Progression of amygdala volumetric abnormalities in adolescents after their first manic episode

Abstract

Objective: Although previous neuroimaging studies suggest that adolescents with bipolar disorder exhibit smaller amygdala volumes compared with healthy adolescents, whether these abnormalities are present at illness onset or instead develop over time remains unclear. The aim of this study was to conduct a prospective longitudinal investigation comparing amygdala neurodevelopment among adolescents after their first manic episode, adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy adolescents.

Method: A total of 30 adolescents hospitalized for their first manic/mixed episode associated with bipolar disorder, 29 adolescents with ADHD, and 24 demographically matched healthy teens underwent magnetic resonance imaging scanning at index assessment and approximately 12 months later. Adolescents with bipolar disorder were prospectively evaluated using diagnostic interviews and with symptom rating scales.

Results: Mixed models examining the group × time effect for both left (p = .005) and right (p = .002) amygdala volumes were statistically significant. Change in left (p = .01) and right (p = .0008) amygdala volumes from baseline to 12 months were significantly different among groups. Specifically, left amygdala volumes increased over time in healthy adolescents (p = .008) and adolescents with ADHD (p = .0009), but not in adolescents with bipolar disorder (p = .3). Right amygdala volume increased over time in adolescents with ADHD (p < .001), but not in healthy adolescents nor in adolescents with bipolar disorder (p = .1 and p = .3, respectively). In adolescents with bipolar disorder, baseline total amygdala volume was significantly greater in those who subsequently achieved symptomatic recovery as compared with those who did not achieve recovery (p = .02).

Conclusions: Adolescents with mania do not exhibit normal increases in amygdala volume that occur during healthy adolescent neurodevelopment.

Figure 1

Adjusted volumetric changes from baseline to 12 months in adolescents with bipolar disorder (n=30), adolescents with attention deficit hyperactivity disorder (ADHD; n=29), and healthy (n=24) adolescents in A. left amygdala (mixed model group*time effect, p=0.005) and B. right amygdala (mixed model group*time effect, p=0.002). * At 12 months, adolescents with bipolar disorder exhibit statistically significantly differences in A. left amygdala volume compared with adolescents with attention deficit hyperactivity disorder (ADHD; p=0.0002) and healthy adolescents (p=0.0002) and B. in right amygdala volume compared with adolescents with attention deficit hyperactivity disorder (ADHD; p=0.0002) and healthy adolescents (p=0.003) ** Volume change from baseline to 12 months is significant for: A. left amygdala in healthy adolescents (p=0.008) and adolescents with attention deficit hyperactivity disorder (ADHD; p=0.0009) and B. right amygdala in adolescents with attention deficit hyperactivity disorder (ADHD; p<0.0001).

Figure 2

Left and right amygdala volume and symptom severity (YMRS) at baseline for adolescents with bipolar disorder (n=30) Note: Baseline amygdala volume is significantly correlated with baseline YMRS scores. A. Left amygdala (p=0.02, R=0.43). B. Right amygdala (p=0.02, R=0.41).

Figure 3

Baseline total amygdala volume for adolescents with bipolar disorder who did (n=9) and did not (n=11) achieve symptomatic recovery. Note: Baseline total amygdala volume was significantly greater in those who subsequently achieved symptomatic recovery as compared to those who did not experience symptomatic recovery during the initial year following their first manic episode (d=1.34, p=0.02).