Dopamine Genes and Pathological Gambling in Discordant Sib-Pairs

Pathological gambling (PG) is an impulse control disorder that has been considered as a behavioral addiction. Recent studies have suggested the involvement of the dopaminergic system in addictions and impulse control disorders and associations of dopamine receptor genes (DRD1, DRD2, and DRD4) and PG have been reported. In the present study, 140 sib-pairs discordant for the diagnosis of PG (70 males and 70 females on each group) were recruited through the Gambling Outpatient Unit at the Institute of Psychiatry, University of Sao Paulo and were assessed by trained psychiatrists. A family-based association design was chosen to prevent population stratification. All subjects were genotyped for dopamine receptor genes (DRD1 -800 T/C, DRD2 TaqIA RFLP, DRD3 Ser9Gly, DRD4 48bp exon III VNTR, DRD5 (CA) repeat) and the dopamine transporter gene (SCL6A3 40 bp VNTR). Our results suggest the association of PG with DRD1 -800 T/C allele T (P = .03).     

Genetics of pathological gambling

Pathological gambling (PG) is an impulse control disorder and a model behavioral addiction. Familial factors have been observed in clinical studies of pathological gamblers, and twin studies have demonstrated a genetic influence contributing to the development of PG. Serotonergic, noradrenergic, and dopaminergic dysfunction have been reported as biological factors contributing to the pathophysiology of PG. Molecular genetic techniques have been used to investigate the role of genetic factors in PG. Molecular genetic research has identified specific allele variants of candidate genes corresponding to these neurotransmitter systems to be associated with PG. Associations have been reported between pathological gamblers and allele variants of polymorphisms at dopamine receptor genes, the serotonin transporter gene, and the monoamine-oxidase A gene. Although preliminary data suggest that some of these differences are gender-specific, more research needs to be performed to substantiate gender-specific genetic contributions to the development of pathological gambling. The review of the current findings on genetics of PG suggests that liability to PG is in part mediated by genetic factors. Additional studies are needed to replicate and extend these findings, as well as to better understand the influence of specific allelic variants to differences in biological and behavioral functioning.     

Externalizing Problem Behavior in Adolescence: Parenting Interacting With DAT1 and DRD4 Genes

This study extends previous gene‐by‐environment (G × E) research through design and methodological advances and examines alternative hypotheses of diathesis stress, vantage sensitivity, and differential susceptibility. In a sample of 984 adolescents and their parents, we examined whether effects of parental support, proactive, punitive, harsh punitive, and psychological control on externalizing problem behavior are moderated by adolescents' genotype for the dopamine transporter (DAT1) or receptor D4 (DRD4) gene. Results provided evidence for main effects of parenting behavior and DRD4, and multiple interaction effects of which one survived Bonferroni correction. Adolescents carrying a long DRD4 variant were more susceptible to the effects of parental proactive control on aggression, for better and for worse. Critical considerations were made regarding the complexity of G × E research.     

Prevalence of Problem and Pathological Gambling in Parkinson’s Disease

Pathological gambling (PG) has been identified in patients with Parkinson’s disease (PD) treated with dopamine agonists suggesting that dysregulation of brain dopaminergic activity may contribute to the development of gambling problems. The current study was undertaken to further establish the prevalence of problem and PG in patients with PD, identify any clinical correlates, and determine if psychiatric or substance use co-morbidity contributes to the increased prevalence of problem and PG. A cross-sectional survey of 140 serially recruited moderate to severe PD patients was undertaken utilizing the Canadian Problem Gambling Index, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test, Beck Depression Inventory, Beck Anxiety Inventory, and Mini-Mental State Exam augmented by chart review, completed over an 8 month period. The 12 month prevalence of problem and PG in PD was 9.3% compared to 1.6% in the general population within a comparably aged sample. The increased prevalence of problem and PG in the PD group was related to dopamine agonist use and younger age, but not co-morbidity. Most subjects with problem and PG reported their gambling increased after being diagnosed with PD and starting treatment. The results suggest that brain dopaminergic activity is involved in the underlying neurobiology of problem and PG.     

