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Gambling Disorder (GD) is an impactful behavioural addiction for which there appear to be underpinning genetic contributors. Twin studies show significant GD heritability results and intergenerational transmission show high rates of transmission. Recent developments in polygenic and multifactorial risk prediction modelling provide promising opportunities to enable early identification and intervention for at risk individuals. People with GD often have significant delays in diagnosis and subsequent help-seeking that can compromise their recovery. In this paper we advocate for more research into the utility of polygenic and multifactorial risk modelling in GD research and treatment programs and rigorous evaluation of its costs and benefits.

Gambling Disorder (GD) has a complex etiology that involves biological and environmental aspects. From a genetic perspective, neurotrophic factors (NTFs) polymorphisms have been associated with the risk of developing GD. The aim of this study was to assess the underlying mechanisms implicated in GD severity by considering the direct and mediational relationship between different variables including genetic, psychological, socio-demographic, and clinical factors. To do so, we used genetic variants that were significantly associated with an increased risk for GD and evaluated its relationship with GD severity through pathway analysis. We found that the interaction between these genetic variants and other different biopsychological features predicted a higher severity of GD. On the one hand, the presence of haplotype block 2, interrelated with haplotype block 3, was linked to a more dysfunctional personality profile and a worse psychopathological state, which, in turn, had a direct link with GD severity. On the other hand, having rs3763614 predicted higher general psychopathology and therefore, higher GD severity. The current study described the presence of complex interactions between biopsychosocial variables previously associated with the etiopathogenesis and severity of GD, while also supporting the involvement of genetic variants from the NTF family.

Background and Aims: Proper measurement of expected risk is important for making rational decisions, and maladaptive decision making may underlie various psychiatric disorders. However, differentially expressed genetic profiling involved in this process is still largely unknown. A rodent version of the gambling task (rGT) has been developed to measure decision-making by adopting the same principle of Iowa Gambling Task in humans. In the present study, we examined using next-generation sequencing (NGS) technique whether there are differences in gene expression profiles in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc) when rats make different choices toward risk in rGT., Methods: Rats were trained in a touch screen chamber to learn the relationships between 4 different light signals on the window of the screen and accompanied reward outcomes or punishments set up with different magnitudes and probabilities. Once they showed a stabilized pattern of preference upon free choice, rats were classified into risk-averse or risk-seeking groups. After performing the rGT, rats were decapitated, the mPFC and the NAc was dissected out, and NGS was performed with the total RNA extracted., Results: We found that 477 and 36 genes were differentially expressed (approximately 75 and 83% out of them were downregulated) in the mPFC and the NAc, respectively, in risk-seeking compared to risk-averse rats. Among those, we suggested a few top ranked genes that may contribute to promoting risky choices., Discussion and Conclusions: Our findings provide insights into transcriptional components underlying risky choices in rats.

Evidence about the involvement of genetic factors in the development of gambling disorder (GD) has been assessed. Among studies assessing heritability and biological vulnerability for GD, neurotrophin (NTF) genes have emerged as promising targets, since a growing literature showed a possible link between NTF and addiction-related disorders. Thus, we aimed to explore the role of NTF genes and GD with the hypothesis that some NTF gene polymorphisms could constitute biological risk factors. The sample included 166 patients with GD and 191 healthy controls. 36 single nucleotide polymorphisms (SNPs) from NTFs (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium (LD) and haplotype constructions were analyzed, in relationship with the presence of GD. Finally, regulatory elements overlapping the identified SNPs variants associated with GD were searched. The between groups comparisons of allele frequencies indicated that 6 SNPs were potentially associated with GD. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. The present study supports the involvement of the NTF family in the aetiopathogenesis of GD. An altered cross-regulation of different NTF members signalling pathways might be considered as a biological vulnerability factor for GD., (© 2022. The Author(s).)

Background: Despite abundant research on the potential causal influence of childhood maltreatment (CM) on psychological maladaptation in adulthood, almost none has implemented the discordant twin design as a means of examining the role of such experiences in later disordered gambling (DG) while accounting for genetic and family environmental confounds. The present study implemented such an approach to disentangle the potential causal and familial factors that may account for the association between CM and DG., Methods: Participants were 3750 twins from the Australian Twin Registry [Mage = 37.60 (s.d. = 2.31); 58% female]. CM and DG were assessed separately via two semi-structured telephone interviews. Random-intercept generalized linear mixed models were fit to the data; zygosity, sex, educational attainment, childhood psychiatric disorder, adult antisocial behavior, and alcohol use disorder (AUD) were included as covariates., Results: Neither quasi-causal nor familial effects of CM predicted DG after adjusting for covariates. Educational attainment appeared to reduce the risk of DG while AUD appeared to increase risk; evidence also emerged for familial effects of antisocial behavior on DG. Post-hoc analyses revealed a familial effect of CM on antisocial behavior, indicating that the association between CM and DG identified in unadjusted models and in prior studies may be accounted for by genetic and shared family environmental effects of antisociality., Conclusions: These findings add to the meager literature showing that CM does not exert a causal effect on DG, and present novel evidence that familial effects of antisocial behavior may account for the association between CM and DG identified in extant non-twin research.

