold, L.E., Abikoff, H.B., Cantwell, D.P., Conners, C.K., Elliott, G., Hechtman, L., Hinshaw, S.P., Hoza, B., Jensen, P.S., Kraemer, H.C., March, J.S., Newcorn, J.H., Pelham, W.E., Richters, J.E., Schiller, E., Severe, J.B., Swanson, J.M., Vereen, D., & Wells, K.C. (1997). National Institute of Mental Health collaborative multi-modal treatment study of children with ADHD (the MTA): Design challenges and choices. Archives of General Psychiatry, 54, 865–870.

Barkley, R.A. (1997). ADHD and the nature of self-control. New York/London: Guildford Press.

Barkley, R.A., Fischer, M., Fletcher, K., & Smallish, L. (1997). Adult outcome of hyperactive children: I. Psychiatric status and psychological adjustment. Unpublished manuscript.

Bradley, C. (1937). The behaviour of children receiving benzedrine. American Journal of Psychiatry, 94, 557–585.

Douglas, V.I. (1972). Stop, look and li...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• List of contributors
• Preface
• Acknowledgements
• 1 Introduction
• 2 Introduction to the genetic analysis of attentional disorders
• 3 The diagnostic genetics of ADHD symptoms and subtypes
• 4 The developmental genetics of ADHD
• 5 Familial and genetic bases of speech and language disorders
• 6 Comorbidity of reading/spelling disability and ADHD
• 7 Causes of the overlap among symptoms of ADHD, Oppositional Defiant Disorder, and Conduct Disorder
• 8 Aetiology of the sex difference in the prevalence of DSM-III-R ADHD: a comparison of two models
• 9 Single gene studies of ADHD
• 10 Molecular genetics of ADHD
• 11 The genetic relationship between ADHD and Gilles de la Tourette syndrome
• 12 Implications of genetic studies of attention problems for education and intervention
• 13 Child psychiatry in the era following sequencing the genome
• Author index
• Subject index