Anhedonia in Parkinson's disease patients with and without pathological gambling: A case-control study

Abstract

Anhedonia is present in Parkinson's Disease (PD) as well as in addictive behaviors. Pathological Gambling (PG) and other Impulse Control Disorders (ICDs) have emerged as iatrogenic complications associated with dopamine replacement therapy. We studied 154 PD patients, divided into three groups: 11 with PG, 23 with other ICDs (compulsive buying, hypersexuality, binge eating), 120 without ICDs. All patients underwent a thorough clinical, neuropsychological and psychiatric evaluation. The PG-group, compared to the ICDs-group and PD-controls, reported a significantly higher incidence of anhedonia (45% vs. 9% vs. 14% respectively), higher Snaith–Hamilton Pleasure Scale (SHAPS) scores (2.0±1.3 vs. 1.0±1.1 vs. 1.0±1.2), higher levels of impulsivity traits as measured by the Barratt Impulsiveness Scale (70.0±10.6 vs. 64.8±11 vs. 60.9±9.3) and more severe frontal dysfunctions (Frontal Assessment Battery, FAB: 12.4±4.9 vs. 15.5±1.6 vs. 14.4±3). A model for PG (incorporating anhedonia, impulsivity levels and frontal impairment) is discussed in the context of the pathophysiology of addictive behaviors. The impairment of hedonic capacity, possibly resulting from an underlying neuropsychological dysfunction, might facilitate loss of control over reward-related behavior, thus favoring the shift towards predominantly habit-based compulsive behaviors.

Introduction

Anhedonia refers to the reduced ability to experience pleasure. Operationally, it may be defined as diminished interest or pleasure in response to stimuli usually perceived as rewarding (American Psychiatric Association, 2000). It may be considered both as an enduring personality trait predisposing to the development of schizophrenia and depression, as well as a core symptom of these conditions (Pelizza and Ferrari, 2009). Other studies suggest that anhedonia may be involved in the transition from recreational use to excessive drug intake in patients with substance use disorders (Ahmed and Koob, 1998). From a neurobiological perspective, a central dopaminergic dysfunction has been widely proposed as a neurobiological correlate of anhedonia. The dopaminergic mesolimbic and mesocortical circuits, which comprise the Ventral Tegmental Area (VTA), the ventral striatum, and part of the prefrontal cortex, are activated by rewarding events, behaviors, objects, and physical or emotional states, with the function of ascribing them a positive value. In addition to dopamine, other neurotransmitters mediate the hedonic experience, namely serotonin and endogenous opioids (Kranz et al., 2010).

Compared to controls, anhedonia levels were significantly higher in patients with Parkinson's Disease (PD), with a prevalence rate of 40% (Isella et al., 2003). Indeed, degenerative changes of the dopaminergic system are not limited to structures regulating motor function but may also involve limbic areas (Braak and Braak, 2000). Several studies (systematically reviewed by Assogna et al., 2011) found anhedonia to be strictly related to depression, apathy and lack of motivation, whereas the relationship between anhedonia and motor symptoms is still unclear.

In the last decade, Pathological Gambling (PG) and other Impulse Control Disorders (ICDs) have emerged as a iatrogenic complication associated with Dopaminergic Replacement Treatment (DRT) of PD (Vilas et al., 2012, Raja and Bentivoglio, 2012). The lifetime prevalence of PG in PD patients ranges from 2.2% to 7% (Djamshidian et al., 2011, Santangelo et al., 2013a), and is much higher than in the general population (0.42–2.5%). In recent large studies, ICDs were strongly associated with the use of dopamine agonists in general, without associations with specific molecules (Weintraub et al., 2006, Weintraub et al., 2010, Voon et al., 2011). The occurrence of ICDs in only a subset of PD patients suggests that intrinsic features play a role in their pathogenesis (Raja and Bentivoglio, 2012). Some conditions, such as young age, novelty-seeking traits and alcohol dependence, have been recognized as predisposing factors for the development of ICDs (Pontone et al., 2006, Voon et al., 2007, Voon et al., 2011). Recent studies found an association between the presence of ICDs and psychiatric symptoms (including depressive, obsessive and anxiety symptoms; Voon et al., 2011). Inconsistent results have been reported on cognitive impairments (Santangelo et al., 2009b, Siri et al., 2010, Vitale et al., 2011, Bentivoglio et al., 2013), mainly related to frontal lobe dysfunction (ventral frontostriatal networks; Santangelo et al., 2009b, Bentivoglio et al., 2013). On this basis, it has been suggested that PG and other ICDs are behavioral symptoms that might arise from a top-down dysregulation of behavior, and that differences among subtypes of ICDs may reflect differential involvement of the neural substrates devoted to process intrinsic (i.e., sex and eating) or learned rewards (i.e., money; Vitale et al., 2011, Santangelo et al., 2013b).

ICDs in the general population have epidemiological and phenomenological overlaps with substance addiction, leading to their classification as behavioral addictions (Potenza, 2008). Given that in substance use disorder patients anhedonia is part of the abstinence symptomatology (Martinotti et al., 2008b) and has been found to be an important factor in precipitating relapse (Hatzigiakoumis et al., 2011, Koob and Le Moal, 2001), the aim of the present study was to test the hypothesis that some psychiatric traits, and particularly anhedonic features, might be associated with the development of PG and other ICDs in PD patients.