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J Child Adolesc Psychopharmacol. 2008 Apr;18(2):132-9. doi: 10.1089/cap.2007.0088.

Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium.

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  • 1College of Pharmacy, University of Georgia, Medical College of Georgia, Augusta, Georgia 30912-2450, USA.



This proton magnetic resonance spectroscopy (1H MRS) study identified the in vivo effects of lithium on N-acetyl-aspartate (NAA) concentrations in adolescent bipolar depression.


Twenty eight adolescents with bipolar I disorder in a depressive episode received open-label lithium 30 mg/kg, adjusted to achieve serum levels of 1.0-1.2 mEq/L. Medial ventral and ventral lateral prefrontal NAA concentrations were measured at baseline, day 7, and day 42 of treatment. Temporal changes in NAA concentrations were analyzed and effect sizes (Cohen's d) were calculated.


Medial ventral prefrontal NAA concentrations decreased over time (p = 0.03), with day-42 concentrations significantly lower than baseline concentrations (p = 0.01, d = 0.7). No significant time effects on NAA concentrations were observed in the left (p = 0.2) or right ventral lateral (p = 0.3) prefrontal cortices.


In contrast with prior studies of bipolar adults, this study observes that ventral prefrontal NAA concentrations do not significantly increase from baseline following lithium treatment in adolescent bipolar depression. The results should be viewed in the context of the study's limitations, including the lack of a matched healthy control group. Additional longitudinal magnetic resonance imaging studies are warranted to understand better the role of NAA in the pathophysiology of bipolar disorder and neurochemical mechanisms by which lithium stabilizes mood.

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