Study: identifying genetic factors in depression poses special challenges

Jan. 9, 2015

Even with modern genomewide analysis techniques, it has proven difficult to identify genetic factors affecting risk for depression, according to a topical review in the January issue of Harvard Review of Psychiatry.

In recent years, techniques such as genome-wide association studies (GWAS) have accelerated efforts to identify the genetic factors underlying a wide range of diseases. But so far, GWAS of depression have found no associations. The limited success of GWAS in identifying depression-associated genetic variants is in contrast to the results for other psychiatric disorders. For example, studies have identified more than 100 genetic variants for schizophrenia and bipolar disorder. What's more, genetic factors previously suggested as contributors to depression risk—such as genes affecting dopamine or serotonin neurotransmission—haven't been confirmed.

Another issue is that GWAS have not as of yet accounted for the role of environment. Studies of gene-by-environment (GxE) look at how genes may modify the effect of environmental factors on depression risk (or vice versa).

A 2003 study suggested an interaction between a gene variant affecting serotonin and stressful life events—for example, childhood maltreatment. Thus far, studies have yielded conflicting results for GxE—while some studies supported this GxE effect, others showed no associations with the serotonin variant. However, other GxE studies have suggested more consistent associations for other genes, including genes involved in regulating the stress response.

The researchers think the combination of GWAS and GxE may help yield new insights. Study co-author Erin C. Dunn, ScD, MPH says that research on the genetics of depression is “at an exciting, yet challenging crossroad. Although the search to identify genes associated with depression has proven challenging, many scientists worldwide are working hard to identify its genetic underpinnings.”

Read the article at the Harvard Review of Psychiatry website