Depression: Here’s a gene that may make some folks more susceptible

Depression strikes a huge number of Americans at one time or another of their lives -- and studies show that genes are involved in susceptibility to this awful “Black Dog,” as Winston Churchill used to term his struggle with the mood disorder.

But what are the genes involved? A study in the journal Archives of General Psychiatry implicates one. It directs the formation of a small peptide in our brains, Neuropeptide Y.

Neuropeptide Y is found all over the place in our brains, and prior studies had shown that the levels in our bloodstreams and spinal fluid seem to correlate with how resilient we are to life’s stresses: the more NPY, the more resilient.

Data like these led Dr. Brian Mickey of the University of Michigan and colleagues to test whether people who had different versions of the Neuropeptide Y gene scored differently in a few tests linked to depression and stress. Some of the participants (181 total, 44 with a diagnosis of major depression and 137 without one) had a version of the gene that’s known to cause higher levels of NPY in the body. Others had versions that result in lower levels of NPY. (Still others had a gene variant that led to intermediate levels of NPY.)


Here’s what the scientists found:

1) When participants were given a list of depressing words to read, the brains of those who had a low-NPY gene became more active, on average, in two regions known to be associated with depression: the medial prefrontal cortex and the rostral anterior cingulated cortex. It looked rather as if the low-NPY group were less resilient to the negative effects of the words on mood.

2) When participants were given a nasty pain test (an injection of saline into a muscle that resulted in pretty extreme pain for 20 minutes -- and yes, subjects gave permission and the whole experiment was vetted by a review board at the university) those with low-NPY levels said they felt more pain than those who had higher-NPY levels. Pain isn’t exactly the same as depression, but pain is definitely stress-inducing, and how we react to life’s stresses is certainly linked to a person’s propensity for depression.

3) Some of the people in the experiment were diagnosed with major depression; others were not. The scientists looked at the kind of NPY gene each person carried and found that those who were depressed were statistically more likely to have a low-NPY gene variant than those who were part of the “healthy” control group.


The scientists say these findings fit well with previous NPY-depression results — and further strengthen the link. And, they add, this is more than just interesting from a “what causes depression?” point of view. There may be practical applications one day. Anyone who’s had experience using an antidepressant knows that it takes trial and error to find a med that works. If studies like this -- as the authors are suggesting -- could begin to divide people into groups that might fare better with one type of antidepressant drug versus another, that would be good news for a lot of patients and a lot of psychiatrists.

But that’s for the future. And as the authors point out, it’ll take more research to move these results beyond what they are now -- suggestive correlations -- to a more concrete link between proneness to depression and Neuropeptide Y.

Here’s a short related item on how hard it can be to pin down links between genes and susceptibility to depression.

And here’s the new Neuropeptide Y study. (The journal only lets you read the abstract unless you want to pay.)