So I'm going to call this, Stress and Diathesis, and you'll see why. So we have a case control study that I have already presented to you from George Brown and Tirril Harris, called, The Social Origins of Depression, it's a book by Brown and Harris. And I presented two of the three columns to you last time, to be clear about the case control study. I presented the middle and right most column. But I want to make a little bit of a point about this. And that is the, it turns out you'll see, later in the course, in the lectures by Ramin Mojtabi that many cases of depression are basically never treated. They do not get into treatment their entire lives. If we study just patients, that's the left-hand column, as George Brown did, we worry that the patients are different from the general population, who may have depressive disorder also. So, Brown compared cases from poor patients to controls, from the survey, he also, in the survey identified cases from the survey. So you can say, the 68 versus 20 is the figure we looked at before, but it's not very different from the patient cases, 61 percent have a severe event. And so, this again is showing us that life events are associated with onset of depression and we can remember the story of Debra who suffered through the Buffalo creek flood from the first lecture and she more or less recited the the diagnostic criteria for depressive disorder. And we do not think that Deborah's depressive disorder was caused by inheritance. We imagine it was caused by the Buffalo Creek flood. Now, let's consider these two things interacting and this is from Ken Kendler's population based twin registry, and so we have the twin pairs graded as to the density of their risk for depressive disorder. So for example if we have a dizygotic twin we're sharing 50% of the gene with that twin. And that twin is normal, we have the lowest risk for depressive disorder in terms of inheritance. And, likewise, if the monozygotic co-twin is normal, we have a low risk for depressive disorders. If the dizygotic twin is a case of depressive disorder, then we are at higher risk for depressive disorder from our inheritance. And, likewise, if the monozygotic twin is a case, we are at even higher risk for a disorder. So, now consider that grading of a risk through genetics in interaction with whether there has been a life event prior to the month of onset. And you can see, if there's no life event, there's not much depressive disorder. It's the life event that potentaties the genetic mechanism and spreads people out according to their genetic risks. So, this is an example of a gene environment interaction. And the highest risk, you can see, about 14% of genetically dense or risky sample who have had a life event have an onset of depressive disorder. That's a high percentage to have an onset. Now, let's consider one other possibility. What's happening is we're getting more and more complex in terms of our methodolgy. I presented to you the case control, and the cohort study, and the ecologic study, as in a way kind of pure types. But we use that language, and that conceptual basis to study lots of different situations of data collection. And one of the most important of these situations is simply a general population survey. And this is a particular general population survey as it happens, of, of twins, but I'll show you lots of data below, of general population surveys. And I'll be using the term incidence sometimes, and that brings the cohort concept into play, that's a prospective study, and sometimes I'll be using the word prevalence, or association. And that brings the case control logic into play, which is the retrospective logic. Here is a personality trait, called neutroticism, this is a well studied trait, and neuroticism is the tendency that an individual has to react strongly to stress. So, it means people get anxious or moody or distressed or upset in the context of stress. Some people do more, we know this, some people are calm in the face of stress and some people are all anxious and upset in the face of stress. So we measure that trait, neuroticism, then we look forward in time. To people who have more neuroticism, or less neuroticism. And we consider stressful life events in that context. So if you look on the left hand chart, that's the males, and you can see that some of those males, the orange triangles, and the orange bar, have very high neuroticism. And they are much more likely to have an episode of depression in the future. In other words the trade is measured at one point in time and they have incidents of depression after that point in time. That's the cohort logic. And so you can see that the orange bar is higher than the red and, and blue and green bars. And that means that neuroticism is related to onset of depression. But you can also see that it's interacting with stressful life events. So, people who have a severe life event and a life event that's rated as severely upsetting to their life plans and the meaning of their life, those people have the most likely possibility of having an episode of depressive disorder. And so as you move from left to right the stress of the life event gets from none or minor to severe and their risk for depression goes up and this is true for males and females. And one final note about males and females. Again we see females have slightly higher risk for depressive disorder at any given level of neuroticism, and at any given level of stressful life events, the females are more likely to have an episode of depressive disorder. So, this leads us into, this is a conceptualization of these data, called the Diathesis Stress Model, this is a drawing by me, a redrawing of a model that was first drawn by Joe Zuben. So, many decades ago, this one is in color and it's prettier, but it's actually showing the way in which genes interact with stress. This is something I've shown you a couple of times, just now, in the slides. What we have is, we have some people with very few genes for a depressive disorder. Or a very low genetic loading for depressive disorder and those people can tolerate lots of stress. Even very high levels of stress they will not have an episode of depressive disorder so we think of for example and John McCain in the prison in north Vietnam he was possibly resistant. To having an episode of depressive disorder, possibly because of his genetic makeup. And we have some people who have many genes for depressive disorder, but they live in a good environment. Somehow their environment is protected, and so we can think the even though they're heavily loaded for the inheritance of depressive disorder, the environment doesn't produce it in them. So, this is an additive interaction of genes and stress. And you can see there, somewhere along the way, there is a boundary of diagnosis. And as we move up toward the upper right corner we get more genes, more stress. Any combination, but more of them are likely to have a more severe episode of, of depressive disorder. So in this section we're studying, basically, the way genes and stress interact. And those are the two most important aspects of depression as I told you in the first lecture.
