Biomarker for depression?

This week Cambridge researchers identified the first biomarker for major, or clinical, depression. This 'biological signpost' could mean boys at greatest risk of depression are diagnosed earlier.

Chris Smith spoke to Professor Ian Goodyer who led the study...

Ian - Clinical depressions are a whole group of as yet, poorly understood conditions, they emerge in the teenage years in the main. Between 13 and 17 years of age, about 1 in 6 to 1 in 10 of young people are going to experience depressions and about 30% of those are going to be quite severe, taking you to hospitals, GPs and in some cases, to psychiatrists and mental health specialists.

Chris - It's a very large number.

Ian - It is a large number. But there are many different kinds of illnesses in there. Some of them will only last for a few days or weeks. Unfortunately, some of them will last for many years and very occasionally, for the rest of your life. What we don't know is how to spot individuals in the community at large who would be at different types of risks for different kinds of depressions. People have been trying for some time - perhaps up to 30 years - to find markers in individuals that put them at risk for one or more of these kinds of depressions.

Chris - I presume, if you have some kind of marker then you can put people into a different category and different categories are going to require different treatments or interventions, and have different prognoses attached to them.

Ian - It would be the aim and objective to get to the kind of paragraph you just summarised. If we can find markers, does that allow us to identify groups at differential risks? Does that mean we can plan different kinds of interventions at the public mental health level? Or indeed, as you implied, at the clinical intervention level? Long way to go, but it's about time we started going down this path.

Chris - So, have you done this?

Ian - Well, for many years, we've known that the HPA axis - that's shorthand for the hypothalamic pituitary adrenal axis - releases a hormone called cortisol which moves up and down at different times of demand on the individual. It's a very important hormone. It's got nothing to do with disease. We need it to stay alive and it gets into all of our cells all over the place including the brain. About 40 years ago or so, some scientists in the states and in Europe showed that some individuals who were depressed had very high cortisols. At first, it was thought, well, this is just a consequence of being ill like having a high temperature. I think the initial excitement died off. But in the last 20 years, people have noticed that morning cortisol levels can be high in some individuals in the population at large who are not ill. That's intriguing. So, we started off over 2 decades ago in trying to figure out if high morning levels on their own were associated with the subsequent increase in onset of any kind of depression. The answer was yes.

Chris - Were you looking at blood or urine levels for that?

Ian - Well, we had to do the usual technical work. First, we had to develop an assay that was sensitive and specific enough in the lab. We then had to show that levels in different bodily compartments were correlated with each other. So, we did a study comparing CSF blood and saliva levels in different populations and showed that the levels in saliva were estimable with respect to blood which was estimable with respect to the CSF levels.

Chris - CSF is cerebrospinal fluid around the brain.

Ian - Yeah, the fluid around the brain. What that meant was that we could take saliva levels in the population at large and make some degree of interpretation about its implications for the brain. Now, that took 2 decades and then the study that we just published in the Proceedings of the National Academy of Sciences and funded by the Wellcome Trust, that took a decade. So, we needed approximately 1850 teenagers in two slightly different studies. The second thing we needed which has not been done before was, we needed to do this longitudinally.

Chris - So, you need to know, does one beget the other subsequently. If we have one at one point in time, do you then get the depression or the other illness later?

Ian - That's right. There's a bit of important mathematics because you have to try and establish longitudinally over 12 to 36 months, the relationships between depressive symptoms themselves and the relationships between different cortisol levels themselves. Then you have to put the two together. And that's how you create different classes in the population at large.

Chris - What have you found?

Ian - So, about 17% of the teenage population had both high long term depressive symptoms. Not clinical, just the kinds of things you and I were talking about and high long term morning cortisol levels. So, when you were in the group with the high depression, high cortisol level bit and you were a boy, not a girl - that's an interesting and slightly surprising finding. Then your chances of being depressed over the coming months, were about 14 times higher than either boys or girls in the rest of the population.

Chris - Which I presume means that we now have an opportunity to use this as some sort of screening test in order to identify people who might be at major risk.

Ian - Absolutely. It's ironic that about 25 years ago, GPs asked me if there'd ever be a screening test using cortisol. I said I wasn't sure. Well, here's our chance.