Fig 1.
Hypothetical inverted U-shaped relationship between prefrontal cortex (PFC) brain function and dopamine levels.
Intermediate COMT activity and dopamine levels present in Val/Met individuals are thought to be optimal for PFC-mediated brain function.
Table 1.
Demographic Characteristics of Participants.
Fig 2.
Clusters of significantly decreased gray matter volume in Val/Val individuals compared with that in Val/Met individuals.
The SPM {t} is displayed onto the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) template of gray matter. The volumes of the bilateral caudate and posterior cingulate cortex (PCC) were significantly smaller in Val/Val individuals than in Val/Met individuals (yellow areas). A-C: The sagittal, axial, and coronal images of the PCC. D: The sagittal image of the right caudate. E-F: The axial and corneal images of the bilateral caudate. G: The sagittal image of the left caudate. H: The color bar indicates the T-value.
Table 2.
Results of Voxel-based morphometry analysis.
Fig 3.
Circuitry elements in the effect of the Val/Val genotype on dopamine levels.
Relative to the Val/Met genotype, the COMT enzyme from the Val/Val genotype leads to reduced dopamine levels in the cortex, including the PFC and PCC. Although projections from the PFC to the midbrain directly contact dopaminergic cell groups in the ventral tegmental area that project back to the PFC to generate low dopamine levels, they indirectly elevate the dopamine levels via dopaminergic cell groups in the substantia nigra that project to the striatum [29, 30]. In the striatum, the direct influence of COMT is weak because the dopamine level is predominantly regulated by dopamine reuptake through presynaptic transporters [31, 32]. Therefore, Val/Val individuals have lower dopamine levels in the PCC and higher dopamine levels in the caudate than those in Val/Met individuals. DA = dopamine, PFC = prefrontal cortex, PCC = posterior cingulate cortex, VTA = ventral tegmental area, and SN = substantia nigra.