Abstract
Impulse control disorders (ICDs), including disordered gambling, can occur in a significant number of patients with Parkinson’s disease (PD) receiving dopaminergic therapy. The neurobiology underlying susceptibility to such problems is unclear, but risk likely results from an interaction between dopaminergic medication and a pre-existing trait vulnerability. Impulse control and addictive disorders form part of a broader psychopathological spectrum of disorders, which share a common underlying genetic vulnerability, referred to as externalizing. The broad externalizing risk factor is a continuously varying trait reflecting vulnerability to various impulse control problems, manifested at the overt level by disinhibitory symptoms and at the personality level by antecedent traits such as impulsivity and novelty/sensation seeking. Trait “disinhibition” is thus a core endophenotype of ICDs, and a key target for neurobiological investigation. The ventral striatal dopamine system has been hypothesized to underlie individual variation in behavioral disinhibition. Here, we examined whether individual differences in ventral striatal dopamine synthesis capacity predicted individual variation in disinhibitory temperament traits in individuals with PD. Eighteen early-stage male PD patients underwent 6-[18F]Fluoro-l-DOPA (FDOPA) positron emission tomography scanning to measure striatal dopamine synthesis capacity, and completed a measure of disinhibited personality. Consistent with our predictions, we found that levels of ventral, but not dorsal, striatal dopamine synthesis capacity predicted disinhibited personality, particularly a propensity for financial extravagance. Our results are consistent with recent preclinical models of vulnerability to behavioral disinhibition and addiction proneness, and provide novel insights into the neurobiology of potential vulnerability to impulse control problems in PD and other disorders.
Highlights
Several addictive and impulse control disorders (ICDs) have been associated with Parkinson’s disease (PD) and its treatment with dopaminergic medication, including disordered gambling (Gallagher et al, 2007), substance dependence (Bienfait et al, 2010), and the addiction-like excessive use of dopaminergic medications, or DA dysregulation syndrome (Lawrence et al, 2003)
In line with our a priori hypothesis, we found a significant correlation between NS3 (Extravagance) scores and left ventral striatum (VS) FDOPA K I values [r (16) = 0.61, p = 0.008, 95% CI 0.20 – 0.83; Figure 2]
Consistent with our hypothesis, we found that variation in trait disinhibition, a continuously varying endophenotype for EXT or impulse-control psychopathology, was associated with levels of DA synthesis capacity in the VS
Summary
Several addictive and impulse control disorders (ICDs) have been associated with Parkinson’s disease (PD) and its treatment with dopaminergic medication, including disordered gambling (Gallagher et al, 2007), substance dependence (Bienfait et al, 2010), and the addiction-like excessive use of dopaminergic medications, or DA dysregulation syndrome (Lawrence et al, 2003). The development of ICDs in PD likely results from an interaction between dopaminergic medication and an underlying vulnerability, rather than from PD itself, since: (a) only a (substantial) minority of medicated PD patients develop ICDs (Weintraub et al, 2010); (b) ICDs are no more frequent in patients with de novo PD than in the general population (Weintraub et al, 2013); (c) ICDs can develop in non-PD individuals treated with dopaminergic medication (O’Sullivan et al, 2010; Voon et al, 2011a); and (d) a family history of gambling problems is a risk factor for the development of dopaminergic medication-linked ICDs (Weintraub et al, 2010; Voon et al, 2011a) This precursive ICD vulnerability likely reflects variation in preexisting temperament/personality (Dagher and Robbins, 2009), in particular, variation in the broad temperament dimension of trait disinhibition (vs constraint), encompassing impulsivity, novelty/sensation seeking, non-planning, low self-control, and related constructs (Markon et al, 2005). I.e., putatively distinct disorders are better understood as variants within a broader www.frontiersin.org
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