Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients-a randomized rater-blinded trial.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). METHODS: The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study's main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. ETHICS AND DISSEMINATION: The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. TRIAL REGISTRATION: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

Effect of a 1-year short message service in detoxified alcohol-dependent patients: a multi-center, open-label randomized controlled trial.

BACKGROUND AND AIMS: Existing evidence suggests that text message interventions can help people to reduce their alcohol consumption. However, studies with alcohol-dependent patients are lacking. In this study a 1-year automatic mobile phone-based short messaging service (SMS) intervention on alcohol consumption in patients after alcohol detoxification in hospital was compared with treatment as usual. DESIGN: Multi-center, randomized, controlled, two parallel-group, observer-blinded trial. SETTING AND PARTICIPANTS: Primary and secondary care: four hospitals and community (1 million residents, 7600 km2 area in Germany). A total of 462 patients with alcohol dependence (ICD-10) were included during inpatient detoxification treatment. Patients were randomly assigned (1 : 1) to an SMS intervention and treatment as usual (SMS + TAU; n = 230; mean age: 45.4 years; 22.6% women) or TAU alone (n = 232 mean age: 44.5 years; 22.8% women). Planned, automated messages were sent to patients over 1 year to record assistance needs. A 'yes' or missing response triggered a telephone call from a hospital therapist. Outcome was assessed by an independent survey center. MEASUREMENTS: The primary end-point was a three-category alcohol consumption measure covering months 10-12 after discharge: abstinence, non-heavy drinking, heavy drinking [men > 60 g/day; women > 40 g/day equal to World Health Organization (WHO) criteria: high risk and very high risk, mean consumption]. Secondary end-points were number of abstinent days over 12 months and frequency of abstinence. RESULTS: The arms differed primarily in the heavy drinking category (intervention group 22.2%, TAU-only group 32.3%) in months 9-12. This is reflected by an odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.11-2.54, P = 0.015 for heavy drinking versus non-heavy drinking/abstinence. No difference between treatments was found with respect to any drinking versus abstinence (OR = 1.13). These results were confirmed by models adjusting for randomization strata. CONCLUSIONS: In Germany, a 12-month mobile phone short messaging service-based intervention enhanced the reduction in heavy drinking for 1 year in routine care among adults with alcohol dependence discharged from inpatient alcohol detoxification.

Evaluation of algorithm development approaches: Development of biomarker panels for early detection of colorectal lesions.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in the U.S. Early detection of CRC can substantially increase survival rates. Test compliance may be improved by offering a blood-based test option. METHODS: Endoscopy II trial specimens were tested for AFP, CA19-9, CEA, hs-CRP, CyFra 21-1, Ferritin, Galectin-3, and TIMP-1 levels. These biomarkers, as well as patient demographic information (e.g., age, gender), were included in algorithm development. Six statistical methods were utilized to develop algorithms that would discriminate cancer vs. noncancers. Statistical methods included logistic regression, adaptive index modeling, partial least-squares discriminant analysis, feature vector (weighted and unweighted), and random forest. The performance of these algorithms was compared against benchmark criteria established for stool-based tests. RESULTS: Using several statistical methods, the presence of CRC and high-risk adenomas was detected with an AUCs of at least 0.65-0.76, with a few of models approaching the stool-based tests benchmark performance. Further, common markers were utilized across the different statistical techniques, with model complexities ranging from 3 to 9 markers. CONCLUSIONS: Predictive models identified subjects with CRC and high-risk adenomas with the similar levels of statistical accuracy. Clinical performance differences were minimal across the statistical techniques, although the intuitive interpretations, model complexity, clinical adoption and implementation varied.

Feasibility and Acceptability of an Intervention Providing Computer-Generated Tailored Feedback to Target Alcohol Consumption and Depressive Symptoms in Proactively Recruited Health Care Patients and Reactively Recruited Media Volunteers: Results of a Pilot Study.