Genetic Studies of Pathological Gambling: A Review of Methodology and Analyses of Data from the Vietnam Era Twin Registry

Twin studies represent an important and powerful approach to estimating the relative contributions of environmental and genetic factors to the expression of psychiatric illnesses. In this article, we first explain the rationale for using large populations of monozygotic and dizygotic twin pairs to estimate genetic and environmental contributions to a disorder and the statistical modeling associated with this approach. We then review results from studies of the Vietnam Era Twin Registry that use this methodology to examine the etiology of pathological gambling (PG) behaviors. The results provide strong evidence for genetic contributions to the development of PG in men and set the foundation for future studies aimed at identifying the manner in which specific genes and environmental factors individually and in conjunction contribute to PG.     

Reasons for Starting and Continuing Gambling in a Mixed Ethnic Community Sample of Pathological and Non-problem Gamblers

Very few studies have investigated motivational differences between pathological gamblers (PG) and non-problem gamblers (NPG), or between men and women. Motives for starting gambling have not been distinguished from motives for continuing gambling. From a community survey questionnaire listing reasons generated from the population studied, the motives of 103 current PG met the DSM-IV-TR criteria of five or more symptoms within the 12 months to October 2004. NPG assented to less than three symptoms. Generally, PG had significantly stronger motives than NPG and preferred continuous forms of gambling. There were no overall gender differences in motives, but electronic gaming machines and bingo were the primary choices for female PG. Gambling to escape from stress and troubles increased for PG but not for NPG, while gambling for social reasons decreased for both groups. Because of disproportionate numbers of PG and NPG in the Caucasian, Maori, Pacific Island and Asian groups, ethnic differences were not examined. The findings supported some aspects of theories of gambling motivation. Lowering stress for PG, raising community awareness of the risk of gambling to socialize and undertaking longitudinal research in community samples were suggested.     

Division of Labor,Gender Ideology,and Marital Satisfaction in East Asia

Using data from the 2006 Family Module of the East Asian Social Survey (N = 3,096), this article examines associations of marital satisfaction with divisions of housework and gender ideology in four East Asian societies: urban China, Japan, South Korea, and Taiwan. Compared with Japanese and Korean married women and men, Chinese and Taiwanese spouses were more satisfied with their marriage and had more egalitarian divisions of housework, but simultaneously they held less egalitarian gender ideologies. Multivariate analyses showed that relative share of housework was negatively associated with marital satisfaction for Japanese and Korean men and for Korean and Taiwanese women. Egalitarian gender ideology was significantly associated with lower marital satisfaction only among Taiwanese women. In addition, the negative association between housework and marital satisfaction was more pronounced for Taiwanese women who espoused more egalitarian gender ideologies. The authors discuss how differences in macro‐level social contexts explain these cross‐society variations.     

Prevalence of Sexual Dysfunction and Associated Risk Factors in Middle-Aged and Elderly Korean Men in Primary Care

Although several studies have individually investigated the risk factors for erectile dysfunction (ED), premature ejaculation (PE), and late-onset hypogonadism (LOH), few studies have considered ED, PE, and LOH as categories of sexual dysfunction (SD) within the same population. We therefore aimed to investigate the prevalence of SD and its associated risk factors among men in primary care. Study participants were enrolled by 18 family physicians from 15 hospital-based family practices in Korea between August 2010 and May 2011. Participants answered a questionnaire regarding their demographic characteristics and lifestyle factors as well as the Korean versions of the Androgen Deficiency in the Aging Male, the International Index of Erectile Function, and the Premature Ejaculation Diagnostic Tool questionnaires. SD prevalence was 64.9% among study participants who were ≥ 40 years of age. ED prevalence was 43.7%, PE prevalence was 38.6%, and LOH prevalence was 16.8%. SD prevalence was significantly associated with increased age, overweight, hypertension, diabetes, and depression. These findings highlight the importance of screening questions for SD in primary care, especially among older male patients with the identified risk factors.     

