BEHAVIORAL NEUROPHARMACOLOGY

Having an appreciation for neurobiologic complexity in developmentally disabled children and adolescents with behavior disorders improves ou r ability to treat them with drugs that have become increasingly speci fic in their effects. Reductionist analysis of phenotypic and genotypi c disorders improves our understanding of the pathogenesis of unique p atterns of adverse behaviors. Although drugs can be effective for trea ting specific behaviors, the cerebral mechanisms underlying these beha viors are not simple or linear in their pathways from genotype to phen otype. Our emerging knowledge about Lesch-Nyhan disease demonstrates u nexpected complexity from a single abnormal gene of purine metabolism and its diverse effects on cells, receptors, and neurotransmitters tha t produce characteristic self-injurious behaviors. Several hypotheses for pathogenesis suggest ways that a defective gene might affect the d eveloping brain and strategies for treatment. For disorders that have several abnormal genes, such as autism and bipolar disorder, biologic effects are likely to be even more complex due to gene interactions an d compounded with added environmental effects, learning, and experienc e. There is a high incidence of comorbidity in conditions that affect behavior in children with mental retardation and developmental disabil ities. Accurate diagnoses and follow-up are essential for advanced neu ropharmacology to be effective. Guidelines for the evaluation and trea tment of patients who have comorbid neuropsychiatric disorders are sug gested. (C) 1998 Wiley-Liss, Inc.