Faint Genetic Signals

All this searching for the key to depression underneath the lamplight of serotonin is fine, but we need to remember that it takes a genome. When the book on the genetics of sadness is finally written, it will surely also include entries on the enzymes that synthesize the chemical and on the receptors that take up the signal. It is increasingly apparent, though, that it must include dozens if not hundreds of other chapters that can barely be sketched in outline yet.

The search continues using more traditional approaches. Linkage mapping in pairs of affected twins has turned up a dozen possibilities. This is where researchers look for parts of the genome shared by non-identical twins who both have the disease. As a matter of logic, siblings always share about a half of their genes, but if the same region of a chromosome is shared in a sizeable fraction of hundreds of twins, it suggests that there is a gene thereabouts. One strong possibility is a gene called PREP, not because depression is a preppie disease, but rather because it encodes prolyl endopeptidase, an enzyme that processes a class of mood-altering hormones in the brain.