l-Arginine and tetrahydrobiopterin,but not sodium nitrite partially restored erectile dysfunction in aged rats

This paper gives an overview of our own studies and the literature on the biosynthesis and metabolism of estrogens in elderly men, the estrogen action in the male, and the clinical usefulness of estrogen therapy, including the phytoestrogens. Finally, the paper includes a short review of our knowledge of xenoestrogens and men's sexual health. A strong estrogen-deficient status is seen in male patients with mutations of the estrogen receptors or in cases of deviations of the aromatase gene. On the other hand, there are no clear age-dependent changes in estrogen secretion. But, in men with disorders of glucose metabolism and also of increased body mass index, the serum estrogen concentrations are significantly elevated. There are also strong positive correlations between serum estrogen levels and bone density, including prevalence of fractures and mood in men. New fields of interest are natural fatty esters of endogenous estrogens, e.g. lipoprotein-associated estrogens, and the role and clinical significance of tissue-specific, local estrogen biosynthesis (e.g. different promoters of the aromatase gene). Exogenous estrogen treatment is focused today on patients with normal testosterone and low levels of circulating estrogens documented on several occasions and with clinical symptoms of hormone deficiency; male-to-female transsexuals; and selected patients with prostate cancer. Some clinical studies show the benefits of estrogen treatment on some cardiovascular parameters and for treating selected signs of mental stress. An indirect estrogen replacement can occur if dehydroepiandrosterone is given orally to men. The clinical usefulness of dissociated estrogens, including non-feminizing estrogens and selective estrogen receptor modulators, is still an open question. The beneficial action of phytoestrogens in lowering the clinical symptoms of benign prostatic hyperplasia is well documented. Finally, the question about the definitive influence of so-called endocrine disruptors (xenoestrogens) on sexual functions in men is also discussed.     

Gambling Type,Substance Abuse,Health and Psychosocial Correlates of Male and Female Problem Gamblers in a Nationally Representative French Sample

Many studies carried out on treatment-seeking problem gamblers (PG) have reported high levels of comorbid substance use disorders, and mental and physical health problems. Nevertheless, general population studies are still sparse, most of them have been carried out in the United States or Canada, and gender differences have not always been considered. Thus, the aim of this study was to describe the type of games, and psychological and physical correlates in male and female PG in a nationally representative French sample. The total sample studied involved 25,647 subjects aged 15–85 years, including 333 PG and 25,314 non-problem gamblers (NPG). Data were extracted from a large survey of a representative sample of the French general population. They were evaluated for sociodemographic variables, gambling behavior, type of gambling activity, substance use, psychological distress, body mass index, chronic disease, and lack of sleep. Overall, there were significant differences between PG and NPG in gender, age, education, employment and marital status, substance use disorders (alcohol, tobacco, cannabis, cocaine and heroin), psychological distress, obesity, lack of sleep and type of gambling activity. Although male and female PG had different profiles, the gambling type, especially strategic games, appeared as an important variable in the relationship between gender and problem gambling. This research underlines the importance of considering gender differences and gambling type in the study of gambling disorders. Identifying specific factors in the relationship between gender, gambling type and gambling problems may help improve clinical interventions and health promotion strategies.     

Comparison of Temperament and Character Between Early- and Late-Onset Korean Male Pathological Gamblers

Purposes  

We investigated differences in temperament and character between early and late onset Korean pathological gamblers to identify whether the age of onset of pathological gambling (PG) could discriminate PG subtypes, like in alcoholism.     

Forms of gambling,gambling involvement and problem gambling: evidence from a Swedish population survey

The purpose of this study was to explore the association between problem gambling (PG) and participation in different forms of gambling in order to elucidate relationships between PG, gambling involvement and gambling intensity. Using data from the first wave of the Swedish Longitudinal Gambling Study (Swelogs) (n = 4,991), the study tested four hypotheses, namely that (1) some forms of gambling are more closely associated with PG than other forms; (2) high gambling involvement is associated with PG; (3) gambling involvement is positively associated with the intensity of gambling; and (4) the relationship between gambling involvement and PG is influenced by the specific forms of gambling in which individuals participate. All four hypotheses were supported. More specifically, the study found that while many PGs regularly participate in multiple forms of gambling, half of PGs participate regularly in only one or two forms of gambling. The study concluded that some forms of gambling are more closely associated with problem gambling than other forms, and that gambling policy and regulation, as well as the development of responsible gambling initiatives, should focus on these forms.     

A Preliminary Study of the Neural Correlates of the Intensities of Self-Reported Gambling Urges and Emotions in Men with Pathological Gambling

Although self-reported gambling urge intensities have clinical utility in the treatment of pathological gambling (PG), prior studies have not investigated their neural correlates. Functional magnetic resonance imaging (fMRI) was conducted while 10 men with PG and 11 control comparison (CON) men viewed videotaped scenarios of gambling, happy or sad content. Participants rated the intensity of their emotions and motivations and reported the qualities of their responses. Relative to the CON group, the PG group reported similar responses to sad and happy scenarios, but stronger emotional responses and gambling urges when viewing the gambling scenarios. Correlations between self-reported responses and brain activations were typically strongest during the period of reported onset of emotional/motivational response and more robust in PG than in CON subjects for all conditions. During this epoch, corresponding with conscious awareness of an emotional/motivational response, subjective ratings of gambling urges in the PG group were negatively correlated with medial prefrontal cortex activation and positively correlated with middle temporal gyrus and temporal pole activations. Sadness ratings in the PG group correlated positively with activation of the medial orbitofrontal cortex, middle temporal gyrus, and retrosplenial cortex, while self-reported happiness during the happy videos demonstrated largely inverse correlations with activations in the temporal poles. Brain areas identified in the PG subjects have been implicated in explicit, self-referential processing and episodic memory. The findings demonstrate different patterns of correlations between subjective measures of emotions and motivations in PG and CON subjects when viewing material of corresponding content, suggesting in PG alterations in the neural correlates underlying experiential aspects of affective processing.     

Problem gambling among female prisoners: lifetime prevalence,help-seeking behaviour and association with incarceration

The widespread introduction of electronic gaming machines (EGMs) in Australia has seen problem gambling (PG) rates soar over the past decade. This has been particularly apparent among women, with presentations to gambling help services increasing fivefold, and 90% of them indicating EGMs as the problem. Prisoners represent a group containing the highest PG rate found in any population. Despite a sharp increase in PG among women and the well-established link between offenders and PG, little data exists concerning PG among female prisoners. This study examined lifetime prevalence of PG among female prisoners in South Australia. The Early Intervention Gambling Health Test was administered to 74 female prisoners. Previous help-seeking behaviour and association with incarceration were also examined. Sixty-four percent of respondents indicated PG with one in six reporting they were incarcerated due to PG-related offending. Problem gamblers whose incarceration was related to PG were more likely to indicate they had gambled to try and win money to repay debts than problem gamblers incarcerated for unrelated offending. Given high levels of PG and overall low rates of help-seeking, women’s prisons may provide an opportunity to engage this high-risk population with effective treatment.     

Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the α-adrenergic receptor antagonist

Background: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment.

Methods: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment.

Results: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p?=?.01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p?=?.0388) and rs4646437 in CYP3A4 at 7q21.1 (p?=?.0325), associated with drug effect. (4) Allele “G” for rs16902947 was found to be risk alleles for BPH risk (OR=?2.357, 95%CI 1.01–1.48). The “A” allele of rs4646437 was associated with lower IPSS at baseline (β=??0.4232, p=?.03255).

Conclusions: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.     

