LINKAGE ANALYSIS OF CANDIDATE LOCI IN FAMILIES WITH RECURRENT MAJOR DEPRESSION

Recurrent major depression, RMD, is characterized by the occurrence of depressive episodes in the absence of mania and/or hypomania. In link age studies, RMD (or, in general, unipolar depression) are frequently grouped together with bipolar illnesses into a broad definition of aff ective disorders. However, twin studies suggest that RMD and bipolar d isorders might have different genetic determinants. The objective of t his study was to test a set of families with RMD for linkage to chromo somes that have been recently proposed to contain susceptibility loci for bipolar disorders: chromosomes 16, 18, 21 and the short arm of chr omosome 4. We analysed five large families from the northern part of S weden ascertained through a proband with RMD and containing several pa tients with RMD. For the genetic analysis, we included only severely a ffected individuals (those who had at least three episodes that requir ed medical treatment) to increase the chances of finding a larger degr ee of genetic determination. The genetic model led to a total disease prevalence of 5% in females and 3% in males. We did not find significa nt evidence for linkage to any of the candidate chromosomes in the com bined family set. Only one of the families showed a slight indication for linkage with markers from the pericentromeric region of chromosome 18. A genome scan analysis on an extended collaborative family materi al with severely affected individuals with RMD should be performed to evaluate whether RMD and bipolar disorders have a different genetic et iology.