In schizophrenia, subjects show reduced ability to evaluate and update risk/reward contingencies, showing correspondingly suboptimal performance in the Iowa gambling task. JNK signalling gene variants are associated with schizophrenia risk, and JNK modulates aspects of cognition. We therefore studied the performance of mice hemizygous for genetic deletion of the JNK activator MKK7 (Map2k7+/- mice) in a touchscreen version of the Iowa gambling task, additionally incorporating a novel contingency-switching stage. Map2k7+/- mice performed slightly better than wild-type (WT) littermates in acquisition and performance of the task. Although Map2k7+/- mice adapted well to subtle changes in risk/reward contingencies, they were profoundly impaired when the positions of 'best' and 'worst' choice selections were switched, and still avoided the previous 'worst' choice location weeks after the switch. This demonstrates a precise role for MKK7-JNK signalling in flexibility of risk/reward assessment and suggests that genetic variants affecting this molecular pathway may underlie impairment in this cognitive domain in schizophrenia. Importantly, this new contingency shift adaptation of the rodent touchscreen gambling task has translational utility for characterising these cognitive subprocesses in models of neuropsychiatric disorders., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background and Aims: Previous research has demonstrated phenotypical associations between disordered gambling (DG) and Big 5 personality traits, and a twin study suggested that shared genetic influences accounted for a substantial portion of this relation. The present study examined associations between DG and polygenic scores (PSs) for Big 5 traits to measure the shared genetic underpinnings of Big 5 personality traits and DG., Design: Zero-inflated negative binomial regression models estimated associations between Big 5 PSs and past-year and life-time assessments of DG in a longitudinally assessed population-based birth cohort., Setting: United Kingdom., Participants: A total of 4729 unrelated children of European ancestry from the Avon Longitudinal Study of Parents and Children (ALSPAC) with both phenotypical and genetic data., Measurements: Phenotypical outcomes included past-year assessment of DG using the problem gambling severity index (PGSI) and life-time assessment of DSM-IV pathological gambling symptoms (DPG) across the ages of 17, 20 and 24 years. Polygenic scores were derived for the Big 5 personality traits of agreeableness, extraversion, conscientiousness, openness and neuroticism using summary statistics from genome-wide association studies (GWAS)., Findings: PSs for agreeableness [β= - 0.25, standard error (SE) = 0.054, P = 3.031e-6, ΔR 2  = 0.008] and neuroticism (β=0.14, SE = 0.046, P = 0.0017, ΔR 2  = 0.002) significantly predicted PGSI scores over and above included covariates (i.e. sex and first five ancestral principal components). PSs for agreeableness (β= - 0.20, SE = 0.056, P = 0.00036, ΔR 2  = 0.003) and neuroticism, when interactions with age were taken into account (β = 0.29, SE = 0.090, P = 0.002, ΔR 2  = 0.004), also predicted DPG scores., Conclusions: Polygenic contributions to low agreeableness and high neuroticism appear to predict two measures of disordered gambling (problem gambling severity index and life-time assessment of DSM-IV pathological gambling symptoms). Polygenic scores for neuroticism interact with age to suggest that the positive association becomes stronger from adolescence through young adulthood., (© 2021 Society for the Study of Addiction.)

The multitude of gambling activities has given rise to heterogeneous ways of analyzing these behaviors and may partially underlie the lack of replication in gambling research. The current study used complementary analyses to investigate the structure, typology and etiology of gambling behaviors in a discovery sample of 2,116 twins (54.86% female; M age  = 24.90) and a replication sample of 619 siblings (30.37% female; M age  = 28.00). Our approach was twofold. First, we used confirmatory factor analyses to investigate the structure across the frequency of eight gambling activities. Second, we used factor mixture models to identify gambling frequency subtypes. We assessed associations with gambling frequency as well as conducted genetically informed analyses to estimate the role of genetic and environmental influences. Across samples, a two-factor model fit the data best, with a Common Gambling factor influencing all activities and a separate factor for Skill Gambling. Our study identified four gambling frequency subtypes, which resembled the typology from the Pathways Model. We found distinct demographic, psychiatric, behavioral and genetic risk profiles for the different gambling factors and subtypes with robust associations observed for male sex, risk-taking, sensation seeking, alcohol dependence and problem gambling. Controlling for shared genetic and environmental influences (via co-twin control modeling), we found that sensation seeking directly increased Common Gambling frequency. In sum, we illustrated the utility of multi-dimensional statistical techniques for disentangling the structure and typology from complex multivariate gambling data., (Published by Elsevier Ltd.)

The Naples High-Excitability (NHE) is a validated rat strain to model for a mesocortical variant of Attention Deficit Hyperactivity Disorder (ADHD). NHE rats' brains have a tuned-down cortical and a potentiated limbic loop (Zoratto et al., 2017). ADHD and comorbid pathological gambling (PG) involve similar deficits of prefrontal-striatal dialogue. This work aimed to understand if NHE rats (compared to normal random-bred rats, NRB) can be a useful model for gambling vulnerability in ADHD. Experiment 1 evaluated gambling proneness in NHE rats, namely attraction/avoidance in nose-poking for a "Large & Luck-Linked" (LLL) reward (versus a "Small & Sure" one, SS), when the probability of LLL delivery was progressively reduced. Experiment 2 assessed (by phMRI) differential responsivity of ventral (vStr) versus dorsal (dStr) striatum following a methylphenidate (MPH, 4 mg/kg I.P.) challenge. In NHE rats, reduced attraction by secondary cues (associated with uncertain, rarefying LLL delivery) comes along with little or no activation of dStr and enhanced activation of vStr by MPH. Together, such evidences from NHE rats indicate distinctive roles of ventral (enhanced value given to actual primary reward) and dorsal (lower encoding of repeated stimulus-reward associations into a habit) striatum. In conclusion, the dynamics of reward systems could link an attention deficit with a decreased vulnerability to pathological gambling., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gambling disorder is a common condition that was previously listed as an impulse control disorder, but is now considered a substance-related and addictive disorder. Gambling disorder has been associated with various untoward long-term outcomes including impaired quality of life, relationship break-ups, debt and mortgage foreclosure, and elevated risk of suicidality. This paper provides a concise primer on gambling disorder, with a special focus on its parallels with substance use disorders. We consider clinical presentations, comorbid expression, heritability, and treatment approaches (psychological and pharmacological). Lastly, we highlight new treatment directions suggested by the literature., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Professor Nicholas G. Martin, from QIMR Berghofer Medical Research Institute in Brisbane, Australia, is a world leader in the effort to understand the genetic architecture underlying disordered gambling. This article pays tribute to Nick and his almost two decades of gambling research, highlighting his many strengths, ranging from the use of ingenious recruitment approaches, twin study methods, genomewide association studies, to facilitating international collaborations.

