Caroline Helwick

March 29, 2011

March 29, 2011 (New Orleans, Louisiana) — The amygdala and its role in emotional development appear to be especially vulnerable to early life stress, according to research presented here at the Anxiety Disorders Association of America 31st Annual Conference.

Nim Tottenham, PhD, of the Developmental Affective Neuroscience Laboratory at the University of California, Los Angeles, described findings from a study of 51 children adopted from orphanages, mainly in China, to US parents. Maternal deprivation, which obviously occurs as part of orphanage care, is a model of early postnatal adversity, she said.

"The species' expectation is that a primary caregiver will be present," she explained. In orphanages the ratio of caregivers to infants is often 1:20, and even in the best situations it is never less than 1:6, with rotating shifts. "This violates the species' expectation for care and is a potent stressor," she said.

Dr. Tottenham noted that infants reared in orphanages exhibit physical growth and behavioral delays, but "catch up" in these domains can be robust. On the other hand, socioemotional symptoms are more resistant to recovery, often persisting into adolescence after other concerns have faded.

Also worrisome is the fact that difficulties in social and emotional development can occur even in the absence of profound deprivation. This can lead to poor social attachments, emotional dysregulation, heightened anxiety, negativity bias, and more, she said.

Stress-Induced Changes

Less clear is the aspect of timing, she continued. "When does the environment have the biggest impact on the brain structure?"

This can be hard to discern because adversity can have a "messy" temporal course. An advantage of studying children who have experienced orphanage care and have subsequently been adopted is that "the period of that particular adversity is temporally discrete and the end date for the adversity is known," Dr. Tottenham noted.

"We were able, therefore, to examine the effects of timing of early-life stress on the developing emotional system, and we found evidence that long periods of orphanage care are associated with alterations in neuroanatomical development," she said.

Neurobiologically, the amygdala helps navigate the emotional environment, and its overactivity is associated with difficulty with emotion regulation and the development of anxiety disorders.

Furthermore, in the rat model, environmental manipulations — including handling, maternal separation, and low quality of care — have been shown to alter the development of the amygdala and hippocampus. Additionally, periods of rapid developmental change are associated with heightened vulnerability of brain regions to environmental exposures.

This background supports the hypothesis that early adversity in the form of lack of stable caregiving would lead to stress-induced changes in neurobiology, leading to hyperactivity of the amygdala, poor emotion regulation, and the development of anxiety and affect-related behaviors.

Exaggerated Responses

The study included 51 children (40 girls and 11 boys) adopted by the age of 2 years from orphanages in Asia (73%) or Eastern Europe (27%). Almost all had been placed in orphanages within the first year of life, and 80% were adopted by 2 years of age. The mean time in the orphanage was 15 months. At the time of the study, their mean age was 8 years and their mean IQ was 101. A matched control group included 42 children.

On neuroimaging, regional cortical volumes for the adopted children relative to controls were not significantly different. However, when children adopted early (<15 months of age) were distinguished from later adopted children (>15 months of age), differences emerged in amygdala volume, with older children having a significantly greater volume than those adopted earlier, even after controlling for IQ and the presence of anxiety disorders and after removing 1 outlier (P < .007), Dr. Tottenham reported.

Interestingly, larger amygdala volume was positively correlated with higher ratings of internalizing behaviors as measured by the Child Behavior Checklist (P < .004) and number of anxiety symptoms as measured by the SCARED inventory (Screen for Child Anxiety Related Emotional Disorders) (P < .03).

Further problems emerged on the emotional face go/no go paradigm, which measures self-regulation in emotional contexts. The accuracy of the children's answers was reduced in the setting of negative valence (eg, threatening faces), she reported.

"We think that highly arousing negative information disrupts the child's ability to regulate and the child has an exaggerated response to negative faces," she said.

Finally, the adoptees demonstrated diminished eye contact, both on an eye-tracking task and on live dyadic interaction. The amygdala activity also predicted the amount of eye contact, with less eye contact seen in children who had higher amygdala activity during the task.

The findings were replicated in a similar cohort of 55 children adopted by adults living in Los Angeles and 57 matched controls. In addition, for this cohort, scores on tests of generalized anxiety and panic were double those of the controls (P < .0001). Significant differences were also noted for social anxiety (P < .05) and separation anxiety (P < .01).

Sleep problems were also reported as major issues by the parents, and objective studies revealed the children were not different from controls in time spent in bed but had greatly reduced sleep efficiency. "Separation anxiety accounted for 36% of the variance in this analysis," she added.

Dr. Tottenham summarized her key findings:

Early postnatal adversity is associated with atypically large and hyperreactive amygdala during childhood, poor self-regulation in emotional contexts, and neural bias toward emotionally and away form perceptuo-cognitive processing;

The amygdala is a long-term mediator of early postnatal adversity and later behavior that governs social, emotional, and sleep behavior; and

The amygdala and its associated emotional development may be especially vulnerable to early-life stress.

Opportunity for Early Intervention

Bekh Bradley, PhD, assistant professor of psychiatry and behavioral sciences, Emory University, Atlanta, Georgia, applauded the investigators for being able to "separate out the trauma, pre and post.

"This was a nice design for the study. We can see what happens as a result of very early trauma, even once it has been corrected," he noted.

"The findings suggest that once you have experienced trauma early in life, it changes how you respond to the environment and how your biology is hardwired. Apparently, children with this background are more likely to have amygdala-based overreactions.

"We need to recognize this, identify these children, and use this as a starting place for teaching them alternative adaptive strategies. They may need active intervention early on to better tolerate the stressors that life will throw at them," said Dr. Bradley.

Dr. Tottenham and Dr. Bradley have disclosed no relevant financial relationships.

Anxiety Disorders Association of America (ADAA) 31st Annual Conference. Presented March 26, 2011.

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