Testosterone metabolism,dose–response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men

In this review selected toxicological problems related to testosterone therapy in hypogonadal men are discussed. Applying ‘classical’ pharmacological/toxicological findings (e.g. animal studies on short- and long-term toxicity) to clinical situations is not very helpful. Molecular biological knowledge and especially evaluation of epidemiological studies, as well as intervention studies, on testosterone therapy in hypogonadal men are more useful. Potential risks include overdosage for lifestyle reasons, e.g. excessive muscle building and reduction of visceral obesity, when erythrocytosis occurs concomitantly. Modern galenic formulations of testosterone administration (e.g. transdermal gel, suitable testosterone esters for intramuscular application and newer oral preparations) avoid supraphysiological serum concentrations, therefore significantly reducing the toxicological risk. A hypothetical model of the toxicological risks of testosterone therapy is given that is based on the influence of testosterone metabolism (aromatization vs. reduction) of the respective parameter/target chosen. Finally, the great influence of polymorphisms of the androgen receptor on the assessment of toxicological risk and on the individualization of androgen therapy is shown. Already existing national, continental and international guidelines or recommendations for the testosterone therapy should be harmonized.     

An Exploratory Study of Clinical Measures Associated with Subsyndromal Pathological Gambling in Patients with Binge Eating Disorder

Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.     

Gene - Environment Interplay, Family Relationships, and Child Adjustment

This paper reviews behavioral genetic research from the past decade that has moved beyond simply studying the independent influences of genes and environments. The studies considered in this review have instead focused on understanding gene - environment interplay, including genotype - environment correlation ( rGE) and genotype × environment interaction (G × E). Studies have suggested that rGE is an important pathway through which family relationships are associated with child adjustment. Also important are direct causal influences of family relationships on child adjustment, independent of genetic confounds. Other studies have indicated that genetic and environmental influences on child adjustment are moderated by different levels of family relationships in G × E interactions. Genetically informed studies that have examined family relations have been critical to advancing our understanding of gene - environment interplay.     

Behavioural Addictions in Adolescents and Young Adults: Results from a Prevalence Study

Our study aims to assess the prevalence of behavioural addictions in an adolescent population, evaluating the effects of gender and age, and to assess the correlations among different behavioural addictions. 2853 high school students were assessed in order to evaluate the prevalence of behavioural addictions such as Pathological Gambling (PG), Compulsive Buying (CB), Exercise Addiction (EA), Internet Addiction (IA), and Work Addiction (WA), in a population of Italian adolescents. The South Oaks Gambling Screen-Revised Adolescent (SOGS-RA), the Compulsive Buying Scale (CBS), the Exercise Addiction Inventory (EAI), the Internet Addiction Test (IAT), and the Work Addiction Risk Test (WART), were compiled anonymously by the students. Overall prevalence was 7.0% for PG, 11.3% for CB, 1.2% for IA, 7.6% for WA, 8.5% for EA. PG and EA were more common among boys, while gender had no effect on the other conditions. CB was more common among younger (<18 years old) students. The scores of all of these scales were significantly correlated. The strong correlation among different addictive behaviours is in line with the hypothesis of a common psychopathological dimension underlying these phenomena. Further studies are needed to assess personality traits and other clinical disorders associated with these problems behaviours.     

Social Environmental Variation, Plasticity Genes, and Aggression: Evidence for the Differential Susceptibility Hypothesis

Although G×E studies are typically based on the assumption that some individuals possess genetic variants that enhance their vulnerability to environmental adversity, the differential susceptibility perspective posits that these individuals are simply more susceptible to environmental influence than others. An important implication of this model is that those persons most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. The present study tested several implications of this proposition. Using longitudinal data from a sample of several hundred African Americans, we found that relatively common variants of the dopamine receptor gene and the serotonin transporter gene interact with social environmental conditions to predict aggression in a manner consonant with differential susceptibility. When the social environment was adverse, individuals with these genetic variants manifested more aggression than other genotypes, whereas when the environment was supportive they demonstrated less aggression than other genotypes. Further, we found that these genetic variants interact with environmental conditions to foster various cognitive schemas and emotions in a manner consistent with differential susceptibility and that a latent construct formed by these schemas and emotions mediated the effect of gene by environment interaction on aggression.