Background and objectives: Although approaches combining behavioral genetics and neuroeconomics have advanced models of addiction, no study has synthesized these methods to elucidate mechanisms of competing risk-approachand risk-avoidance in social anxiety (SA). Grounded in dual-mode models of serotonergic systems and self-regulation, this study investigated associations between SA, serotonin transporter 5-HTT (LPR; rs25531) and receptor 5-HT1A genes, and risk-taking on behavioral and self-report measures. Design and methods: Young adults ( N  = 309) completed a neuroeconomic task measuring gambling attractiveness ( δ ), reward probability discrimination ( γ ), and risk attitudes ( α ). Risk genotypes included 5-HTT (LPR; rs25531) low-expression variants (SS/SL G /L G L G ), and 5-HT1A (rs6295) GG. Results: Path analysis revealed that SA related to increased gambling attractiveness, but only for 5-HT1A risk groups. Although the 5-HTT (LPR; rs25531) risk genotypes and self-reported SA predicted lower social risk-taking, high-SA individuals who exhibited more accurate reward probability discrimination ( γ ) reported taking increased social risks. Conclusion: In line with dual-mode models, results suggest that SA predicts behavioral risk-approach at the basic decision-making level, along with self-reported social risk-avoidance, modulated by serotonergic genotypes. High-SA individuals with more accurate assessments of reward probabilities may engage in greater social risk-taking, perhaps reflecting an adaptive tendency to approach feared situations.

Disordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994-1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N = 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling, OR = 0.93 [0.87, 0.99], p = .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG, OR = 1.54 [1.07, 2.21], p = .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.

Background and Aims: Some form of gambling can be observed in nearly every society, as the gratification felt upon winning in uncertain conditions is universal. A culturally distinct form of gambling, associated with a traditional sporting event of archery known as " teer ," is innate to the province of Meghalaya, India. The objective of this study was to find genetic variants underlying this unique form of behavioral addiction. To better understand game-based gambling, we studied genetic variants related to dopaminergic pathways and other genes previously linked to various psychological disorders., Methods: This study was carried out on a sample of 196 Indo-Aryan adults from Shillong, Meghalaya. Genotyping of glial cell line-derived neurotrophic factor (GDNF) polymorphisms was carried out using real-time PCR. We further investigated 32 single nucleotide polymorphisms located in the 3' UTR of additional genes of interest using an OpenArray ® real-time PCR platform., Results: Case-control analysis revealed a significant association between GDNF variant rs2973033 ( p  = .00864, χ 2  = 13.132, df  = 2) and contactin-associated protein-like 2 (CNTNAP2) variant rs2530311 ( p  = .0448, χ 2  = 13.132, df  = 2) with gambling., Discussion and Conclusions: Association of the GDNF gene with gambling could be attributed to its involvement in the development and survival of dopaminergic neurons. Our result is in good agreement with previous data indicating the role of GDNF in certain substance addictions. Several rare variants in the CNTNAP2 gene were also implicated in alcohol addiction in a previous study. This pilot study provides further support for the role of GDNF and CNTNAP2 in addiction behaviors.

Background and Aims: A single nucleotide polymorphism of A118G (SNP; rs1799971) in the opioid receptor μ-1 ( OPRM1 ) gene is a missense variant that influences the affinity of μ-opioid receptors. This study aimed to investigate the associations among the A118G polymorphism in the OPRM1 gene, psychiatric symptoms, and quantitative electroencephalography (qEEG) findings in patients with gambling disorder., Methods: Fifty-five male patients with gambling disorder aged between 18 and 65 years old participated in the study. The A118G polymorphism was genotyped into the AA, GA, and GG groups by the polymerase chain reaction/restriction fragment length polymorphism method. Resting-state qEEG was recorded with the eyes closed, and the absolute power of the delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) frequency bands was analyzed. Psychiatric symptoms, including depression, anxiety, impulsivity and severity of gambling, were assessed by a self-rating scale., Results: There were no significant differences in psychiatric symptoms among the three genotype groups (AA, GA, and GG). However, the frequency band power of qEEG showed significant differences among the three genotype groups. The absolute power of the beta and theta bands in the frontal lobe was higher in G allele carriers., Discussion and Conclusion: Based on the findings of this study, the polymorphism in the OPRM1 gene might affect the neurophysiological process in patients with gambling disorder.

The oxytocinergic system influences attentional bias towards emotional cues and feedback-based learning. Considering a tag single-nucleotide polymorphism (SNP) found through analysis of an intronic haplotype in the oxytocin receptor (OXTR) gene, we investigated the effect of oxytocin on risky decision-making via the Iowa Gambling Task (IGT). Young healthy males received intranasal oxytocin or placebo, and the IGT was performed where raw scores, net scores and total time were recorded, and ratio of advantageous to disadvantageous choices was calculated. Using PCR-pyrosequencing, a 761 bp target sequence in the OXTR gene was amplified and sequenced after the extraction of whole blood DNA. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all 14 SNPs in the intronic region were determined based on D' and LOD values, and rs2254295 with the highest LD was indicated as the tag SNP. GTT was shown to have the highest frequency among the found haplotypes. Oxytocin group and participants with the TT genotype demonstrated a significantly increased raw score, net score and advantageous choices, whereas the total time was not influenced remarkably. This means that oxytocin significantly reduced the risk taking in decision-making, and participants with the TT genotype had less premature or risky decisions than those with the CT and CC genotypes. rs2254295 may modulate the function or expression of the OXTR gene, implying that T allele may increase the expression of the OXTR gene compared to C allele. We suggest that oxytocin may remarkably moderate the risk attitude and its consequences during uncertain decision-making., (Copyright © 2019. Published by Elsevier B.V.)

