Deformations of amygdala morphology in familial pediatric bipolar disorder

Objective: Smaller amygdalar volumes have been consistently observed in pediatric bipolar disorder subjects compared to healthy control subjects. Whether smaller amygdalar volume is a consequence or antecedent of the first episode of mania is not known. Additionally, smaller volume has not been localized to specific amygdala subregions.

Methods: We compared surface contour maps of the amygdala between 22 youths at high risk for bipolar disorder, 26 youths meeting full diagnostic criteria for pediatric familial bipolar disorder, and 24 healthy control subjects matched for age, gender, and intelligence quotient. Amygdalae were manually delineated on three-dimensional spoiled gradient echo images by a blinded rater using established tracing protocols. Statistical surface mesh modeling algorithms supported by permutation statistics were used to identify regional surface differences between the groups.

Results: When compared to high-risk subjects and controls, youth with bipolar disorder showed surface deformations in specific amygdalar subregions, suggesting smaller volume of the basolateral nuclei. The high-risk subjects did not differ from controls in any subregion.

Conclusions: These findings support previous reports of smaller amygdala volume in pediatric bipolar disorder and map the location of abnormality to specific amygdala subregions. These subregions have been associated with fear conditioning and emotion-enhanced memory. The absence of amygdala size abnormalities in youth at high risk for bipolar disorder suggests that reductions might occur after the onset of mania.