Non-Substance-Related Disorders: Gambling disorder and internet addiction

Behavioral addictions are highly prevalent and have a major individual and societal impact. Moreover, given the availability and increase of potentially addictive activities in our societal development (e.g. internet, gaming, online pornography) an increase in these types of behavioral disorders is very likely. Gambling Disorders are best studied among the non-chemical addictions. However, effective treatment interventions need to be further developed, in particular for Internet Addiction. Most of the available evidence supports behavioral interventions as first line treatment. Specifically for Gambling Disorder, pharmacotherapy can be an useful augmentation.. Psychiatric comorbidities are frequent in patients with behavioral addictions and negatively affect the course of non-substance-related disorders. Concurrent treatment of these comorbid disorders is advised, although there is a clear need of conducting studies evaluating the effectiveness of integrated treatment approaches.

The role of learning-related dopamine signals in addiction vulnerability

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction.

Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior

BACKGROUND There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. METHODS We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. RESULTS Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. CONCLUSIONS These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.

Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers.

BACKGROUND Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. METHODS Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. RESULTS Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. CONCLUSIONS This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies.

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.