Neuroimaging Suggests Relationship Between Temperament and Social Anxiety Disorder

BOSTON—Children with inhibited behavior in early childhood showed brain differences on fMRI in a longitudinal study, indicating that temperament in early childhood may be implicated in the development of social anxiety disorder in adolescence and adulthood, reported Carl Schwartz, MD, at the 54th Annual Meeting of the American Academy of Child and Adolescent Psychiatry.

Thirty years ago, Jerome Kagan, PhD, observed 2-year-old children and classified them as having either inhibited or uninhibited temperament. Signs of behavioral inhibition included long latencies to play or interact with unfamiliar people or objects, long time spent proximal to the mother, and sensation of play or vocalization whenever a novel or unfamiliar person or object entered the room. These behavioral differences were also accompanied by physiological differences. For example, inhibited children had faster heartbeats and less beat-to-beat variability, and their pupils were more widely dilated when trying to solve cognitive problems. In addition, they had a greater decrease in vocal perturbation when words were spoken under stress, and they had higher levels of salivary cortisol.

About 10 years later, Dr. Schwartz contacted Dr. Kagan to ask if he could follow up on these children. “I became interested in trying to really look at whether the brains of these children might be different in some way and whether behavioral differences still existed,” explained Dr. Schwartz, Director of the Developmental Neuroimaging and Psychopathology Research Lab at Massachusetts General Hospital in Boston.
After interviewing the children blindly, Dr. Schwartz found that a third of the group who had been inhibited at age 2 had developed generalized social anxiety disorder at age 13.

“Two-thirds of the inhibited kids were doing well. It said something about either parenting, environment, genetic variability, risk, or resilience,” he said. In contrast, among the group who had been uninhibited, virtually none had developed social anxiety disorder. The very few children from the “low risk” uninhibited group who nonetheless developed social phobia had had severe abuse or trauma in their lives.

According to Dr. Schwartz, inhibited children at age 2 talked and smiled less frequently than did uninhibited kids, and these differences could still be seen at age 13. When the researchers conducted a Stroop interference test, they found that the inhibited children seemed to have more of a delay—or more of a “Stroop effect”—when presented with words that had symbolic meaning of threat, compared with the uninhibited children. Physiologic differences in heart rate and blood pressure were still noticeable as well.

DIFFERENTIATING INHIBITED FROM UNINHIBITED BEHAVIOR

Dr. Schwartz hypothesized that fMRI studies of amygdala reactivity to novelty would reveal brain differences relating to temperament. “At the time we did this study, no study had actually shown with fMRI that the amygdala could be activated with neutral faces that were familiar, as opposed to unfamiliar,” said Dr. Schwartz. “So we did a very simple experiment. We took a large set of pictures of people and showed a subset of them over and over in the brain scanner to make them familiar. We then showed faces of people that had not been shown before, mixed in with the faces that had been shown repetitively, and compared the signal coming from the amygdala during the two types of faces,” he explained.

The study involved a small group from the earlier study—13 inhibited and nine uninhibited patients—who were now in their early 20s. Results showed that the amygdala was more reactive to novelty in the inhibited patients than in the uninhibited subjects, demonstrating that some brain differences relating to temperament are preserved from infancy into early adulthood.

FROM TEMPERAMENT TO DISORDER

Among those who participated in the neuroimaging study, two of the 13 inhibited patients had social anxiety disorder, compared with none of the uninhibited patients, and there were another two inhibited subjects with social anxiety disorder who were on psychiatric medications at the time of the study, requiring their imaging data to be excluded. This underlined the link demonstrated in the earlier study of 79 adolescents, reported Dr. Schwartz. So how does inhibited temperament lead to social anxiety disorder? He hypothesized that inhibited temperament may be a risk factor for generalized social anxiety disorder and that children may be born with a hyperreactive amygdala. If the prefrontal cortex—which evaluates and modulates the initial response of the amygdala to a stimulus of interest—fails to moderate input from a hyperactive amygdala, the amygdala will continue to be hyperactive, and a disorder might develop.

—Karen L. Spittler

Suggested Reading
Schwartz CE, Rauch SL. Temperament and its implications for neuroimaging of anxiety disorders. CNS Spectr. 2004;9(4):284-291.
Schwartz CE, Wright CI, Shin LM, et al. Inhibited and uninhibited infants “grown up”: adult amygdalar response to novelty. Science. 2003;300(5627):1952-1953.

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