LINKAGE AND ASSOCIATION ANALYSIS OF CHROMOSOMAL REGIONS CONTAINING GENES RELATED TO NEUROENDOCRINE OR SEROTONIN FUNCTION IN FAMILIES WITH EARLY-ONSET, RECURRENT MAJOR DEPRESSION

Recurrent unipolar depression with an early age of onset is a severe f orm of unipolar depression that has both genetic and environmental com ponents, We genotyped the members of 16 families identified by proband s with early onset (less than or equal to 25 years) recurrent unipolar , major depression for 38 simple sequence tandem repeat polymorphisms (SSTRPs) from chromosomal regions containing 12 genes involved in neur oendocrine or serotonergic functioning, Pairwise linkage analysis was performed with the software package FASTLINK. The affected phenotype w as defined four ways, and both dominant and recessive models of depres sion were analyzed. Seven SSTRPs showed lod scores >1.00 at theta valu es between 0.10-0.20. The members of an additional 18 families were ge notyped for these seven SSTRPs, and the complete sample of 34 families was evaluated using lod score analysis, affected pedigree member link age analysis, and within-family association analysis. Evidence for lin kage between D11S929 and affective illness remained positive, necessit ating the analysis of four additional SSTRPs within 3 cM of D11S929, A fter all confirmatory analyses were completed, no evidence suggestive of linkage remained between any of the 38 SSTRPs and the affected phen otypes. (C) 1998 Wiley-Liss, Inc.