ARTICLES
Familial Clustering of Symptoms and Disruptive Behaviors in Multiplex Families With Attention-Deficit/Hyperactivity Disorder

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ABSTRACT

Objective

To examine familial clustering of attention-deficit/hyperactivity disorder (ADHD), ADHD subtypes, symptoms, and oppositional behaviors in affected sibling pairs (ASPs) and their parents.

Method

One hundred thirty-two ASPs, ranging in age from 5 to 25 years and ascertained through clinic and volunteer referrals, were examined for DSM-IV ADHD subtypes, oppositional defiant disorder (ODD), and conduct disorder (CD) with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Two hundred fifty-six parents in these families were assessed by means of the SADS-Lifetime version, Modified for the Study of Anxiety Disorders, Updated for DSM-IV (SADS-LA-IV), and the Behavioral Disorders supplement of the K-SADS-PL to determine ADHD, ODD, and CD.

Results

Fifty-five percent of families ascertained through an ASP have at least one parent with a lifetime diagnosis of ADHD. The frequency of ADHD in at least one parent was higher in families with at least one affected girl (63%) than in families with only affected boys (45%) (p = .02). There was no evidence that affected siblings or parents within ASP families showed similar patterns of ADHD symptoms, such as ADHD subtype classification. In contrast, CD significantly clustered in ASP families.

Conclusions

The sex difference in prevalence of ADHD among ASPs is consistent with a model of inheritance in which girls require a greater loading of familial influences to develop ADHD. The lack of familial clustering of ADHD symptoms within ASP families suggests that hyperactive and inattentive symptoms reflect common familial underpinnings and not unique familial effects. In contrast, CD seems to reflect unique familial underpinnings distinct from those underlying ADHD.

Section snippets

Sample

One hundred thirty-two ASP families including 283 affected members and 256 parents (131 mothers, 125 fathers) completed phenotype investigations. Seven parents refused to participate in the psychiatric evaluations and one parent was deceased. Families were ascertained through at least 1 ASP from the following sources: clinical referrals (n = 44), schools (n = 8), and responses to advertisements (n = 80) in newsletters (e.g., CHADD), community newspapers, or flyers distributed at parent meetings

RESULTS

For all analyses except tests of familial clustering by sex of the ASPs, the eldest two affected siblings were used per family to ensure independence of the sibling pairs. The diagnostic characteristics and demographics of the eldest and second eldest ASP members are shown in Table 2.

Approximately 70% were boys, and the mean IQ was above average, with the siblings differing in age by about 3 years. Eight families (6%) had an ASP member with a Full Scale IQ score between 70 and 80. The majority

DISCUSSION

Understanding the genetic etiology of ADHD could significantly improve our diagnosis, early detection, and the development of better interventions in the treatment of this condition. In the current study, we use ASP families to elucidate phenotypic variability that may reflect underlying genetic heterogeneity. By containing at least 1 ASP, this sample can be considered “familial” and may represent a more homogeneous sample than one ascertained through a single ADHD proband. The rate of ADHD in

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    This work was supported by NIMH grant MH58277 to Dr. Smalley. The authors thank Erica Carr, Erin Cantwell, Amy Lightbody, Rita Cantor, and Art Woodward for assistance on this project, and all the families that contributed their time to this research. This project was inspired by Dennis Cantwell's lifelong commitment to understanding and treating ADHD.

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