Comorbidity, family history and personality traits in pathological gamblers compared with healthy controls.

BACKGROUND: While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. METHODS: In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. RESULTS: Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of sensation seeking. CONCLUSIONS: Our findings support classifying pathological gambling as a behavioural addiction in the ICD-11. This decision will have a significant impact on the approaches available for prevention (e.g. age limits) and treatment.

Genome-wide association study of pathological gambling.

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.

A comparison of region-of-interest measures for extracting whole brain data using survival analysis in alcoholism as an example.

BACKGROUND: Aggregation of functional magnetic resonance imaging (fMRI) data in regions-of-interest (ROIs) is required for complex statistical analyses not implemented in standard fMRI software. Different data-aggregation measures assess various aspects of neural activation, including spatial extent and intensity. NEW METHOD: In this study, conducted within the framework of the PREDICT study, we compared different aggregation measures for voxel-wise fMRI activations to be used as prognostic factors for relapse in 49 abstinent alcohol-dependent individuals in an outpatient setting using a cue-reactivity task. We compared the importance of the data-aggregation measures as prognostic factors for treatment outcomes by calculating the proportion of explained variation. RESULTS AND COMPARISON WITH EXISTING METHOD(S): Relapse risk was associated with cue-induced brain activation during abstinence in the ventral striatum (VS) and in the orbitofrontal cortex (OFC). While various ROI measures proved appropriate for using fMRI cue-reactivity to predict relapse, on the descriptive level the most "important" prognostic factor was a measure defined as the sum of t-values exceeding an individually defined threshold. Data collected in the VS was superior to that from other regions. CONCLUSIONS: In conclusion, it seems that fMRI cue-reactivity, especially in the VS, can be used as prognostic factor for relapse in abstinent alcohol-dependent patients. Our findings suggest that data-aggregation measures that take both spatial extent and intensity of cue-induced brain activation into account make better biomarkers for predicting relapse than measures that consider an activation's spatial extent or intensity alone.

[Computer games and Internet addiction as well as pathological gambling. Therapy approaches]. / Computerspiel- und Internetsucht und pathologisches Glücksspiel. Therapieansätze.

In accordance with the development of substance-related disorders, behavioral addictions, such as internet use disorder and pathological gambling are regarded as repetitive excessive behavior which increasingly turns into an automatic action which is difficult to control intentionally. This automatic behavior is reinforced by learning processes, associated with neuroadaption, especially in the dopaminergic reward system. Treatment aims at finding alternatives for gambling or online activities and reducing times online so that social contacts need to be re-established. The following article provides a short overview on studies assessing the effects of different psychotherapeutic and pharmacological interventions and details psychotherapeutic treatment options.

Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate.

In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.

[Gambling and internet addiction: review and research agenda]. / Glücksspiel- und Internetsucht: Review und Forschungsagenda.

Behavioral addictions, especially pathological gambling and internet addiction, have become a growing concern in research and health policy. Similarities between behavioral addictions and substance dependency are currently being discussed in the scientific community. Unfortunately the number of scientific studies on pathological gambling and internet addiction is still very low. The estimated prevalence of pathological gambling among the German population is 0.2-0.5%. These numbers are comparable to prevalence rates reported for illegal drug dependency. About 1.5 million people, i.e. 3% of the German population, are believed to be at risk of internet addiction. Therefore, it is important to investigate in more detail the clinical and neuroscientific basis of pathological gambling and internet addiction. In this review we summarize the current status of research regarding pathological gambling and internet addiction and outline possible future research perspectives in the field of neuroimaging and genetics. The aim is to develop a multifactorial and explanatory model which helps to improve the quality of existing therapeutic approaches and prevention strategies. At present, parts of the research are funded by the federal states. The authors of this article, supported by scientific associations, have established a research platform called 'pathological gambling' in which research methods and strategies will be discussed which facilitate the implementation of different studies on pathological gambling.