Genes Impact Suspect Cortex Areas More as Youth Mature
Thickening of cortex areas implicated in mental illness shows increasing genetic influence as the brain develops in childhood and adolescence, NIMH researchers have found. These areas also happen to be the latest to evolve and the last to mature. The peak of genetic influence in these areas coincides with the typical age-of-onset of most mental disorders in late adolescence/early adulthood. The new findings may provide insight into the workings of gene-by-environment-by age interactions in the disorders, says Jay Giedd, M.D., of the NIMH Child Psychiatry Branch.
Jay Giedd, M.D., Eric Schmitt, Ph.D., NIMH - MRI movies
Cristophe Lenglet, Ph.D., U. Minnesota -- DSI brain image
Van Wedeen, M.D., Harvard/MGH - DSI Animation
Brain & Behavior Research Foundation - video clip
UCLA Laboratory of Neuro Imaging -- DSI animation from "Navigating the Connectome"
Jay Giedd, M.D: Twins are the best way to address nature/nurture questions. Identical twins, or monozygotic, share almost one hundred percent of their DNA. And fraternal twins, or dizygotic, share out about fifty percent. So by seeing how much more alike the identical twins are than non-identical, we can get a sense for how much the DNA matters for brain or behavior or all kinds of different variables. Of course, its not nature versus nurture. Its nature and nurture -- and the interaction between the two that's really the key. These days that's usually called G by E interactions -- G for genes and E for environment. But what this paper demonstrates is that we need to add a third component to the G and the E. And that third component is age. And what that means is that in order to understand the effect of a particular gene in a particular environment, we also need to know where that individual is in the course of their development. So it may not seem that surprising land that age would matter, but to actually identify the specific facts and figures about how this age by Jean by environment interaction (works) hasn't been all that easy, partly because we have to follow people over time as they go from a child to an adolescent to a young adult. And in and this case, the people have been identical or non-identical twins, but also their brothers and sisters. Genetically, they also I'll share fifty percent their genes. And over the past decade we followed about eight hundred people, having them come to the NIH at about two year intervals where we did a scan of their brain. We see how they're doing in school, in life, their behavior, their emotions, their cognition. And we see how these factors change over the course of development. The main thing that we found was that it's a moving target. So which parts of the brain are more or less heritable changes a lot as you go from a baby to it a child to a teenager to an adult. And so what we've been able to do with these movies that you're seeing is to actually demonstrate the specifics of these changes. And what we see here are the areas in red other areas in the brain that are most charitable. And what we see is that it's not a one-size-fits-all. That certain parts of the brain become more heritable during adolescence. Other parts are more heritable in your early childhood, others in in middle ages. And why we think this is important is that the same brain areas that are changing in heritability during adolescence are also the parts for the brain that we acquired most recently in our evolutionary history and also they're the parts of the brain that are involved in illnesses that happen during adolescence. This has been one of the big mysteries in psychiatry. Why do things happen when they do? For a genetic illness like schizophrenia, you're born with those genes. You're born with those risks. So why doesn't it manifest when it does? Until late adolescence or young adulthood. This has always been one of the big research questions for us. And now we think we might have some insight into that. Because one way of looking at this is that the reason these brain parts get more heritable during adolescence is because they get expressed then. That if they're not being expressed any younger it doesn't matter if you're identical or non-identical, because those genes aren't doing anything. But whether it's puberty or other unknown timing factors, when these genes then become expressed, those parts for the brain become more heritable. But if this process goes awry, then it also may be why these illnesses are unleashed when they happen. Most illnesses actually manifest during adolescence -- psychosis, bipolar disorder, eating disorders, substance abuse, anxiety, panic attacks. So literally over fifty percent of mental illnesses when they happen occur during this adolescent period. And we're particularly interested in these parts of the brain that become more red during late adolescence, when many of the illnesses are emerging. And they're parts of the brain that we've acquired most recently in our evolutionary history -- so the most difference between us and chimpanzees and bonobos. So its all is converging upon this common story -- the things that take the longest to develop also have genetic factors that impact later and later in life. So the next step for us now will be to really try to explore this link between the illnesses that have their onset during this time and the typical brain changes possibly driven by the same underlying genes. At one age this particular gene might affect this particular brain in this way, and at a different age no effect -- or even an opposite effect. And so I think the whole field will be affected by these sort of findings, in terms of really trying to introduce age into the G by E interaction question.