Substance use and gambling participation during adolescence are correlated, both concurrently and over time. It is unclear, however, whether this association can be explained by common underlying genetic vulnerabilities or environmental factors. The present study explored the concurrent and longitudinal associations between substance use and gambling participation and their genetic and environmental underpinnings by late adolescence. Participants were 373 pairs of monozygotic and dizygotic twins. Self-reports of substance use and gambling participation were collected at Ages 17 and 19 years. Results showed concurrent associations between substance use and gambling participation as well as a small, but significant unidirectional longitudinal association over time from substance use to gambling participation. Common genetic factors largely accounted for the concurrent associations at Ages 17 and 19, as well as for the unidirectional longitudinal association between substance use and gambling participation. Substance use and gambling participation share a common genetic component that account for most of their concurrent and longitudinal links during late adolescence. However, these behaviors are also influenced by specific environmental factors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date., Methods: Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972-79) and 4764 (mean age 37.7, born 1964-71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women., Results: In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45-76%) and unique environmental (40%; 95% CI 24-56%), but not shared environmental contributions (0%; 95% CI 0-0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD., Conclusions: Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.

Objectives: Most of the addiction studies focus on very specific aspects of addictions, often with contradictory results, and integrated studies are quite rare. Experimental studies comparing underlying mechanisms of addictions and analyzing data from an integrative psychological and genetic perspective are almost nonexistent. The aim of the present paper is to describe the research protocol of the Psychological and Genetic Factors of Addictive Behaviors (PGA) study, which applies an integrative approach to understanding the acquisition, development, and maintenance of addictive behaviors., Methods: A wide-spectrum national study was carried out. Data were collected from 3,003 adolescents. Addictions to both psychoactive substances and behaviors were thoroughly assessed via psychometrically robust scales, which also included assessment related to a wide range of related psychological dimensions. Additionally, a DNA sample was also collected from participants., Results: The paper presents the detailed methodology of the PGA study. Data collection procedures, instrumentation, and the analytical approach used to attain the research objectives are described., Conclusions: Future plans, along with potential contributions of the PGA study, are also discussed. It is envisaged that the study will provide a unique opportunity to test possible mechanisms and causal pathways mediating the associations of genetic factors, psychological characteristics, and addictions., (© 2018 John Wiley & Sons, Ltd.)

Rationale: Serotonin (5-HT) plays a key role in different aspects of value-based decision-making. A recent framework proposed that tonic 5-HT (together with dopamine, DA) codes future average reward expectations, providing a baseline against which possible choice outcomes are compared to guide decision-making., Objectives: To test whether high 5-HT levels decrease loss aversion, risk-seeking for gains, and risk-seeking for losses., Methods: In a first session, 611 participants were genotyped for 5-HTTLPR and performed a mixed gambles (MGA) task and two probability discounting tasks for gains and losses, respectively (PDG/PDL). Afterwards, a subsample of 105 participants (44 with S/S, 6 with S/L, 55 with L/L genotype) completed the pharmacological study using a crossover design with tryptophan depletion (ATD), loading (ATL), and balanced (BAL) conditions. The same decision constructs were assessed., Results: We found increased risk-seeking for losses in S/S compared to L/L individuals at the first visit (p = 0.002). Neither tryptophan depletion nor loading affected decision-making, nor did we observe an interaction between intervention and 5-HTTLPR genotype., Conclusion: Our data do not support the idea that transient changes of tonic 5-HT affect value-based decision-making. We provide evidence for an association of 5-HTTLPR with risk-seeking for losses, independent of acute 5-HT levels. This indicates that the association of 5-HTTLPR and risk-seeking for losses is mediated via other mechanisms, possibly by differences in the structural development of neural circuits of the 5-HT system during early life phases.

Should excessive and problematic engagement in nonsubstance use behaviors be mental disorders? The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) repositioned gambling disorder in the substance use disorders section and introduced Internet gaming disorder in the research appendix; the International Classification of Diseases (ICD-11) is also considering it. This article outlines pros and cons of considering behavioral addictions as mental disorders and also reviews the DSM-5 decision-making processes. It focuses on three conditions: gambling disorder, Internet gaming disorder (IGD), and Internet addiction (IA). We detail assessment methods and prevalence rates for these conditions and outline psychiatric comorbidities, demographic and biological risk factors, and promising treatment approaches. We also briefly discuss other putative behavioral addictions: eating/food, sex, exercise, shopping, and tanning "addictions." Overall, data are inconclusive, and consistent terminology and methodology are needed to define and evaluate these conditions more fully prior to considering them mental disorders.

Social changes, such as the expansion of legal forms of gambling, can influence not only the prevalence of gambling, but can also shape the relative importance of genetic and environmental contributions to individual differences in the propensity to gamble. In the present study, I examined differences in the prevalence and in the relative contribution of genetic and environmental factors to gambling involvement in the United States in 1962 versus 2002. The data came from two sources: (1) a survey of 839 17-year-old same-sex twin pairs from the National Merit Scholarship Qualifying Test twin study, and (2) an interview of 477 18- to 26-year-old same-sex twin pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Similar measures of gambling participation were included in the two studies. Evidence for a genotype-by-time interaction was evaluated by testing whether the contribution of genetic influences was greater in the more recently born cohort of twins. Despite the major changes in the gambling landscape over the intervening 40 years, there was no evidence for such an interaction. The contribution of genetic factors and environmental factors did not significantly differ and there was no evidence for genetic influences at either time point. Instead, the variation in the propensity to gamble was explained nearly equally by common and unique environmental factors. Explanations for this surprising finding are discussed.

