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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 x time effect for both left (p = 0.005) and right (p = 0.002) amygdala volumes were statistically significant. Change in left (p = 0.01) and right (p = 0.0008) 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 = 0.0009), but not in adolescents with bipolar disorder (p = 0.3). Right amygdala volume increased over time in adolescents with ADHD (p less than 0.001), but not in healthy adolescents nor in adolescents with bipolar disorder (p = 0.1 and p = 0.3, 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 = 0.02). Conclusions: Adolescents with mania do not exhibit normal increases in amygdala volume that occur during healthy adolescent neurodevelopment. (Contains 2 tables and 3 figures.)

Objective: Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among adolescents with bipolar disorder (bipolar group; n = 14), adolescents with a cannabis use disorder (cannabis use group; n = 13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group; n = 25), and healthy adolescents (healthy controls; n = 15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups., Methods: N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using proton magnetic resonance spectroscopy., Results: Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p = .0002 and p = .0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations., Conclusions: Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder.