Genetic Components of Depression Identified

October 1, 2003
Volume 20, Issue 10

Zubenko and colleagues recently released results from the first genome-wide linkage survey for genetic loci that influence the development of unipolar mood disorders in 81 families identified by individuals with recurrent, early-onset, major depressive disorder. The survey found 19 loci that appear to influence vulnerability to depressive disorders.

The 5-HTT gene was found to predict an individual's sensitivity to stressful events (Science 2003;301[5631]:386-389). Researchers divided 847 members of the Dunedin Multidisciplinary Health and Development Study into three groups based on their 5-HTT gene-linked polymorphic region genotype: those with two copies of the short allele (s/s homozygotes; 17%), one copy of the short allele (s/l heterozygotes; 51%), and two copies of the long allele (l/l homozygotes; 31%). Stressful life events that occurred after the 21st birthday and before the 26th were assessed.

Self-reports of depressive symptoms due to life events at age 26 were stronger in subjects with one short allele than l/l homozygotes. Subjects with a short allele whose life events occurred after their 21st birthday experienced an increase in depressive symptoms between the ages of 21 to 26. Stressful life events predicted a diagnosis of major depression in subjects with a short allele but not in l/l homozygotes. In addition, the researchers found that 33% of individuals with one short allele suffering four or more stressful life events developed depression, compared to 17% of the l/l homozygotes--RG