Attention-Deficit/Hyperactivity Disorder and Comorbid Disruptive Behavior Disorders: Evidence of Pleiotropy and New Susceptibility Loci

• Published in: Biological psychiatry (1969) 2007-06, Vol.61 (12), p.1329-1339
• Main Authors: Jain, Mahim, Palacio, Luis Guillermo, Castellanos, F. Xavier, Palacio, Juan David, Pineda, David, Restrepo, Maria I, Muñoz, Juan F, Lopera, Francisco, Wallis, Deeann, Berg, Kate, Bailey-Wilson, Joan E, Arcos-Burgos, Mauricio, Muenke, Maximilian
• Format: Article
• Language: English
• Subjects: Addictive behaviors; ADHD; Adolescent; Adult and adolescent clinical studies; alcohol abuse/dependence; Alcoholism; Alcoholism and acute alcohol poisoning; Attention Deficit and Disruptive Behavior Disorders - epidemiology; Attention Deficit and Disruptive Behavior Disorders - genetics; Attention Deficit Disorder with Hyperactivity - epidemiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit disorders. Hyperactivity; Biological and medical sciences; Child; Child clinical studies; Child, Preschool; Chromosome Aberrations; Chromosome Mapping; Comorbidity; conduct disorder; Conduct Disorder - epidemiology; Conduct Disorder - genetics; Female; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium - genetics; Male; Medical sciences; nicotine dependence; oppositional defiant disorder; Phenotype; pleiotropy; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Factors; Social behavior disorders; Substance-Related Disorders - epidemiology; Substance-Related Disorders - genetics; Toxicology
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.06.026

Background Attention-deficit/hyperactivity disorder (ADHD) comorbid with oppositional defiant disorder (ODD) or conduct disorder (CD) and substance abuse/dependence seems to represent a specific subset within the phenotypic ADHD spectrum. Methods We applied complex segregation and linkage analyses in a set of multigenerational families densely segregating ADHD comorbid with ODD, CD, alcohol abuse/dependence, and nicotine dependence. Results Our data suggest that ADHD cosegregates with disruptive behaviors as a unique, phenotypically variable trait as evidenced by highly significant pair-wise linkages among: ADHD and ODD (logarithm of odds [LOD] = 14.19), ADHD and CD (LOD = 5.34), ODD and CD (LOD = 6.68), and CD and alcohol abuse/dependence (LOD = 3.98). In addition to previously reported ADHD susceptibility loci, we found evidence of linkage for comorbid ADHD phenotypes to loci at 8q24, 2p21-22.3, 5p13.1-p13.3, 12p11.23-13.3, 8q15, and 14q21.1-22.2. These results were replicated with an affected status phenotype derived from latent class clusters. Conclusions Patterns of cosegregation of ADHD with comorbidities can inform our understanding of the inheritance patterns not only of ADHD but also of disruptive behavioral disorders and alcohol abuse/dependence. Refining the comorbid ADHD phenotype by determining the cosegregation profile of specific comorbidities might be a powerful tool for defining significant regions of linkage.