|
||||||||
|
PSYCHIATRY Deciphering the Adolescent BrainFindings Are Toppling Old Views, Stoking Old Controversies About Brain's Coming of Age Adolescence may come in like a lion, bringing reactions and moods so snarly and ferocious that kids and parents may wonder what hit them. For an unfortunate few, it can mean the beginning of even more disturbing behavior. Schizophrenia, with its delusions, hallucinations, and jumbled thoughts, tends to strike in the teen years. Brain researchers have wondered why the onset of puberty presages such turbulence, both for healthy kids and those affected by schizophrenia and other psychiatric disorders. McLean scientists Martin Teicher and Deborah Yurgelun-Todd are, in independent studies, turning up paradigm-rattling clues. Their findings, which derive in part from new methods of imaging the brain, are also helping to resolve old controversies about the brain in the tender years prior to adulthood. How does experience shape the young brain and for how long? Can negative experiences, such as sexual and physical abuse, actually cause brain damage? Are psychiatric disorders such as attention deficit– hyperactivity disorder (ADHD) the function of brain abnormalities? Is there such a thing as "normal" adolescent brain development?
Ongoing research by Martin Teicher (left) and Deborah Yurgelun-Todd suggests that the adolescent brain is far more dynamic and more susceptible to the effects of experience than previously thought. A tenet of neurobiology, and one unchallenged until recently, holds that the brain finishes most of its growing by puberty, at which point it settles more or less into its adult form. It now appears that the adolescent brain is far less finished, and far more dynamic, than previously believed. Just as adolescents exhibit growth spurts—one moment the face appears all eyes, the next all nose—various features of their brains are undergoing dramatic changes. At various times during childhood and into adolescence, a welter of new synapses is made and then whittled down, producing mature brain structures. Not all parts of the brain undergo this proliferation and pruning process, nor does it happen in all individuals equally. Teicher, who is HMS associate professor of psychiatry, has been following where, how, and in whom it occurs, a venture he believes could hold the key to a better understanding of normal and abnormal brain development. Much of his work has focused on the prefrontal cortex and striatum. Both receive projections from the dopamine system and are thought to play a role in schizophrenia. Working with rats, he and colleagues looked at the timing of overproduction and pruning of dopamine receptors, which provide synaptic contacts, and observed a suggestive pattern. Proliferation began at the human equivalent of five to seven years of age, peaked at puberty, and reversed by early adolescence—right around the time kids become vulnerable to schizophrenia. Teicher believes that this stripping away of connections, which normally results in more finely tuned and effective circuits, could be unmasking a congenital defect in people with schizophrenia. But he has evidence that the drama occurring in the striatum may be at work in other psychiatric disorders, most notably ADHD and Tourette syndrome. In contrast to schizophrenia, both of these disorders appear in childhood and often wane in adolescence. They also occur more often in boys than girls. Teicher and his colleagues have recently found that the timing of proliferation and pruning in the striatum of rats closely matches the rise and fall of Tourette's and ADHD symptoms. And the pruning pattern is much more pronounced in male rats than females. The News Today"So there is good news and bad news. Some disorders may benefit from pruning. For example, it may suppress the restlessness of ADHD or the tics you find in Tourette's. But it also may lead to manifestations that had been protected by overproduction," says Teicher.The news may also be mixed when it comes to "normal" adolescents. What the pruning work suggests is that the brains of teens are different from, and presumably less mature, than the brains of adults. Yurgelun-Todd, who is HMS assistant professor of psychology in the Department of Psychiatry, and her colleagues have conducted a series of imaging experiments which suggest, at the very least, that adolescents may be using their brains differently from adults. The researchers asked 16 normal adolescents between the ages of 11 and 17 to complete two tasks while having their brains scanned using functional magnetic resonance imaging (fMRI), which records brain activity. In one task, they were shown pictures of people with fearful expressions and asked to say what emotion was being expressed. In another they were asked to complete a number of word-production tasks. Adults, when faced with the same tasks in a previous set of experiments, exhibited activity primarily in their frontal lobes, and to a much lesser extent in the temporal lobes. The adolescents, especially the younger ones, exhibited a much different pattern of brain activation. For example, during the affect discrimination task, they relied much less on their frontal lobes—the seat of goal-oriented rational thinking—and more on the amygdala, a structure in the temporal lobes known to be involved in discriminating fear and other emotions. They also made more mistakes. Kids under the age of 14 often characterized the facial expressions as sad, angry, or confused rather than fearful. Older teenagers