Gambling behaviors tend to increase in prevalence from late adolescence to young adulthood, and the underlying genetic and environmental influences during this period remain largely understudied. We examined the genetic and environmental influences on gambling behaviors contributing to stability and change from ages 18 to 25 in a longitudinal, behavioral genetic mixed-sex twin study design. Participants were enrolled in the Minnesota Twin Family Study. A range of gambling behaviors (maximum frequency, average frequency, money lost, and gambling problems) were assessed at ages 18 and 25. The results of our study support the following conclusions: (a) the genetic and environmental factors impacting a range of gambling behaviors are largely similar in men and women, (b) genetic factors increase in influence from 18 to 25 (21% at age 18 to 57% at age 25), (c) shared environmental factors are influential at age 18, but tend to decrease from ages 18 to 25 (55% at age 18 to 10% at age 25), and (d) nonshared environmental influences are similarly significant and are small to moderate in magnitude at both ages. The findings add to a small yet important research area regarding determinants of youth gambling behaviors and have the potential to inform prevention and intervention efforts. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Gambling Disorder (GD) is characterized by excessive gambling despite adverse consequences on individual functioning. In spite of some positive findings, it is difficult to draw any conclusion on the genetics of GD. Indeed, beyond DNA sequence variation, other regulatory mechanisms (like those that engage epigenetics) may explain gene alterations in this addictive disease. Wistar male rats underwent an operant task for the evaluation of individual propensity to gamble. Few rats, after having learnt to prefer nose-poking for a large over a small food reward, were sacrificed to obtain a baseline profile of gene expression at both central and peripheral levels. In the remaining rats, probability of occurrence of large-reward delivery decreased progressively to very low levels. Thus, rats were faced with temptation to "gamble", i.e. to nose-poke for a binge reward, whose delivery was omitted the majority of times. After 3weeks of testing, rats showing a clear-cut profile of either gambling proneness or aversion were selected and sacrificed after the last session. A selective down-regulation of i) serotonin transporter in prefrontal cortex, ii) tyrosine hydroxylase in ventral striatum, iii) dopamine transporter in lymphocytes was evidenced in "gambler" vs "non-gambler" rats. The exposure to such operant task (compared to home-cage alone) modulated ventrostriatal but not prefrontal genes. A consistent increase of DNA methylation, in one specific CpG site at serotonin transporter gene, was evident in prefrontal cortex of "gambler" rats. Elucidation of epigenetic changes occurring during GD progression may pave the way to the development of new therapeutic strategies through specific modulation of epigenetic factors., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

An optimal biochemical marker for addiction would be some easily traced molecules in body specimens, which indicates indulgent addictive behaviors, or susceptibility to certain addictive stimuli. In this chapter, we discussed existing literature about possible biomarkers, and classified them into three categories: origin forms and metabolites of substances, markers from biochemical responses to certain addiction, and genetic and epigenetic biomarkers suggesting susceptibility to addiction. In every category, we examined studies concerning certain type of addiction one by one, with focuses mainly on opiates, psychostimulants, and pathological gambling. Several promising molecules were highlighted, including those of neurotrophic factors, inflammatory factors, and indicators of vascular injury, and genetic and epigenetic biomarkers such as serum miRNAs. DNA methylation signatures and signal nucleotide polymorphism of candidate gene underlying the addiction.

Similar symptomatology manifestations and high co-morbidity in substance and non-substance addictions suggest that there may be a common pathogenesis between them. Associated with impulse control and emotional processing, the monoamine neurotransmitter system genes are suggested to be related to both substance and non-substance addictions, such as dopamine (DA) system, 5-hydroxytryptamine/serotonin (5-HT) system, the endogenous opioid system and so on. Here we reviewed the similarities and differences in genetics between classic substance addiction and common types of non-substance addiction, e.g. pathological gambling, Internet addiction, binge-eating disorder etc. It is necessary to systematically compare genetic mechanisms of non-substance addiction and substance addiction, which could reveal similarities and differences of substance addiction and non-addictive substances essentially, enhance our understanding of addiction theory and improve clinical practice with research results.

Background: Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence., Methods: Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence., Results: No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status., Conclusions: The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background and aims Corticostriatal-limbic neurocircuitry, emotional and motivational processing, dopaminergic and noradrenergic systems and genetic factors have all been implicated in pathological gambling (PG). However, allelic variants of genes influencing dopaminergic and noradrenergic neurotransmitters have not been investigated with respect to the neural correlates of emotional and motivational states in PG. Dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine; the T allele of a functional single-nucleotide polymorphism rs1611115 (C-1021T) in the DBH gene is associated with less DBH activity and has been linked to emotional processes and addiction. Here, we investigate the influence of rs1611115 on the neural correlates of emotional and motivational processing in PG and healthy comparison (HC) participants. Methods While undergoing functional magnetic resonance imaging, 18 PG and 25 HC participants, all European Americans, viewed gambling-, sad-, and cocaine-related videotapes. Analyses focused on brain activation differences related to DBH genotype (CC/T-carrier [i.e., CT and TT]) and condition (sad/gambling/cocaine). Results CC participants demonstrated greater recruitment of corticostriatal-limbic regions, relative to T-carriers. DBH variants were also associated with altered corticostriatal-limbic activations across the different videotape conditions, and this association appeared to be driven by greater activation in CC participants relative to T-carriers during the sad condition. CC relative to T-carrier subjects also reported greater subjective sadness to the sad videotapes. Conclusions Individual differences in genetic composition linked to aminergic function contribute significantly to emotional regulation across diagnostic groups and warrant further investigation in PG.

