Molecular Genetics of Attention-Deficit/Hyperactivity Disorder

The Prevalence of DSM-IV Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review

Attention-Deficit/Hyperactivity Disorder: A Selective Overview

This review discusses conceptual issues in relating temperament to psychopathology, including the disputed relation of temperament to personality in children. A potential integrative framework is discussed that links trait and biological markers of temperament (reactive, incentive-response tendencies) with regulatory processes. This framework is utilized to highlight potential temperamental pathways to specific forms of psychopathology, noting that in some instances their relations may reflect a spectrum model (with psychopathology closely related as an extreme of a temperament-based trait), but in many instances it likely reflects a vulnerability-transaction set of processes. Conduct disorder involves at least two temperamental paths, one emanating from low fear response and one from either high incentive approach or high anger reactivity. Attention deficit hyperactivity disorder also involves at least two temperament pathways, one involving extremely low effortful control and the other likely involving strong approach. Anxiety disorders appear to result from the confluence of high negative emotionality and low effortful control. Hypotheses for future research are presented and limitations discussed.

Temperament and developmental psychopathology

Psychological heterogeneity in AD/HD—a dual pathway model of behaviour and cognition

Objective To investigate heritability and continuum versus categorical approaches to attention-deficit hyperactivity disorder (ADHD), using a large-scale twin sample. Method A cohort of 1,938 families with twins and siblings aged 4 to 12 years, recruited from the Australian National Health and Medical Research Council Twin Registry, was assessed for ADHD using a DSM-III-R-based maternal rating scale. Probandwise concordance rates and correlations in monozygotic and dizygotic twins and siblings were calculated, and heritability was examined using the De Fries and Fulker regression technique. Results There was a narrow (additive) heritability of 0.75 to 0.91 which was robust across familial relationships (twin, sibling, and twin-sibling) and across definitions of ADHD as part of a continuum or as a disorder with various symptom cutoffs. There was no evidence for nonadditive genetic variation or for shared family environmental effects. Conclusions These findings suggest that ADHD is best viewed as the extreme of a behavior that varies genetically throughout the entire population rather than as a disorder with discrete determinants. This has implications for the classification of ADHD and for the identification of genes for this behavior, as well as implications for diagnosis and treatment.

Attention-Deficit Hyperactivity Disorder: A Category or a Continuum? Genetic Analysis of a Large-Scale Twin Study

Objective To examine gender differences in attention-deficit/hyperactivity disorder (“ADHD”) symptom comorbidity with “oppositional defiant disorder”, “conduct disorder”, “separation anxiety disorder”, “generalized anxiety disorder”, speech therapy, and remedial reading in children. Method From 1994 to 1995, data from a large sample (N = 4,371) of twins and siblings studied in the Australian Twin ADHD Project were obtained by mailed DSM-IV-based questionnaires, investigating patterns of comorbidity in the three subtypes of “ADHD”: “inattentive”, “hyperactive/impulsive”, and “combined”. A total of 1,550 questionnaires were returned (87%) over the next 12 to 18 months. Results Analysis of variance showed significant between-group differences in males and females for inattention and hyperactive/impulsive symptom counts with higher rates of “oppositional defiant disorder” and “conduct disorder” in males, and higher rates of “separation anxiety disorder” in females indicating internalizing disorders are more common in females and externalizing disorders are occurring more often in males. Differences were found between the “ADHD” subtypes and the no ADHD category for all comorbid conditions, for both males and females. Children without ADHD consistently had fewer symptoms, while children with the combined subtype showed consistently more comorbid symptoms indicating a strong relationship between high rates of externalizing symptoms and high rates of internalizing symptoms. Gender differences in speech therapy were significant only for the children without ADHD. The rates of “separation anxiety disorder” were higher in females with the “inattention” subtype and the rate of “generalized anxiety disorder” higher for females with the “combined” subtype, indicating that the subtypes of ADHD were associated with these internalizing disorders in different ways. Conclusions Although comorbidity differs among ADHD subtypes, there were no significant gender differences in comorbidity for externalizing disorders. Inattentive girls may present with anxiety. Clinical approaches for both males and females should be sensitive to possible language and reading problems.

Gender differences in ADHD subtype comorbidity.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioural difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.

Recruitment and attrition in twin register studies of childhood behavior: the example of the Australian Twin ADHD Project.

Although attention deficit – hyperactivity disorder (ADHD) has a distinct developmental progression and a substantial genetic component, very little is known about the genetic contribution to its development and the question of whether the same genes contribute to ADHD throughout childhood and into adolescence. Data from one of the most extensive twin databases, the Australian Twin ADHD Project (ATAP) have shown that ADHD is inherited as a behavioural dimension rather than as a discrete disorder. Behavioural genetic analysis is used in this study with both cross-sectional and longitudinal analyses of inattention and hyperactivity – impulsivity symptoms of ADHD to demonstrate that much of the consistency in behaviour during childhood and early adolescence is due to genetic influences. Genetic analyses help identify environmental influences that impact upon symptoms of inattention and hyperactivity – impulsivity. It is emphasised that the main function of genetic analysis does not lie in simply estimating t...

Michael McStephen

Papers

Attention-Deficit Hyperactivity Disorder: A Category or a Continuum? Genetic Analysis of a Large-Scale Twin Study

Gender differences in ADHD subtype comorbidity.

Recruitment and attrition in twin register studies of childhood behavior: the example of the Australian Twin ADHD Project.

Attention deficit - hyperactivity disorder in twins: A developmental genetic analysis

Common Family Environment and The Comorbidity Among the Disruptive Behavior Disorders