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Dr. Daniel Pine, a psychiatrist, directs the research program on mood and anxiety disorders of children and adolescents at the National Institute of Mental Health in Bethesda, Md. The research seeks to identify the genetic and environmental factors underlying these mental illnesses so clinicians can identify who might be prone to them, spot early symptoms and tailor treatments more precisely to individual patients.

Q: What is the difference between an anxiety disorder and anxiety that is an appropriate response to an uncomfortable or threatening situation?
A: The easiest way to differentiate between these two responses is to talk about the concept of impairment. The idea behind impairment is that the person’s anxiety interferes with his or her ability to do something. The feelings of anxiousness prevent that person from doing something that other people in the same situation could do, leading to avoidance. In other words, the anxiety prevents the individuals from going places or doing things that they would like to do.
For example, everybody has some degree of anxiety in social situations. But we think of it as a disorder when the anxiety is so extreme that the person would refuse to do presentations at work or would refuse to go to parties or would not talk in public places where one is obligated to talk — for example, ordering a meal in a restaurant or requesting a book from a librarian. This is the easiest way to distinguish between normal and abnormal anxiety.

Q: So if one is able to manage these everyday tasks, they’re O.K.?
A: Not exactly. There are different manifestations of anxiety disorders that complicate this simple explanation. Some people manage these tasks but with such an extreme level of anxiety that we still classify it as a form of anxiety disorder.
Let’s think about the person who is extremely shy in social situations. They may go to work or go to a party or order in a restaurant or talk to the librarian. But they will be absolutely miserable while doing it. They will have a great number of physiological symptoms — rapid heart beat, sweating, butterflies in their stomach — and extreme stress in anticipation of doing any of these things.
So with anxiety disorders, it is not a simple yes-no set of symptoms or laboratory results as you might have with, say, diabetes. The diagnosis of abnormal anxiety rests on a mental health professional’s judgment that the level of distress experienced by the individual, relative to all other people in that situation, is extreme.

Q: How early in life can anxiety disorders develop?
A: Anxiety is similar to many mental disorders in that symptoms often emerge during childhood and adolescence. But it is also extremely common for children and adolescents to, at various times, exhibit high levels of anxiety without that signifying an anxiety disorder.
Somewhere between 10 percent and 20 percent of children and adolescents will have transient anxiety at some time during their development. And of these youngsters, more than half will grow up and mature to be fine. They will not have problems with anxiety or other mental illness in adulthood. On the other hand, among anxious children and adolescents, those with continuing anxiety will grow up to account for the majority of adults with anxiety disorders and with depression.

Q: So in some children, early anxiety — say, difficulty leaving home to go to school each day — could be an early sign of a developing, life-long mental illness like depression?
A: Yes, but it is important to emphasize that most children with anxiety will do fine when they are followed over time. We can’t predict at the moment which child’s anxiety will resolve and which child’s will lead to chronic illness, but we are working through research to try to understand that better. When we do, it will have a major impact on how we think about children and also how we think about adults with chronic mood and anxiety disorders, since we believe the roots of these illnesses are found in childhood.

Q: Does this suggest a genetic basis for anxiety disorders?
A: Only to a degree. Most chronic mental illnesses appear to be complex mixes of many different genes and many different environmental effects. We’re just beginning to understand how all of these things go together. We know that it’s rarely one thing that gives rise to a mental disorder, and we know that different mental disorders have different mixes of genetic and environmental influences.
Compared with bipolar disorder or autism, for example, anxiety disorders are more strongly related to environmental influences. That does not mean that there isn’t a genetic component — we believe there is a significant genetic component — but it’s probably in the minority of factors that account for individual differences. In autism or bipolar disorder, the genetic influence is well over 50 percent — probably upwards of 80 percent in terms of what ultimately accounts for the syndrome. In anxiety disorder, it’s only 30 percent to 40 percent; the remaining 60 percent to 70 percent of influences are environmental, meaning what happens to the child or the adult in their daily life.

Q: In bipolar disorder and schizophrenia, brain imaging studies have shown significant differences in brain development during adolescence. What is unusual in the brains of people suffering from anxiety disorders?
A: There is particular interest in the function of the amygdala, because we know from studies of primates and rodents that this area of the brain is very important in terms of understanding how organisms react to danger and how individuals differ in their fear response. It turns out that when presented with subtle signs of danger, the amygdala of kids with anxiety and kids with depression react similarly to the amygdala of currently healthy kids who are at risk for anxiety and depression.

Q: So the amygdala is more reactive in these children than in healthy children without symptoms of or risk factors for anxiety?
A: That is correct.

Q: We commonly think of adolescence as the period when many psychiatric disorders emerge. Are anxiety disorders likely to appear earlier in a child’s development?
A: Without question. In fact, there is some thought that we can see the early signs of risk for anxiety in the temperamental profile of young children. There is, for example, a temperamental type called behavioral inhibition. This refers to a 2- to 3-year-old child who exhibits a tendency to be very wary, withdrawn and shy in new situations, especially socially. We don’t think of behavioral inhibition as an anxiety disorder because it doesn’t interfere with function. On the other hand, when we follow these children over time, we find that a much higher percentage of them grow up to have clinically significant anxiety compared with children who are not of this temperamental type.

Q: But not all toddlers with behavioral inhibition grow up to have anxiety disorders?
A: Not at all. One of the things to keep in mind is that children are very resilient. Most children with behavioral inhibition or early anxiety symptoms will not develop clinical problems. But of the adolescents who have persistent problems with anxiety, many will have had signs or seeds of those problems in earlier years.
Where to draw the boundary between a risk factor for a problem and a clinically significant problem is frequently debated, especially when new research comes to light. It is similar to the way definitions of hypertension shifted in the face of new information about what happens to people with differing levels of blood pressure. It used to be that a blood pressure of 85 was considered borderline. Then researchers found that people with a blood pressure of 85 were, in fact, at risk for some bad things, which led to lowering the level at which patients were considered borderline. A similar thing is going on now in how we think about development and risk for anxiety disorders. There is clearly a gray zone in terms of identifying factors that put children at risk, but perhaps not so high a risk that we would think of it as evidence of a clinical syndrome.
This is really where the research on brain function comes in. As we understand better the way in which differences in brain function relate to differences in behavior, the hope is we’ll have a much better sense of what’s going to happen to this individual or that individual over time. In this way we hope to do for psychology and psychiatry what other medical breakthroughs of the 20th century did for cardiology and neurology.

Q. What impact does research have on the care of people with anxiety?
A: Understanding what takes place in the brain helps us think of new ways to treat symptoms. For example, until about five years ago, everyone, including myself, thought of anxiety disorders as reactivity disorders: the brains of people with anxiety were unusually sensitive to danger and tended to overreact. There is some data to support this, but as we did more research we noticed that the biggest differences between anxiety patients and healthy people were not found in their response to extreme, obvious danger but rather in their brains’ reactions to subtle threats or ambiguous situations.

This finding suggests that the root problem is one of telling the difference between a potential threat and a real one. And this, in turn, suggests that anxiety results from a learning disorder rather than a reactivity disorder. When we look at anxiety this way, we are led to a host of potential new treatments geared toward correcting a learning deficit. This has treatment implications for both children and adults. The hope is that we will eventually be able to determine which patients will benefit from therapy or from medication and which need a combination of therapy and medication.
Publish date: 7/11/2008


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