Genetic Origins of Depression

Genetic Origins of Depression

It's like hunting for a particular landmark on the horizon, says Sebastian Zöllner. "You look for a helpful marker." But in this case, the markers aren't mountains or lakes, they're genetic mileposts that indicate genes linked to depression, one of the most complex of psychiatric diseases.

Zöllner, an assistant professor of biostatistics with a joint appointment in the University of Michigan Department of Psychiatry, is searching for DNA fragments that may distinguish people who have depression from those who don't. It's a daunting task. Not only are there tens of thousands of genes in the human organism, making it prohibitively expensive to sequence a single human genome, but because depression is such a complex disease, it's impossible to pinpoint its precise cause. In addition to DNA, gender, age of onset, and environment can all contribute to depression.

Still, Zöllner and his colleagues in the UM Depression Center hope to identify specific fragments of the human genome that underlie the disease. (see Depression: The Public Health Dimensions).

Working with genetic marker information extracted from blood samples taken from a group of people who have depression and from a second group of people who do not, Zöllner is searching for genetic "landmarks" that tend to show up in individuals with depression more often than in individuals without the disease.

The landmarks themselves are not responsible for depression, Zöllner cautions, but the accompanying gene fragments--which are inherited together with the landmarks--may be.

He likens the process to getting directions to the home of someone who lives near a mountain: "The mountain isn't what you're looking for, but it shows you where to look."

Using a mathematical theory developed for population genetics, Zöllner is modeling the process of how these DNA fragments are inherited through many generations. "The hope is that I can tell my colleagues in the Depression Center, 'Here's a region, or maybe a gene, you ought to look at. Let's sequence that gene to see if there are any variants that can help explain depression.'" Those genetic variants may give researchers the tools they need to better diagnose depression and understand how the disease evolves.

If he and his colleagues are "really lucky," Zöllner says, "we'll find a gene that explains maybe five percent of depression cases." Even that, he adds, may take years. But Zöllner says the gene doesn't need to explain a lot of cases in order to teach scientists a great deal about depression.

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The gene doesn’t need to explain a lot of cases in order to teach scientists a great deal about depression.