Is there an inverse relationship between Down's syndrome and bipolar affective disorder? Literature review and genetic implications.

Several authors have suggested the existence of an inverse relationship between bipolar affective disorder and Down's syndrome (DS). The present authors have examined this hypothesis by a critical review of the literature. The present findings are consistent with a reduced rate of bipolar disorder in subjects with DS when compared with non-DS mentally retarded adults and with the general population. Thus, possession of an extra copy of chromosome 21 may confer protection against bipolar disorder. This could be the result of non-specific mechanisms or the action of a disease-modifying gene. However, the most interesting possibility is that either dominant or recessive alleles act at a major susceptibility locus for bipolar disorder on chromosome 21. Testable predictions result from the major susceptibility locus models. In order to investigate these hypotheses further, the present authors suggest the following: (1) further studies of the prevalence of bipolar disorder in DS; and (2) the reporting of all cases of bipolar disorder in trisomy 21 with details of the meiotic origin of the non-disjunction and details about affective disorder in relatives of the proband.