Parsing out the genetic underpinnings of depression remains a challenge for researchers, despite the rise in the number of studies focusing on the human genome, the authors of a new scientific review article report.

The researchers behind the article, published in the January issue of the Harvard Review of Psychiatry, reviewed a number of studies on the genetic link to depression, which is described as one of the most prevalent, disabling and costly mental health conditions in the U.S. According to the Anxiety and Depression Association of America, about 14.8 million American adults (6.7 percent of the U.S. population) suffer from depression.

Depression is known to run in families, study authors Dunn et al. report, with studies involving twins suggesting that genetic factors are responsible for roughly 40 percent of the variation in population risk of depression. Given the genetic complexity of depression, however, even large genome-wide studies have found no consistent association between specific genetic attributes and depression. While multiple genes are thought to be involved in all mental health conditions, an even larger combination of specific genes are suspected to be involved in depression compared with other mental health conditions.

“Given the established heritability of depression, there is every reason to expect that increasingly well-powered studies will indeed identify [genetic] risk loci,” the authors write.

“The genetic and phenotypic complexity of depression, however, may mean that such successes will require samples on the order of tens of thousands of participants.”

The authors call for not just larger studies to help find a link, but also more research that takes into account the role of a person’s environment, in addition to genetics, in the risk of depression. Studies so far looking at both genetic and environmental factors “have thus far failed to provide clarity but have fueled plenty of debate,” the authors write. Environmental factors most often refer to stressful life events, either recently occurring in adulthood or more remote childhood events, such as neglect or abuse.

“Given the enormous burden of depression, identifying its genetic underpinnings may be essential to preventing the onset of this disorder and improving the lives of those who already suffer,” the authors conclude.

While a concrete genetic link to depression risk has proved elusive, how a person’s genetic makeup affects their response to antidepressants is clearer. Most medications used to treat depression are metabolized by just two liver enzymes: CYP2D6 and CYP2C19.

A patient’s genes are a major factor in determining how active these enzymes are in metabolizing these medications. If the drugs are metabolized too quickly, a patient likely won’t receive any benefits from the drug. Too slowly, and the medication could build up and cause adverse side effects.

The YouScript Personalized Prescribing System allows doctors to determine their patients’ unique ability to process medications and select the right drug at the right dose. Learn more on the YouScript website.

To learn more about resources available for those suffering from depression, visit the website of the National Alliance on Mental Illness.