By SARA TRACE & STEPHANIE ZERWAS
Published: September 17, 2013

Together with Dr. Pat Sullivan, Director of the Center for Psychiatric Genomics, we recently published a paper entitled “Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa.” Don’t let the title scare you off—the findings are actually pretty straightforward.

One of the goals driving this research is to identify biomarkers for eating disorders. A biomarker is exactly what the name implies, a biological marker. It can be any measurable characteristic that is associated with a condition or disease. For example, when you go to the doctor for a physical, they take your blood and check your LDL levels as biomarker for cholesterol. Biomarkers are important because they measure disease severity, progress, and whether a treatment is working. For example, if your LDL levels decrease after you start a statin drug, you know the drug is working as it should and your cholesterol is improving. 

Unfortunately, for many psychiatric conditions including anorexia nervosa, there are very few biomarkers. For example, there’s no “blood test” that allows you to diagnose anorexia nervosa or to determine whether treatment is working. One of the tricky things about measuring biomarkers for anorexia nervosa is that it’s hard to disentangle whether the biological changes that we see are simply effects of starvation or if they are biological markers that are indices of the illness. Ultimately, our goal is to figure out how to separate out biological indices of starvation from those of disease.

For this study, we examined whether gene expression level could be a meaningful biomarker for anorexia nervosa. Flash back to high school biology class for a minute. You have DNA (your genetic blueprint) in all of your cells. DNA programs messenger RNA (or mRNA). That mRNA goes around and tells your cells to make proteins that are critical for your tissues and organs to function properly.

How much your genes are expressed (measured by levels of mRNA) can vary widely, particularly when you are sick or have other medical problems. Think of your DNA like a recording studio. What you end up hearing on the radio is rarely what things actually sounded like in the studio. The mix artist might dial up the bass, edit out some vocals, dial down the saxophone. This is sort of like gene expression. The person doing the mixing is determining which genes are being expressed. The bass, the sax, the vocals were all there, but some are turned on, some off, some up, and some down.  Developments in gene technology called RNA sequencing mean that we now have the ability to examine gene expression changes across a very large number of genes.

Our goal in this study was to understand how gene expression (mRNA levels) change as individuals receive treatment for anorexia nervosa and undergo renourishment. We invited six women from the inpatient eating disorders unit at UNC to donate a blood sample at the beginning of their inpatient treatment and again at the end of their treatment. We measured their mRNA levels and compared them before and after.

We found that four genes were down regulated after treatment. They were dialed down or had lower levels of gene expression (less mRNA) at the end of treatment. Several of these genes we know very little about and it’s difficult to guess how their regulation might be involved in anorexia nervosa recovery.

We also found that four genes were upregulated at the end of treatment. They were dialed up or had higher levels of gene expression (higher levels of mRNA). Interestingly, all of these genes (OR52J3, OR51L1, OR51A4, and OR512) are involved in sense of smell. This was pretty fascinating and a little puzzling. Some researchers have found that when individuals are struggling with anorexia, their sense of smell suffers and it’s hard for them to distinguish between smells. Our data suggests as people recover from anorexia nervosa, these four genes are increasingly expressed.  Smell plays an important role in taste, in how rewarding or aversive food is, and in signaling hunger or fullness. Our data definitely point to the need for additional research to understand how sense of smell may contribute to or perpetuate anorexia nervosa, whether genes involved in smell could be biomarkers of recovery or whether there is a way to integrate smell into treatment for anorexia nervosa.

This was just a pilot study. The amazing advances in gene technology pointed us in some interesting new directions. We are so grateful to the women who participated in the study for rolling up their sleeves and helping begin our exploration into gene expression. Guided by our data, we hope to continue to research ways to assess biomarkers for anorexia nervosa and to use this information to inform new treatments.

Kim Y, Trace SE, Crowley JJ, Brownley KA, Hamer RM, Pisetsky DS, Sullivan PF, Bulik CM., (2013) Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa. Psychiatry Res.  Jun 15