Our everyday-life comprises a multitude of decisions that we take whilst trying to maximize advantageous outcomes, limit risks and update current needs. The cognitive processes that guide decision making as well as the brain circuits they are based on are only poorly understood. Numerous studies point to a potential role of dopamine and nicotine in decision making but less is known about their interactions. Here, 26 healthy male subjects performed the Iowa Gambling Task (IGT) in two sessions following the administration of either nicotine or placebo. Striatal dopamine transporter (DAT) binding was measured by single-photon emission computed tomography (SPECT). Results indicate that lower DAT levels were associated with better performance in the IGT (p=0.0004). Cognitive modelling analysis using the prospect valence learning (PVL) model indicated that low DAT subjects' performance deteriorated following nicotine administration as indicated by an increased learning rate and a decreased response consistency. Our results shed light on the neurochemistry underlying reward-based decision making in humans by demonstrating a significant interaction between nicotine and the DAT. The observed interaction is consistent with the hypothesized associations between DAT expression and extracellular dopamine levels, suggestive of an inverted U-shape relationship between baseline dopamine and magnitude in response to a pro-dopaminergic compound. Our findings are of particular interest in the context of psychiatric disorders where aberrant decision making represents a part of the core symptomatology, such as addiction, schizophrenia or depression., (Copyright © 2016. Published by Elsevier B.V.)

Previous studies have demonstrated increased risk-taking in adolescents with Conduct Disorder (CD) compared with typically developing controls. Increased risk-taking may partly mediate the pathway from genetic or environmental risk to CD. We investigated the familial basis of risk-taking by examining whether the unaffected relatives of CD probands (n = 22) showed heightened risk-taking in a gambling task, in common with affected probands (n = 44). Adolescents with CD were more likely to select risky options than the typically developing controls (n = 37) and unaffected relatives. Our findings confirm the association between CD and increased risk-taking, but suggest that this decision-making style may not have a familial basis.

Background/aims: Effective treatment strategies are needed for the treatment of pathological gambling (PG). The efficacy of as-needed naltrexone was assessed in a single-centre, randomised, double-blind, placebo-controlled trial., Methods: The participants (n = 101) received either as-needed placebo or naltrexone (50 mg) and psychosocial support for 20 weeks. The primary outcome measure was the severity of PG assessed by the Yale-Brown Obsessive Compulsive Scale adapted for PG (PG-YBOCS). Secondary gambling-related outcome measures included thoughts/urges and behaviour subscales of PG-YBOCS as well as the highest daily expenditure and gambling frequency. In addition, RAND-36 scales of emotional well-being and social functioning were used as outcomes. The results were analysed using the intention-to-treat principle and linear random effects modelling., Results: No significant treatment group differences were found. In an exploratory analysis, emotional well-being increased in a subgroup of participants with AA genotype of opioid receptor, mu 1 (OPRM1) A118G polymorphism (p = 0.02)., Conclusion: Overall, the as-needed naltrexone may not provide substantial additional benefit for PG patients receiving psychosocial support. Replication by larger scale studies is warranted to further evaluate naltrexone administration schedules for the treatment of PG and the role of OPRM1., (© 2015 S. Karger AG, Basel.)

Background: Several studies point towards a role for dopaminergic circuits in the pathophysiology of problematic gambling behavior. The aim of the present study was to investigate alterations of DNA methylation in the dopamine D2 receptor (DRD2)-gene in participants with pathologic gambling behavior., Results: The study was part of a large epidemiological study on pathologic gambling in Germany. DNA methylation of the DRD2-gene was analyzed from oral mucosa using next generation bisulfite sequencing. The final sample included 77 participants. The study showed significantly lower methylation levels of the DRD2-gene in abstinent patients over the last 12 or 30months compared to non-abstinent participants. Furthermore, participants without any treatment utilization regarding gambling behavior showed higher DRD2-gene methylation levels compared to treatment-seeking participants., Conclusions: DNA-methylation patterns in the DRD2-gene were altered in respect to abstinence over a 12-month or a 30-month period and to treatment utilization with higher methylation levels in non-abstinent and participants without treatment-seeking behavior. These results point towards a pathophysiologic relevance of altered DRD2-expression due to changes of DNA methylation in pathologic gambling behavior., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Loss aversion is the tendency to overweight losses compared with gains in decision situations. Several studies have investigated the neurobiological background of this phenomenon and it was found that activation in the mesolimbic-mesocortical dopamine system during a gambling decision correlates with loss aversion. In a behavioral experiment with N = 143 subjects, the present study investigates the influence of 2 functional single-nucleotide polymorphisms on the BDNF gene (BDNF Val66Met polymorphism) and ANKK1 gene (DRD2 Taq1a/ANKK1 polymorphism), that are known to affect the dopamine system, on loss aversion. Additionally, associations of alexithymia, a personality construct describing the disability to consciously experience emotions in the self, with loss aversion and with the mentioned polymorphisms were assessed using the TAS-20 questionnaire, to replicate associations that have been reported before. Results revealed a significant interaction effect of the 2 polymorphisms on loss aversion. Carriers of the genetic constellation 66Met+/A1+ had the lowest loss aversion scores, compared with all other allelic groups. According to the literature this allelic configuration is characterized by a relatively low D2/3 receptor binding in the striatum and an impaired activity-dependent secretion of BDNF. This is the first study showing that loss aversion is related to naturally occurring differences in dopamine function., ((c) 2015 APA, all rights reserved).)

Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Epidemiological studies strongly suggest that genetic factors operate at all steps of addictions, including vulnerability to initiation, continued use, and propensity to become dependent. Several studies have been popular to investigate the relative contributions of genetic and environmental factors, including the availability of and exposure to a substance, and shared and unique environments. The genetic influence on addiction has proved to be substantial, and heritabilities for most addictive disorders are moderate to high. In this work we evaluate the current status of data that analyzed genetic contribution in addictions.