BACKGROUND: A pre-post pilot study was conducted to test the feasibility, acceptability, and potential effectiveness of a fully automatized computer-based intervention targeting hazardous drinking and depressiveness in proactively recruited health care patients (HCPs). To address the importance of the sample selection when testing interventions, HCPs were compared to media recruited volunteers (MVs). METHOD: In a multicenter screening program 2,773 HCPs were screened for hazardous drinking and depressive symptoms. MVs were recruited via media solicitation. Over a period of 6 months, study participants received 6 individualized counseling letters and weekly short messages. Pre-post data were analyzed for 30 participants (15 HCPs, 15 MVs). Intervention acceptability was assessed in post-intervention interviews conducted with 32 study participants. RESULTS: MVs showed higher problem severity and motivation to change than HCPs. Over the course of the intervention both subsamples reduced regular binge drinking (HCPs: p = 0.016; MVs: p = 0.031) and depressiveness (HCPs: p = 0.020; MVs: p < 0.001). MVs further reduced average daily alcohol consumption (p = 0.034). The intervention received positive ratings from both subsamples, the alcohol module was rated more favorably by MVs than by HCPs (p = 0.012). Subsamples further differed in terms of intervention usage (p = 0.013). CONCLUSION: The intervention was technically and logistically feasible, well accepted, and may have the potential to reduce hazardous drinking and depressive symptoms in different populations. Subsamples differed in terms of problem severity, motivation to change, intervention usage, pre-post changes, and attitudes toward the intervention, showing that intervention development should involve the intended target populations to avoid biased conclusions on intervention effectiveness and acceptability.

Validation of a novel model for the early detection of hepatocellular carcinoma.

BACKGROUND: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. METHODS: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. RESULTS: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. CONCLUSIONS: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

The inverse link between genetic risk for schizophrenia and migraine through NMDA (N-methyl-D-aspartate) receptor activation via D-serine.

Schizophrenia has a considerable genetic background. Epidemiological studies suggest an inverse clinical association between schizophrenia and migraine. However, it is unclear to what extent this inverse comorbidity can be explained by genetic mechanisms or by schizophrenia-related behavioral factors. For both disorders hypotheses of glutamate N-methyl-D-aspartate (NMDA) receptor dysfunction have been developed in the past. We hypothesized that both conditions share common genetic factors with inverse effects, primary in the glutamatergic system and genes involved in NMDA activation. Data from the population based Study of Health in Pomerania (N=3973) were used. Based on the results from the recent genome-wide association study for schizophrenia, we calculated polygenic scores (PRS) for subsets of SNPs with different p-value cutoffs and for biological sub-entities. These scores were tested for an association of distinct biological pathways with migraine. The PRS for schizophrenia was inversely associated with migraine in our sample. This association was exclusively based on the genome-wide hits and on single nucleotide polymorphisms near or within genes encoding proteins involved in glutamatergic neurotransmission. This association could be attributed to a single intronic variant rs4523957 in SRR encoding serine-racemase. Additional expression quantitative trait loci analyses of functional variants in SRR and gene-by-gene interaction analyses further supported the validity of this finding. SRR represents the rate limiting enzyme for the synthesis of D-serine, an important co-agonist of the NMDA receptor. According to our results, a decreased versus increased activation of NMDA receptors may play a role in the etiology of schizophrenia, as well as in migraine.

Type of gambling as an independent risk factor for suicidal events in pathological gamblers.

Individuals with pathological gambling have an increased risk for suicidal events. Additionally, the prevalence of comorbid psychiatric disorders is high among pathological gamblers. This study analyzes whether the type of gambling is associated with suicidal events in pathological gamblers independently from comorbidity. Participants were recruited in 4 different ways: via random telephone sample from the general population, via individual invitation for study participation in gambling locations, through various media and the distribution of a leaflet in various settings, and via inpatient treatment facilities for pathological gambling. The final sample included 442 participants with a lifetime diagnosis of pathological gambling. A standardized clinical interview was conducted. High financial losses were associated with suicidal events (odds ratio [OR] = 1.94, 95% 95% confidence interval [CI], [1.11, 3.37]), as were mood disorders (OR = 7.70, 95% CI, [4.44, 13.37]) and female gender (OR = 2.52, 95% CI, [1.20, 5.28]). