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Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

      Abstract

      Background

      Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences.

      Methods

      We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty.

      Results

      Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala.

      Conclusions

      Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms.

      Keywords

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      • Sex Differences and Personalized Psychiatric Care
        Biological PsychiatryVol. 80Issue 10
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          A single mother who has struggled in the past with anxiety and depression has healthy 12-year-old twins and asks when her son and daughter might develop similar symptoms. Specifically, she’s concerned that her daughter has recently been more worried about school. You embark on the familiar conversation that both children are at familial risk. The patient, however, presses on that she wants to know what she might expect with each child and, specifically, whether her daughter might be at increased risk compared to her son.
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