Axion Paradigm with Color-Mediated Neutrino Masses.

We propose a generalized Kim-Shifman-Vainshtein-Zakharov-type axion framework in which colored fermions and scalars act as two-loop Majorana neutrino-mass mediators. The global Peccei-Quinn symmetry under which exotic fermions are charged solves the strong CP problem. Within our general proposal, various setups can be distinguished by probing the axion-to-photon coupling at helioscopes and haloscopes. We also comment on axion dark-matter production in the early Universe.

Use of office based transnasal oesophagoscopy in management of Head & Neck conditions during the COVID-19 pandemic at the Royal Albert Edward Infirmary, Wigan, United Kingdom.

OBJECTIVES: To assess the clinical and cost effectiveness of transnasal oesophagoscopy (TNO) in cases of suspected upper aerodigestive tract malignancy and define its role as a safe alternative to panendoscopy. We have also analysed if the implementation of TNO during the COVID-19 pandemic was beneficial in order to provide uninterrupted care to the patients with the limited resources available in these challenging times. METHODS: All patients who underwent TNO guided biopsies or dilatation attempted over a 7 month period during COVID- 19 pandemic were included by searching the hospital and department database at The Royal Albert Edward Infirmary. A comparative group of patients who underwent panendoscopy over 9 months were included for comparison. Demographic data, histological diagnosis, second procedure and cost involved were recorded. RESULTS: During this period, 20 TNO procedures (16 biopsies and 4 dilatations) were attempted which were compared with 20 panendoscopy procedures. The diagnostic accuracy of TNO biopsy for identifying benign and malignant pathology was 81.1%. The sensitivity and specificity for identifying malignancy was 76.9% and 100% respectively. The most common lesion location was laryngeal (43.8%) followed by oropharyngeal (37.5%), more specifically located at the tongue base. The median waiting period between the procedure being listed and TNO being performed was 5.5 days compared to 12 days for panendoscopy. There were 12/16 patients who did not require further interventions for histological diagnosis of the tumor. The TNO procedure was well tolerated with no complications and all were done under local anaesthesia as outpatient procedure without need for admission. TNO resulted in cost saving of £356 per case on a standard NHS tariff. CONCLUSION: TNO is a valuable diagnostic tool for patients with suspected UADT malignancy and dysphagia and has proven to be an asset during the COVID-19 pandemic when we have to make the best use of the limited theatre time and resources. Also, the cost analysis showed that outpatient based TNO can provide significant cost savings for the current standard of care. Furthermore, it has shown better patient tolerability, lesser complications and shortened the time for diagnosis and hence starting timely treatment for these patients.

Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

[On the legalization debate of non-medical cannabis consumption : Position paper of the German Association for Psychiatry, Psychotherapy and Psychosomatics]. / Zur Legalisierungsdebatte des nichtmedizinischen Cannabiskonsums : DGPPN-Positionspapier.

Calls are increasing for the legalization of cannabis. Some legal experts, various politicians, political parties and associations are demanding a change in drug policy. The legalization debate is lively and receiving wide coverage in the media. The German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) comments on the most important questions from a medical scientific perspective: can cannabis consumption trigger mental illnesses, what consequences would legalization have for the healthcare system and where is more research needed?

[Barriers to Addressing Pregnant Patients' Cigarette and Alcohol Use: A Focus Group Study with Gynecologists]. / Barrieren in der Thematisierung des Tabak- und Alkoholkonsums Schwangerer in der gynäkologischen Praxis. Eine Fokusgruppenstudie mit Frauenärzten.

Objectives/Purpose: Alcohol drinking and tobacco smoking pose high health risks for the unborn child. Even though routine testing during the course of pregnancy facilitates early intervention, addressing substance use in pregnancy seems to be more difficult. The aim of the study was to identify barriers to addressing pregnant patients' cigarette and alcohol use. Methods: 2 focus groups (in total N=10 participants) were conducted with gynaecologists. The transcripts of the discussions were analysed using Mayring's approach of qualitative text analysis. Results: Avoidance of addressing substance abuse directly, the social and educational background of patients influencing the communication in this matter and the physicians' ambivalence about their limits of responsibility were barriers often mentioned by the participants. Conclusion: In view of the several structural and individual barriers among gynaecologists identified in this study, gynaecologists obviously cannot be the only health professionals taking responsibility for coping with substance abuse among pregnant women. Strategies should be designed, e. g., to standardise the identification, counselling and referral process. Physicians should receive more support in improving their competences, and effective low-threshold treatment programmes for the women affected are required.

[Methodology of the S3 guidelines on alcohol and tobacco-related disorders]. / Methodik der S3-Leitlinien für alkohol- und tabakbezogene Störungen.