answered correctly more often and exhibited a progressive shift of activity from the amygdala to the frontal lobes. It is not yet clear whether the frontal lobes are less well developed or just being used in a different way in the younger adolescents. Yurgelun-Todd has been experimenting with a new method, functional magnetic resonance spectroscopy, to identify the chemical content of small regions of brain tissue. Her preliminary results suggest that different tissues do, in fact, change their chemistry as adolescents get older. She is currently extending her imaging studies to a much larger population of 200 subjects. While most are normal, the sample also includes adolescents with schizophrenia, bipolar disorder, depression, and frequent marijuana use. So far, it looks like what is true of young adolescents—reduced frontal activation and fewer correct answers on the affect discrimination test—is also true of many older teens with these disorders, but the reasons are unclear. The Moral of the Story"Is it that some of our patients are unable to learn for biological reasons or is it that they weren't given the right environment?" she asks. Taken together, the findings of Teicher and Yurgelun-Todd suggest that the question is not an either–or proposition. "It's by no means simple. Your experiences are going to affect your hardware," says Teicher.On the one hand, the message sounds optimistic. "If it turns out we're not hard-wired for discriminating different types of affects, then experience with social interaction may help develop that skill. This means we may be able to improve those functions," says Yurgelun-Todd. "We have so often assumed that this will take care of itself—we'll teach math, we'll teach science and linguistics but, of course, you'll all learn to get along." But the demonstrated malleability of the adolescent brain has more disturbing implications. It suggests that sexual and physical abuse and other traumas experienced during childhood and adolescence can produce lifelong alterations in brain structure. Most people accept that such practices inflict deep psychological wounds but until recently few considered the possibility that they might damage brain tissue. In a study published several years ago, Teicher and his colleagues showed that adults who had experienced physical or sexual abuse, or both, before the age of 18 were much more likely to exhibit olfactory hallucinations, visual disturbances, and feelings of déjà vu or jamais vu (familiar situations seeming unfamiliar)—symptoms found in temporal lobe epilepsy and associated with abnormal limbic system activity. Using EEG and MRI techniques, he has documented the traces that abuse can leave in the brain of an adult. He has found changes in the left hemisphere of the brain as well as in particular structures, such as the corpus callosum, the band of fibers connecting the two halves of the brain, and the cerebellar vermis, an esoteric structure of the cerebellum. Interestingly, the latter region is very sensitive to elevated levels of stress hormones, particularly the glucocorticoids. Teicher is currently looking at the effects of verbal abuse—being repeatedly scolded, criticized, yelled at—on the developing brain. "Patients will often tell you that 'what they said to me left deeper wounds than their hitting me,'" he says. His preliminary results suggest verbal abuse has enormous effects on the limbic system, most likely through stress pathways. "When someone's calling you an idiot, or whatever, you're going to have a tremendous emotional response. But you can also replay it. You can keep on stressing yourself over and over the same way," he says. "I don't think society has a clue as to the severity of verbal aggression. It's a huge factor. You don't have to lay a hand on anybody at all," he says. "We need to really have our awareness raised about that—to show that it has potentially enduring biological effects." —Misia Landau An Atlas to Chart the Brain's GrowthIn what might be called a cartographer's dream, HMS researchers are joining with researchers from institutions around the continent to map the healthy human brain as it develops from birth through adolescence. Over the course of the next six years, they will be imaging the brains of over 500 children and adolescents. Each of the subjects, ranging in age from birth to 18 years, will undergo structural magnetic resonance imaging (MRI) and two other imaging modalities and take a series of psychological tests three times during the study. By project's end, the researchers hope to produce a series of MRI atlases documenting not only average shapes and sizes but also the variation exhibited by the brain and its individual structures. "So we would have a growth curve for each brain structure surrounded by an envelope of variability," says Nick Lange, HMS associate professor of psychiatry (biostatistics) at McLean Hospital. The atlases would provide a valuable tool for both basic researchers and clinicians, "similar to what a growth chart would be used for by a general practitioner wanting to look at how Johnny is growing," he says. Subjects for the study, which is funded by the National Institutes of Mental Health, Neurological Disorders and Stroke, and Child Health and Human Development, are currently being recruited at seven sites around the country, including Children's Hospital in Boston. Data will be sent to the Montreal Neurological Institute for processing and then passed on to McLean, where it will undergo statistical analysis in Lange's lab. |