Background: Individuals with cocaine and gambling addictions exhibit cognitive flexibility deficits that may underlie persistence of harmful behaviours., Aims: We investigated the neural substrates of cognitive inflexibility in cocaine users v. pathological gamblers, aiming to disambiguate common mechanisms v. cocaine effects., Method: Eighteen cocaine users, 18 pathological gamblers and 18 controls performed a probabilistic reversal learning task during functional magnetic resonance imaging, and were genotyped for the DRD2/ANKK Taq1A polymorphism., Results: Cocaine users and pathological gamblers exhibited reduced ventrolateral prefrontal cortex (PFC) signal during reversal shifting. Cocaine users further showed increased dorsomedial PFC (dmPFC) activation relative to pathological gamblers during perseveration, and decreased dorsolateral PFC activation relative to pathological gamblers and controls during shifting. Preliminary genetic findings indicated that cocaine users carrying the DRD2/ANKK Taq1A1+ genotype may derive unique stimulatory effects on shifting-related ventrolateral PFC signal., Conclusions: Reduced ventrolateral PFC activation during shifting may constitute a common neural marker across gambling and cocaine addictions. Additional cocaine-related effects relate to a wider pattern of task-related dysregulation, reflected in signal abnormalities in dorsolateral and dmPFC., (© The Royal College of Psychiatrists 2015.)

Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.

Previous research has demonstrated that local area characteristics (such as disadvantage and gambling outlet density) and genetic risk factors are associated with gambling involvement and disordered gambling. These 2 lines of research were brought together in the present study by examining the extent to which genetic contributions to individual differences in gambling involvement and disorder contributed to being exposed to, and were also accentuated by, local area disadvantage. Participants were members of the national community-based Australian Twin Registry who completed a telephone interview in which the past-year frequency of gambling and symptoms of disordered gambling were assessed. Indicators of local area disadvantage were based on census data matched to the participants' postal codes. Univariate biometric model-fitting revealed that exposure to area disadvantage was partially explained by genetic factors. Bivariate biometric model-fitting was conducted to examine the evidence for gene-environment interaction while accounting for gene-environment correlation. These analyses demonstrated that: (a) a small portion of the genetic propensity to gamble was explained by moving to or remaining in a disadvantaged area, and (b) the remaining genetic and unique environmental variation in the frequency of participating in electronic machine gambling (among men and women) and symptoms of disordered gambling (among women) was greater in more disadvantaged localities. As the gambling industry continues to grow, it will be important to take into account the multiple contexts in which problematic gambling behavior can emerge-from genes to geography-as well as the ways in which such contexts may interact with each other., ((c) 2015 APA, all rights reserved).)

Disordered gambling and alcohol dependence are influenced by unique and shared genetic factors. Although the evidence is mixed, some research has linked catechol-O-methyltransferase (COMT) rs4680 (or COMT Val158Met) to the development of gambling or drinking problems; however, no molecular genetic study has jointly examined gambling and drinking problems. Furthermore, the majority of past studies examined gambling or drinking problems using a case-control design. The purpose of the current study was to examine associations of COMT rs4680 with dimensionally and categorically measured gambling and drinking problems in a nonclinical sample (139 Caucasian adults). The current study found that COMT rs4680 was related to both dimensionally and categorically measured gambling and drinking problems. It appears that the COMT Met/Met genotype may be a genetic risk factor that contributes to the development of both gambling and drinking problems.

Importance: Because of shared characteristics, pathological gambling (PG) has been variously conceptualized as an obsessive-compulsive (OC) spectrum disorder or as an addictive disorder. Prior community-based studies have not systematically determined the association between PG and OC features and whether common genetic factors contribute to both conditions., Objective: To examine the association and genetic correlation between PG and OC features., Design, Setting, and Participants: We performed a latent class analysis (LCA) of OC features, cross-sectional tests of association, and classic twin genetic analysis using results of telephone interviews conducted from March 2002 through November 2003. Participants included 1675 male twin pairs from the Vietnam Era Twin Registry, aged 45 to 60 years., Main Outcomes and Measures: Ten OC features were queried and used to derive OC classes identified via LCA., Results: The best-fitting LCA model identified the following 4 OC classes: unaffected (class 1), ritual/symmetry compulsions (class 2), germ/contamination obsessions (class 3), and severe OC (class 4). All PG symptoms were more common in class 4 OC and 6 of 10 PG symptoms were significantly more common in class 4 OC (P < .01). Participants in the severe class were most likely to have 4 or more DSM-IV or DSM-5 PG diagnostic criteria (odds ratio, 3.8 [95% CI, 1.8-8.2]). The genetic correlation between phenotypes was 0.44 (95% CI, 0.16-0.75)., Conclusions and Relevance: The association between OC features and diagnostic criteria for PG highlights a role of obsessions and compulsivity in PG, and the lifetime co-occurrence of these disorders results in part from common genetic variance. Phenotypic and genetic overlap between OC features and PG add to our understanding of the most appropriate classification of PG and offers insights for treatment development.

This study investigates the possible relationship between pathological gambling (PG) and potential spectrum disorders including the DSM-IV impulse control disorders (intermittent explosive disorder, kleptomania, pyromania, trichotillomania) and several non-DSM disorders (compulsive buying disorder, compulsive sexual behavior, Internet addiction). PG probands, controls, and their first-degree relatives were assessed with instruments of known reliability. Detailed family history information was collected on relatives who were deceased or unavailable. Best estimate diagnoses were assigned blind to family status. The results were analyzed using logistic regression by the method of generalized estimating equations. The sample included 95 probands with PG, 91 controls, and 1075 first-degree relatives (537 PG, 538 controls). Compulsive buying disorder and having "any spectrum disorder" were more frequent in the PG probands and their first-degree relatives vs. controls and their relatives. Spectrum disorders were significantly more prevalent among PG relatives compared to control relatives (adjusted OR=8.37), though much of this difference was attributable to the contribution from compulsive buying disorder. We conclude that compulsive buying disorder is likely part of familial PG spectrum., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Gambling disorder, recognized by the DSM-5 as a behavioral addiction, affects .4-1.6% of adults worldwide, and is highly comorbid with other mental health disorders, particularly substance use disorders (SUDs)., Objectives: To provide a concise primer on the relationship between gambling disorder and SUDs, focusing on phenomenology/clinical presentation, co-morbidity, familiality, cognition, neuroanatomy/neurochemistry, and treatment., Methods: Selective review of the literature., Results: Scientific evidence shows that gambling and SUDs have consistently high rates of comorbidity, similar clinical presentations, and some genetic and physiological overlap. Several treatment approaches show promise for gambling disorder, some of which have previously been effective for SUDs., Scientific Significance: It is hoped that recognition of overlap between gambling disorder and SUDs in terms of phenomenology and neurobiology will signal novel treatment approaches and raise the profile of this neglected condition., (© American Academy of Addiction Psychiatry.)