BACKGROUND: From 2010 until 2015 two interdisciplinary evidence-based guidelines were developed to summarize the current knowledge regarding screening, diagnostics and treatment of alcohol and tobacco-related disorders. METHODS: Both guidelines were prepared under the auspices of the German Society for Psychiatry, Psychotherapy and Psychosomatics (Deutsche Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde, DGPPN) and the German Society for Addiction Research and Therapy (Deutsche Gesellschaft für Suchtforschung und -therapie, DG-Sucht). To meet the methodological criteria for the highest quality guidelines (S3 criteria) as defined by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) the following criteria were realized: (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. RESULTS: More than 60 clinical experts and researchers analyzed the scientific literature. In total 41 international and national guidelines (23 for alcohol and 18 for tobacco) were used. Moreover, 83 systematic Cochrane reviews (alcohol 28, tobacco 55) and 5863 articles (alcohol 2213, tobacco 3650) were analyzed. A total of 7 expert groups formulated 174 recommendations for the screening, diagnosis and treatment of alcohol-related disorders. Six expert groups created 81 recommendations for the screening, diagnosis and treatment of tobacco-related disorders. Approximately 50 scientific associations, professional organizations, patient and family initiatives, as well as representatives of the healthcare system formed a consensus group. In seven 1 and 2-day conferences, all clinical recommendations were discussed and approved by this group. Both guidelines will be revised on a regular basis to guarantee that the clinical recommendations are kept up to date. CONCLUSIONS: Both systematically developed, evidence-based treatment guidelines are comprehensive instruments to provide orientation and assist the decision-making process for physicians, psychologists and other therapists as well as patients and their families in the diagnosis and treatment of alcohol and tobacco use related disorders.

[Psychiatric comorbidities with tobacco-related disorders]. / Psychiatrische Komorbiditäten bei tabakbedingten Störungen.

The coincidence of tobacco smoking and psychiatric disorders is of great epidemiological and therapeutic importance. Tobacco smoking by people with mental disorders leads to disproportionately high somatic health risks, an adverse clinical course, poorer clinical outcomes and reduced quality of life (QoL). The etiological causes of the high comorbidity between smoking and mental disorders are still unclear: currently, tobacco smoking is discussed as being either the consequence or contributory cause of psychological disorders or both disorders share common antecedents and interactions. Psychiatric patients are motivated to quit and smoking cessation is not generally less effective with smokers with mental disorders than with mentally healthy individuals. Specific smoking cessation programs in the inpatient and outpatient settings are time-consuming and complex but effective. Within the framework of the current S3 guidelines the international evidence has been updated and transformed into treatment guidelines following an elaborate consensus process. Basically the same interventional measures should be used as with mentally healthy individuals; however, smokers with a psychological comorbidity often need more intensive adjuvant psychotherapeutic interventions and often need pharmaceutical support, (bupropion, varenicline and nicotine replacement therapy). Due to the overall unsatisfactory findings the treatment guidelines are partially based on clinical consensus decisions. In this field, a considerable need for research has been determined.

[Normative definition of staff requirement for a guideline-adherent inpatient qualified detoxification treatment in alcohol dependence]. / Personalbedarfsermittlung für eine leitliniengerechte stationäre Qualifizierte Entzugsbehandlung bei Alkoholabhängigkeit.

The central element of the "qualified withdrawal treatment" of alcohol dependence is - in addition to physical withdrawal treatment - psychotherapy. The treatment of the underlying addictive disorder that is displayed by intoxication, harmful behaviour and withdrawal symptoms is only possible with a combination of somatic and psychotherapeutic treatment elements. The successfully established multimodal therapy of the "qualified alcohol withdrawal treatment", postulated in the current S3-Treatment Guidelines, requires a multi-disciplinary treatment team with psychotherapeutic competence. The aim of the present work is to calculate the normative staff requirement of a guideline-based 21-day qualified withdrawal treatment and to compare the result with the staffing regulations of the German Institute for Hospital Reimbursement. The present data support the hypothesis that even in the case of a hundred per cent implementation of these data, adequate therapy of alcohol-related disorders, according to the guidelines, is not feasible. This has to be considered when further developing the finance compensation system based on the described superseded elements of the German Institute for Hospital Reimbursement.

[Guideline-oriented treatment of alcohol-related disorders]. / Leitlinienorientierte Behandlung alkoholbezogener Störungen.

Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15% of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved.This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40% could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year.

[Psychotherapy and pharmacotherapy for harmful tobacco use and tobacco dependency]. / Psycho- und Pharmakotherapie bei schädlichem Tabakgebrauch und -abhängigkeit.

