Dataset Information

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis.

ABSTRACT: Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARI-induced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of both GD and ARI's clinical response to a genetic polymorphism on the D2 receptor (DRD2/ANKK1 Taq1A; rs1800497), the hypothesis regarding the origin of this phenomenon could be found in the altered sensitization of dopamine's receptors that certain individuals carry genetically. The identification of a possible genetic susceptibility (detectable by genetic tests) could provide clinicians with an explanation for the ARI-induced GD and the possibility of using genetic screening tools for those cases of suspected predisposition; this would allow the clinician to prescribe ARI with less apprehension. The confirmation of this hypothesis through future pharmacogenetic studies may be useful for clinicians to have a correct understanding of the phenomenon.

SUBMITTER: Miuli A

PROVIDER: S-EPMC7174678 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis.

Miuli Andrea A Pettorruso Mauro M Romanelli Ester E Stigliano Gianfranco G Di Giuda Daniela D De-Giorgio Fabio F Martinotti Giovanni G di Giannantonio Massimo M

Frontiers in psychiatry 20200415

Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARI-induced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of b ...[more]

PMID: 32351415

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Project description:Gambling Disorder (GD) has recently been reclassified from an impulse-control disorder to a behavioural addiction and, as in other addictive disorders, the dopaminergic reward system is involved. According to neuroimaging studies, alterations within the striatal dopaminergic signalling can occur in GD. However, the findings to date are controversial and there has been no agreement yet on how the reward system is affected on a molecular basis. Within the last 20 years, there has been growing evidence for a higher risk to develop GD in response to certain dopaminergic medication. Especially the dopamine agonists pramipexole and ropinirole, and the dopamine modulator aripiprazole seem to increase the likelihood for GD. The goal of this study was to examine the association between a prescription for either of the three pharmaceuticals and a GD diagnosis in a large cross-sectional study of the Swedish population. Compared to patients with any other dopaminergic drug prescription (38.7% with GD), the diagnosis was more common in patients with a dopamine agonist prescription (69.8% with GD), resulting in an odds ratio of 3.2. A similar association was found between aripiprazole prescriptions and GD diagnoses, which were analysed within the subgroup of all patients with schizophrenia or a schizotypal, delusional, or another non-mood psychotic disorder. An aripiprazole prescription increased the likelihood of GD (88.8%) in comparison to patients without an aripiprazole prescription (71.2%) with an odds ratio of 3.4. This study contributes to the increasingly reliable evidence for an association between several dopaminergic drugs and a higher risk for developing GD. Therefore, one future research goal should be a better understanding of the neurobiology in GD to be able to design more selective dopaminergic medication with less severe side effects. Additionally, this knowledge could enable the development of pharmacotherapy in GD and other addictive disorders.

Project description:Gambling Disorder is a prevalent psychiatric condition often linked to dysfunction of cognitive domains regulating impulsive behavior. Despite the centrality of impulsivity to neurobiological models of Gambling Disorder, a comprehensive meta-analysis of all impulsive cognitive domains has yet to be conducted. It is also not clear whether cognitive deficits in Gambling Disorder extend to those with problem (at-risk) gambling. A systematic review was undertaken of case-control studies examining the following cognitive domains in Gambling Disorder or in at-risk (problem) gambling: attentional inhibition, motor inhibition, discounting, decision-making, and reflection impulsivity. Case-control differences in cognition were identified using meta-analysis (random-effects modeling). Moderation analysis explored potential influences of age, gender, presence/absence of comorbidities in cases, geographical region, and study quality on cognitive performance. Gambling Disorder was associated with significant impairments in motor (g = 0.39-0.48) and attentional (g = 0.55) inhibition, discounting (g = 0.66), and decision-making (g = 0.63) tasks. For problem gambling, only decision-making had sufficient data for meta-analysis, yielding significant impairment versus controls (g = 0.66); however, study quality was relatively low. Insufficient data were available for meta-analysis of reflection impulsivity. There was evidence for significant publication bias only for the discounting domain, after an outlier study was excluded. Study quality overall was reasonable (mean score 71.9% of maximum), but most studies (~85%) did not screen for comorbid impulse control and related disorders. This meta-analysis indicates heightened impulsivity across a range of cognitive domains in Gambling Disorder. Decision-making impulsivity may extend to problem (at-risk) gambling, but further studies are needed to confirm such candidate cognitive vulnerability markers.

Dataset Information

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis.

Publications

Does DRD2 Taq1A Mediate Aripiprazole-Induced Gambling Disorder? A Pharmacogenetic Hypothesis.

Similar Datasets

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