Abstract
Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. All participants had one magnetic resonance imaging (MRI) and two [11C]raclopride positron emission tomography scans. Associations between frontal cortical thickness and the magnitude of d-amphetamine-induced [11C]raclopride binding changes were observed that were divergent in the two groups. In the healthy controls, a thicker cortex was associated with less dopamine release; in the ADHD participants the converse was seen. The same divergence was seen for baseline D2/3 receptor availability. In healthy volunteers, lower D2/3 receptor availability was associated with a thicker cortex, while in the ADHD group lower baseline D2/3 receptor availability was associated with a thinner cortex. Individual differences in cortical thickness in these regions correlated with ADHD symptom severity. Together, these findings add to the evidence of associations between dopamine transmission and cortical morphology, and suggest that these relationships are altered in treatment-naïve adults with ADHD.
Highlights
Attention deficit hyperactivity disorder (ADHD) is thought to arise in part from alterations in catecholamine signaling (Castellanos et al, 1994; Spencer et al, 2005, 2013; Volkow et al, 2009; Cherkasova et al, 2014) and structural abnormalities in multiple cortico-striatal circuits (Nakao et al, 2011; Castellanos and Proal, 2012)
No participant was clinically depressed, the attention deficit/hyperactivity disorder (ADHD) Beck Depression Inventory (BDI) scores at intake were higher than those of Controls. Because of this group difference and a significant correlation between BDI and BPND in ADHD participants only (r = −0.68 p = 0.007), BDI was considered as a covariate, but it was not used in the final models since it did not improve the fit
In ADHD subjects, there were significant BPND decreases in all three region of interest (ROI) [AST: t(14) = 2.15, p = 0.05; SMST: t(14) = 3.24, p = 0.006; LST: t(14) = 2.36, p = 0.03), and these effects were significantly greater than those seen in the controls within both the AST and SMST [Group × ROI interaction: F(1.36, 39.70) = 4.07; p = 0.04; AST: F(1, 30) = 4.24, p = 0.05; SMST: F(1, 30) = 4.73, p = 0.04]
Summary
Attention deficit hyperactivity disorder (ADHD) is thought to arise in part from alterations in catecholamine signaling (Castellanos et al, 1994; Spencer et al, 2005, 2013; Volkow et al, 2009; Cherkasova et al, 2014) and structural abnormalities in multiple cortico-striatal circuits (Nakao et al, 2011; Castellanos and Proal, 2012) DA depletion in adult animals likewise results in dystrophic changes to prefrontal dendrites (Wang and Deutch, 2008), and D1 receptor antagonism reduces prefrontal synaptic density (Imai et al, 2004) Some of these effects might begin early in development, and there have been reports that neonatal DA depletion causes reductions in cortical thickness (CT) (Kalsbeek et al, 1987; Alvarez et al, 2002). Recent studies suggest that, in healthy volunteers, gray matter density and volume are related to D2 receptor availability (measured with [18F]fallypride) in the midbrain, striatum, thalamus, amygdala, and diverse cortical areas (Woodward et al, 2009), while striatal DA release is related to CT (Casey et al, 2013; Jaworska et al, 2017) and cortico-striatal anatomical connectivity (Tziortzi et al, 2014)
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