Circuitry elements in the effect of the Val/Val genotype on dopamine levels.

<p>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 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142862#pone.0142862.ref029" target="_blank">29</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142862#pone.0142862.ref030" target="_blank">30</a>]. In the striatum, the direct influence of COMT is weak because the dopamine level is predominantly regulated by dopamine reuptake through presynaptic transporters [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142862#pone.0142862.ref031" target="_blank">31</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142862#pone.0142862.ref032" target="_blank">32</a>]. 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.</p

Demographic Characteristics of Participants.

<p>Demographic Characteristics of Participants.</p

Clusters of significantly decreased gray matter volume in Val/Val individuals compared with that in Val/Met individuals.

<p>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.</p

Results of Voxel-based morphometry analysis.

<p>Val = Valine; Met = Methionine; MDD = Major depression disorders; HS = healthy subjects; COMT = Catechol-O-methyltransferase, FDR = false discovery rate, MNI = Montreal Neurological Institute</p><p>Results of Voxel-based morphometry analysis.</p

Demographic and Clinical Characteristics of Participants.

<p>Demographic and Clinical Characteristics of Participants.</p

Results of the analysis of the diagnosis effects (HS versus MDD).

<p>The images show statistical parametric maps {SPM (t)}. The volume of the superior temporal cortex is significantly smaller in the MDD patients than in the HS (FWE corrected p = 0.02).</p

Results of VBM analysis.

<p>Results of VBM analysis.</p

Box plots of the analysis of the G1287A genotype—diagnosis interaction.

<p>These box plots show the medians, quartiles and ranges of the GM volumes of the cluster in left dorsolateral prefrontal cortex. The dot at the "MDD with A/- genotype" represent an outlier.</p

Background of smokers and non-smokers.

<p>Abbreviation. AUDIT: Alcohol Use Disorders Identification Test; TDS: Tobacco Dependence Screener Scale; FTND: Fagerström Test for Nicotine Dependence; CO; carbon monoxide.</p><p>*Detailed information about the smoking-related clinical variables and the AUDIT scores of three subjects (N = 16) were not available. The mean AUDIT scores of the smokers (N = 16) was significantly higher than that of the nonsmokers (N = 18; smokers: 9.1±6.3; nonsmokers: 4.9±4.4; p = 0.022).</p

The correlation between FA levels throughout the whole corpus callosum and the amount of tobacco use (N = 16).

<p>There was a significant negative correlation between FA levels throughout the whole corpus callosum and the amount of tobacco use covariant age (cigarettes/day; R = − 0.580, <i>p</i> = 0.023). The number of spots was decreased from 16 to 13 because three spots represented the same data (three represented the FA level = 0.52 and N = 15, and two represented the FA level = 0.55 and N = 20; these spots are shown in gray spots).</p