title: Attention deficit hyperactivity disorder in obese melanocortin-4-receptor (MC4R) deficient subjects: a newly described expression of MC4R deficiency.
abstract: Attention deficit hyperactivity disorder (ADHD) is a heterogeneous highly heritable disorder which has recently been described to be comorbid in obese subjects. This study investigated phenotype/genotype associations in a consanguineous family with genetic obesity due to the melanocortin-4-receptor (MC4R) (C271R) mutation. MC4R deficiency disrupts hunger/satiety regulation resulting in abnormal eating behaviors. To date, the behavioral/psychiatric characteristics of MC4R deficiency have not been described except for a possible association with Binge Eating Disorder. Twenty-nine subjects of a family known to carry the MC4R (C271R) mutation, were genotyped for the mutation and underwent extensive evaluations in search for physical/psychiatric phenotype characteristics. Subjects originated from proband nuclear families with morbid obese children (BMI percentile > 97%). All probands were homozygous for the MC4R (C271R) mutation. ADHD prevalence was higher than expected only in the groups carrying the homozygous or heterozygous mutation (P = 0.00057, 0.0028, respectively). An obvious difference was observed between the homozygous group and the rest of the family in terms of obesity: homozygous subjects had childhood morbid obesity whereas heterozygous subjects included lean, normal weight and later onset obese subjects. A significant difference was found in ADHD prevalence between the homozygous MC4R (C271R) group (80%) and the rest of the family (22%) (P = 0.033) and a significant trend was found between ADHD prevalence and the number of MC4R (C271R) alleles (P = 0.0267). We conclude that in our sample, the MC4R (C271R) mutation causing obesity, is in association with ADHD. Identifying specific subgroups in which the comorbidity of obesity and ADHD occur may contribute to the understanding of the underlying molecular mechanisms.
authors.affiliation: Department of Child and Adolescent Psychiatry, Hadassah Hebrew University Medical Center, Jerusalem, Israel. anatagranat@013.net
authors.forename: Anat
authors.initials: A
authors.lastname: Agranat-Meged
authors.forename: Yoad
authors.initials: Y
authors.lastname: Ghanadri
authors.forename: Iris
authors.initials: I
authors.lastname: Eisenberg
authors.forename: Ziva
authors.initials: Z
authors.lastname: Ben Neriah
authors.forename: Eva
authors.initials: E
authors.lastname: Kieselstein-Gross
authors.forename: Stella
authors.initials: S
authors.lastname: Mitrani-Rosenbaum
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D009679:Nuclear Family; D009765:Obesity / Q000235:genetics*; D010290:Parents; D010375:Pedigree; D015995:Prevalence; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency* / Q000235:genetics; D035781:Siblings
chemical_list: D044105:Receptor, Melanocortin, Type 4