Psychiatric comorbidity in alcohol use disorders: results from the German S3 guidelines.

Alcohol use disorders (AUD) have a high comorbidity with mental disorders. Vice versa, alcohol consumption plays an important role in affective disorders, anxiety disorders, ADHD, schizophrenic psychosis, and other mental disorders. In developing the current interdisciplinary, evidence-based treatment guideline on screening, diagnostics, and treatment of AUD, available research on comorbid mental diseases in AUD has been compiled to generate recommendations for treatment. The guideline was prepared under the responsibility of the German Association for Psychiatry, Psychotherapy, and Psychosomatics (DGPPN) and the German Association for Addiction Research and Therapy (DG-Sucht). To meet the methodological criteria for the highest quality guidelines ("S3-criteria") as defined by the Association of Scientific Medical Societies in Germany (AWMF), the following criteria were employed: (1) a systematic search, selection, and appraisal of the international literature; (2) a structured process to reach consensus; and (3) inclusion of all relevant representatives of future guideline users. After assessing and grading the available literature, the expert groups generated several recommendations for the screening, diagnosis, and treatment of comorbid mental disorders. These recommendations were subdivided into psycho-, pharmaco-, and combination therapies. These are the first guidelines ever to make specific treatment recommendations for comorbid mental diseases in AUD. The recommendations extend to different treatment approaches including diagnostics and settings to present available effective and state-of-the-art treatment approaches to clinicians. Hitherto, many clinical constellations have not been addressed in research. Therefore, recommendations for future research are specified.

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.

[Mental comorbidities of alcohol-related disorders]. / Psychische Komorbiditäten bei alkoholbedingten Störungen.

BACKGROUND: Alcohol-related disorders have a high comorbidity with mental disorders and vice versa, alcohol consumption plays an important role in affective disorders and schizophrenic psychoses. In developing the current S3 guidelines evidence-based knowledge on the rate and significance of comorbid disorders in alcohol use disorders has been compiled to generate recommendations for treatment. METHODS: In preparation for the guidelines, previous international guidelines and a systematic literature search were taken into consideration. Recommendations for various and specific clinical situations were derived from these sources based on evidence grading. Evidence and recommendations were subdivided into psychotherapy, pharmacotherapy and combination therapy, each having differential efficacies in the treatment of psychiatric symptoms and alcohol consumption behavior. Furthermore, a separate treatment pathway was developed for a stepwise approach to affective disorders for both comorbidities. CONCLUSION: Appearing for the first time in guidelines are specific treatment recommendations for comorbid mental diseases in alcohol use disorders. These recommendations extend to different treatment approaches including diagnostics and settings, affording clinicians more pragmatic relevance.

Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate.

Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P=4.6 × 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P=0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P=0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.