Tobacco consumption is one of the major preventable health risk factors. In Germany approximately 110,000 people prematurely die from tobacco-related diseases and approximately 50% of regular smokers are considered to be tobacco dependent. Nevertheless, motivation to quit smoking is low and the long-term abstinence rates after attempts to stop smoking without professional support are far below 10%. As part of the S3 treatment guidelines 78 recommendations for motivation and early interventions for smokers unwilling to quit as well as psychotherapeutic and pharmacological support for smokers willing to quit were formulated after an systematic search of the current literature. More than 50 professional associations adopted the recommendations and background information in a complex certification process. In this article the scientific evidence base regarding the psychotherapeutic and pharmacological treatment options as well as recommendations and further information about indications and treatment implementation are presented. By following these guidelines for treatment of heavy smokers who are willing to quit combined with individual and group therapies on the basis of behavioral treatment strategies and pharmacological support, long-term success rates of almost 30% can be achieved.

Presenting phenotype of paediatric inflammatory bowel disease in Wessex, Southern England 2010-2013.

AIM: There has been at least a twofold increase in the incidence of paediatric inflammatory bowel disease (PIBD) over the last 20 years; we report the presenting features from 2010 to 2013 and compare with previous data. METHODS: All patients diagnosed with PIBD at University Hospitals Southampton from 2010 to 2013 were identified from an in-house database. Data were obtained from paper and electronic notes. Height, weight and BMI SDS are presented as median values (95% CI). RESULTS: One hundred and seventy-two patients were included (median age at diagnosis 13.5, 115 male); Crohn's disease (CD) - 107, UC - 50, inflammatory bowel disease unclassified (IBDU) - 15. The most common presenting features of CD were abdominal pain (86%), diarrhoea (78.5%) and weight loss (56.1%); 42.1% of patients had all three. In UC blood in stool (92%), diarrhoea (92%) and abdominal pain (88%) were the most common; all three in 76% of patients. CD presented with ileocolonic disease in 52.5%. UC presented with pancolitis in 64%. There was growth delay in CD: height -0.37 (-0.60 to -0.14); weight -1.09 (-1.35 to -0.83). Growth was maintained in UC: height 0.53 (0.19 to 0.87); weight 0.14 (-0.20 to 0.48). CONCLUSION: Paediatric inflammatory bowel disease phenotype remains as extensive despite increasing incidence. Although the classical phenotype is common, a reasonable proportion present with atypical features, normal growth and normal blood markers.

Bone loss in a new rodent model combining spinal cord injury and cast immobilization.

OBJECTIVES: Characterize bone loss in our newly developed severe contusion spinal cord injury (SCI) plus hindlimb immobilization (IMM) model and determine the influence of muscle contractility on skeletal integrity after SCI. METHODS: Female Sprague-Dawley rats were randomized to: (a) intact controls, (b) severe contusion SCI euthanized at Day 7 (SCI-7) or (c) Day 21 (SCI-21), (d) 14 days IMM-alone, (e) SCI+IMM, or (f) SCI+IMM plus 14 days body weight supported treadmill exercise (SCI+IMM+TM). RESULTS: SCI-7 and SCI-21 exhibited a >20% reduction in cancellous volumetric bone mineral density (vBMD) in the hindlimbs (p⋜0.01), characterized by reductions in cancellous bone volume (cBV/TV%), trabecular number (Tb.N), and trabecular thickness. IMM-alone induced no observable bone loss. SCI+IMM exacerbated cancellous vBMD deficits with values being >45% below Controls (p⋜0.01) resulting from reduced cBV/TV% and Tb.N. SCI+IMM also produced the greatest cortical bone loss with distal femoral cortical area and cortical thickness being 14-28% below Controls (p⋜0.01) and bone strength being 37% below Controls (p⋜0.01). SCI+IMM+TM partially alleviated bone deficits, but values remained below Controls. CONCLUSIONS: Residual and/or facilitated muscle contractility ameliorate bone decrements after severe SCI. Our novel SCI+IMM model represents a clinically-relevant means of assessing strategies to prevent SCI-induced skeletal deficits.

[Smoking cessation in patients with COPD]. / Tabakentwöhnung bei COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Cigarette smoking is the main cause of COPD. Quitting smoking is thus the most effective treatment strategy and central in COPD prevention. A number of guidelines on prevention, diagnosis, therapy and rehabilitation of COPD have been published. To help implementing and standardizing smoking cessation in COPD a guideline was published 2008 in Germany focusing on this complex issue. The present guideline is an update of the 2008 guideline and has a high grade of evidence (S3 according to the AWMF; Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften). The guideline gives comprehensive and practical information on how to integrate smoking cessation as an central part of COPD therapy.