The premise that an association between an earlier age of gambling initiation and the later development of disordered gambling is causal has not yet been empirically examined. The current study used a multilevel discordant twin design to examine the nature of this association. Participants were 3,546 same-sex twins (mean age = 37.7 years) from the Australian Twin Registry who completed a telephone interview that included an extensive assessment of gambling and related behaviors. Multilevel models were employed to estimate individual (within-twin-pair comparison) and family level (between-twin-pair comparison) effects, as well as the cross-level interaction between these effects. Family-level effects (genetic or environmental factors shared by family members) of age of gambling initiation robustly predicted later adult gambling frequency and disorder; the evidence for individual-level effects (unique factors not shared by family members, including a potentially causal effect of earlier age of gambling onset) was less robust. The results of this study suggest that the relation between earlier age of gambling initiation and later gambling involvement and disorder is primarily noncausal; efforts to delay the onset of gambling among young people may not necessarily reduce the number who later go on to develop gambling-related problems.

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG., (© The Author(s) 2014.)

This study examined the genetic and environmental architecture of early gambling involvement and substance use to determine whether genetic or environmental factors that contribute to substance use also put young adolescents at risk for early involvement in gambling. Self-reports of substance use and gambling involvement were collected at age 13 years from 279 Monozygotic and Dizygotic twin pairs. Univariate ACE modeling revealed that genetic and nonshared environmental factors almost equally accounted for gambling involvement, with no contribution from shared environmental factors. In contrast, both shared and nonshared environmental factors played important roles in substance use; the contribution of genetic factors was also substantial. Bivariate analyses identified a significant, albeit modest, overlap between the genetic influence on gambling involvement and the genetic influence on substance use. The results shed light on the etiology of early gambling involvement and substance use, suggesting that preventive interventions targeting common risk factors may also need to be complemented by modules that are specific to each behavior.

Aims: Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence., Design: Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence., Setting: Computer-assisted telephone interviews in the community., Participants: Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry., Measurements: Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule., Findings: All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA  = 0.22; 95% confidence interval (CI) = 0.10-0.34] and non-shared environmental components (environmental correlation rE  = 0.24; 95% CI = 0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA  = 0.32; 95% CI = 0.05-1.0; rE  = 0.36; 95% CI = 0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA  = 0.58; 95% CI = 0.45-0.73)., Conclusions: Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders., (© 2013 Society for the Study of Addiction.)

Objective: Pathological gambling is a major public health problem. We sought to examine the familiality of pathological gambling and determine patterns of familial aggregation of disorders., Method: We assessed probands with DSM-IV pathological gambling, controls, and their first-degree relatives. Detailed family history information was collected on relatives who were deceased or unavailable., Results: Ninety-five pathological gambling probands, 91 controls, and their 1,075 first-degree relatives over age 18 (537 relatives of pathological gambling probands, 538 relatives of controls) were evaluated between February 2005 and June 2010. Relatives were assessed blind to proband status. Best estimate diagnoses were assigned. Rates of lifetime pathological gambling (definite/probable) was significantly greater among the first-degree relatives of probands with pathological gambling than among comparison relatives (11% vs 1%, OR = 8.19, P < .001). The prevalence of pathological gambling and subclinical pathological gambling combined was 16% and 3% in case and control relatives, respectively (OR = 6.57, P < .001). Pathological gambling relatives had higher rates of major depression (OR = 1.49, P < .05), bipolar disorder (OR = 3.82, P < .05), any mood disorder (OR = 1.59, P < .05), social anxiety disorder (OR = 4.76, P < .01), any substance use disorder (OR = 1.47, P < .05), posttraumatic stress disorder (OR = 2.59, P < .05), and antisocial personality disorder (OR = 3.72, P < .001). Antisocial personality disorder (OR = 3.12, P < .01), social anxiety disorder (OR = 4.15, P < .01), and posttraumatic stress disorder (OR = 2.85, P < .05) were more frequent in case relatives independent of the presence of pathological gambling. Age at onset of pathological gambling in case probands (< 40 years/≥ 40 years) was not related to familiality in their first-degree relatives (OR = 1.03, P = .927)., Conclusions: Pathological gambling is familial. Mood and substance use disorders may emerge as a consequence of the pathological gambling or as a more complex syndrome. In contrast, antisocial personality disorder, social anxiety disorder, and posttraumatic stress disorder may share a common familial etiology with pathological gambling. The phenotype may extend beyond pathological gambling to include subclinical forms of the disorder., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

There is a paucity of research examining prospective predictors of problem gambling. The current study utilised a large longitudinal data set (N = 2328) to examine a large range of adolescent risk and protective factors for problem gambling in young adulthood. These risk and protective factors covered the domains of the community, family, school, peer group and individual. Numerous predictors associated with the family, school and peer-individual were statistically significant in analyses adjusted for gender and age. However, in the fully adjusted multivariate analyses, only two predictors were statistically significant. Within this model, gender (female) was associated with a reduced risk of young adult problem gambling, while family rewards for prosocial involvement moderated the risk relationship between adolescent alcohol use and young adult problem gambling. These findings highlight the importance of adolescent alcohol use and family environment as potentially modifiable predictors of young adult problem gambling., (Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)