Pathological gambling: a comprehensive review of biobehavioral findings

Abstract

In this review, findings of biobehavioral research into pathological gambling (PG) are discussed, focusing on neuropsychological, psychophysiological, neuroimaging, neurochemical and genetic studies. Neuropsychological studies indicate deficiencies in certain executive functions. Psychophysiological studies indicate that arousal in PG is of importance when reward is present. Neuroimaging studies point to abnormalities in brain functioning. Recent research into the neurochemistry of PG indicates that abnormalities exist in different neurotransmitter systems. Finally, genetic studies indicate the existence of abnormal dopamine receptor genes in PG. Methodological and theoretical factors that may explain discrepancies between studies include differences in screening and assessment, heterogeneity of gambling problems and different underlying cognitive or motivational mechanisms. Results from the PG studies fit in with recent theoretical models of addiction and PG, which stress the involvement of brain reward pathways, neurotransmitter abnormalities, the frontal cortex and the psychophysiological stress system. A framework for future studies is suggested, indicating the need for studies that integrate knowledge from different research areas, and that employ stricter diagnostic screening methods and inclusion of clinical control groups.

Introduction

Pathological gambling (PG) is characterized by persistent, non-adaptive gambling and the disorder is classified as an impulse control disorder in the Diagnostic and Statistical Manual of Mental Disorders IV [1]. Prevalence estimations of PG vary, but a recent review estimates the lifetime prevalence of PG at 1.6% in the United States and Canada [2]. PG is a serious public health problem. With growing availability of gambling opportunities, prevalence of PG rises [3]. PG poses psychosocial problems to the person involved, often causes financial problems and can lead to social disruption [4], [5], [6], [7]. Furthermore, PG is associated with a higher rate of suicidal ideation and suicide attempts [5], [8], [9]. Knowledge about the etiology of this disorder is limited, although recent studies suggest genetic vulnerability, and involvement of abnormal neurotransmitter availability (for a review, see Ref. [10]).

Although PG is classified as an impulse control disorder in the DSM-IV [APA,1], and PG is studied as an impulse control and/or obsessive compulsive disorder [11], [12], PG is often regarded as a behavioral or non-chemical addiction [4], [13], [14]. Psychologically, the commonality between behavioral and substance dependencies is the enduring engagement in uncontrolled self-destructive behavior, despite its negative consequences. The DSM-IV encompasses diagnostic criteria for PG, such as the failure to resist the urge to gamble, feelings of restlessness when not able to gamble, and gambling more and more to produce the same excitement. These criteria closely resemble diagnostic criteria of substance dependence, such as tolerance and withdrawal. Studies indicate that tolerance [15] and craving [16] are present in PG, further underlining the resemblance of PG and substance dependencies. The high comorbidity between alcohol or drug dependence and PG, in combination with genetic studies evidencing common genetic factors in PG and alcohol dependence, point to common etiological factors [17], [18].

Addictive behaviors in general and PG in particular may also be viewed as disorders characterized by a lack of self-regulation. In PG there is a lack of self-regulation when gambling continues despite its negative consequences. A lack of self-regulation is displayed when an addicted person is not able to inhibit his urge for the desired drug or behavior, and to shift his behavior from the addictive reinforcement to a less self-destructive reinforcer. Thus, deficits in self-regulation could complicate the process of change needed when trying to quit using drugs or gambling. The deficits displayed behaviorally in PG, could have a basis in structural and functional brain abnormalities involved in self-regulation. In various addictions, abnormalities have been found in the prefrontal cortex and subcortico-cortical networks projecting to the frontal cortex [19], [20], [21], areas which are important in executive functions (EFs, for a review, see Ref. [22]). EFs are the supervisory cognitive functions that guide behavior. Key EFs include planning, response modulation and inhibition, which all play an important role in self-regulation [23]. Abnormalities in EFs could be regarded as a consequence of repeated drug use on brain structures. However, developmental studies also show that mild dysfunctions in EFs (i.e. impulsiveness, risk-taking and disinhibition) mediate the enhanced risk for later development of addictions in children with a familial risk for developing alcoholism [24], [25]. The resemblance in deficits in self-regulation in PG and substance dependencies, raises the question whether in PG, like in addictions, deficits are present in neuropsychological functions which tap self-regulation. There exists some research on EFs in PG, and therefore in this review findings of neuropsychological studies in PG are reported.

Current neurobiological research indicates abnormal neurotransmitter regulation in the ‘reward pathways’ of the brain in addicted persons [22]. An abnormal functioning of mesolimbic structures could result in an abnormal sensitivity for reward or loss, or to a combination of these. Dysregulation of neurotransmitters such as dopamine, plays a role in withdrawal and craving in addiction [26] and dopamine is one of the main neurotransmitters of mesolimbic brain structures. In PG there is also evidence for abnormal levels of dopamine further evidencing a link between PG and other addictions [27]. The limbic structures involved in sensitivity for reward and loss also play an important role in regulating arousal. Thus, abnormalities in these mesolimbic brain structures could also result in an abnormal arousal regulation in PG, resulting in longer play, either through higher arousal, leading to disinhibition, through overall lower arousal levels which encourage thrill seeking behavior to heighten arousal, or through the absence of higher arousal when losses are experienced [10], [28], [29], [30]. Given the abnormalities found in addiction in brain structures and functions and the resemblance between PG and addiction, in this review, an overview of findings in PG is given of studies involving psychophysiology during reward and/or loss, neuroimaging, neurochemistry and genetics, so as to establish an overview of biobehavioral findings in PG research.

The resemblance of PG and substance use disorders, the behavioral resemblance of dysfunctional self-regulation in PG and substance dependence, and the accumulating evidence of neurobiological abnormalities in addiction call for a review of biobehavioral findings in PG, and for the integration of findings in different research fields. General reviews exist on PG [31], [32], [33], [34], on the neurobiology of PG [35], the psychopharmacology of PG [36] and the genetics of PG [10], but to our knowledge, no review exists incorporating the above-mentioned research fields. Therefore, in this comprehensive review of the existing literature, studies regarding the biobehavioral functioning in PG are discussed, covering (1) neuropsychological studies, (2) psychophysiological studies, (3) neuroimaging, (4) neurotransmitter and (5) genetic studies. In the discussion sections, strengths and limitations of the studies are reviewed and in the general discussion a theoretical framework for future biobehavioral research into PG is presented.