Comparison of scar thickness measurements using trans-vaginal sonography and MRI in cases of pregnancy with previous caesarean section. Do they correlate with actual scar thickness?

The aim of this study was to evaluate scar thickness in cases of pregnancy with previous caesarean section, by trans-vaginal sonography (TVS) and magnetic resonance imaging (MRI), and to correlate precision of radiologically-measured scar thickness with actual measurement of scar thickness. A total of 35 pregnant patients with previous caesarean section planned for elective caesarean section, were evaluated prospectively. Their scar thickness was measured by TVS and MRI on the day of elective repeat caesarean section. These measurements were correlated with each other and with scar thickness measured during elective repeat caesarean section by using a caliper. The correlation coefficients between scar thickness measured by TVS and MRI with peroperative evaluation with a caliper, were +0.72 and +0.59, respectively. The study concluded that as MRI is a costlier modality and TVS has better correlation coefficient with actual scar thickness, TVS can be considered to be the better modality for antenatal scar thickness measurement.

[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.

[Substance use associated disorders: frequency in patients with schizophrenic and affective psychoses]. / Substanzbezogene Störungen: Häufigkeit bei Patienten mit schizophrenen oder affektiven Störungsbildern.

BACKGROUND: Alcohol and substance use disorders (ASUD) are considered to be among the most frequent comorbidities in schizophrenic and affective psychoses and have a significant negative influence on their course and prognosis. In the present study patients with diagnosis from the ICD-10 category F2 or F3 were examined regarding a substance use disorder in a multicentre cross-section evaluation at nine psychiatric hospitals in Baden-Württemberg. The aim of this study is to discuss the current research on substance use disorders and psychosis comorbidity regarding the theoretical models by means of collected data. METHODS: The examination of 50 consecutive admissions per centre is based on a shortened version of the European Severity Index (Europ ASI). An initial urine drug screening was carried out with all patients after admission. Statistical assessment was based on percentage distributions, mean values, standard deviations and suitable correlation analysis. RESULTS: The representative sample included 448 patients. A proportion of 169 patients (37.7%) had a dual diagnosis F2 and F1 and a proportion of 144 patients (32.1%) had a dual diagnosis F3 and F1; 64 patients (14.3%) had an F2 diagnosis and 71 patients (15.8%) had an F3 diagnosis without ASUD. Apart from lifetime use of alcohol (n = 268) and tobacco (n = 325) hypnotics/tranquilizers (n = 214), cannabis (n = 156), opioids (n = 71), stimulants (n = 96) and hallucinogens (n = 36) were consumed. The most frequent combination and long-term intake consisted of tobacco, alcohol, hypnotics/tranquilizer, cannabis and psychostimulants especially in men with schizophrenic disorders. Regarding motivation before first substance use general psychological adjustment disorders (51%), peer impact (42%) and unspecific affective symptoms were predominant. CONCLUSIONS: Altogether the present study clearly demonstrates that patients suffering from schizophrenia, affective disorders and ASUD have significantly higher rates of more severe substance use disorders in their psychosocial environment and more suicidal behaviour than patients without substance misuse. The high rate in the cross-sectional prevalence of tobacco, alcohol, cannabis and psychostimulant use calls for more effective drug prevention.

E-Health intervention for subthreshold depression: Reach and two-year effects of a randomized controlled trial.

BACKGROUND: There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression. METHODS: Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months. RESULTS: Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = -0.05 points; d = -0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15). LIMITATIONS: Self-report measures and lack of information on patients' mental health treatment. DISCUSSION: ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes.

[Prevention of burnout by stress management]. / Stressmanagement als Burn-out-Prophylaxe.

Burnout is a possible consequence of excessive demands, high levels of stress, or a consequence of lack of resources for coping with difficult tasks. Systematic stress management might be effective in reducing the risk for development of a burnout syndrome. Based on a literature search on available research papers and meta-analyses in Medline and Pubmed, current findings on the content and effectiveness of stress management programs are reported for different target groups. Stress management programs can be divided into programs focusing on primary, secondary, and tertiary prevention. In contrast to primary prevention programs, secondary and tertiary preventive programs focus on the specific needs of different target groups. Cognitive-behavioral programs have been shown to be the most effective interventions. A combination of psycho-educational treatment with follow-up or booster sessions increases the long-term outcome in the prevention of burn-out syndromes. Beside the duration of the program, focus on problems and sustainability of supply is important for the long-term effectiveness in secondary and tertiary prevention.

Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

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.