Dopaminergic mechanisms underlying normal variation in trait anxiety: supplemental

Trait anxiety has been associated with altered activity within
corticolimbic pathways connecting the amygdala and rostral anterior
cingulate cortex (rACC), which receive rich dopaminergic input. Though the
popular culture uses the term “chemical imbalance” to describe the
pathophysiology of psychiatric conditions such as anxiety disorders, we
know little about how individual differences in human dopamine
neurochemistry are related to variation in anxiety and activity within
corticolimbic circuits. We addressed this issue by examining
inter-individual variability in dopamine release at rest using
[11C]raclopride PET, functional connectivity between amygdala and rACC
using resting-state fMRI, and trait anxiety measures in healthy adult male
and female humans. To measure endogenous dopamine release, we collected
two [11C]raclopride PET scans per participant. We contrasted baseline
[11C]raclopride D2/3 receptor binding and D2/3 binding following oral
methylphenidate administration. Methylphenidate blocks the dopamine
transporter, which increases extracellular dopamine and leads to reduced
[11C]raclopride D2/3 receptor binding via competitive displacement. We
found a negative relationship between dopamine release and trait anxiety
such that individuals with higher dopamine release in the amygdala and
rACC self-reported lower trait anxiety. Lower trait anxiety was also
associated with reduced rACC-amygdala functional connectivity at baseline.
Further, functional connectivity showed a modest negative relationship
with dopamine release such that reduced rACC-amygdala functional
connectivity was accompanied by higher levels of dopamine release in these
regions. Together, these findings contribute to hypodopaminergic models of
anxiety and support the utility of combining fMRI and PET measures of
neurochemical function to advance our understanding of basic affective
processes in humans.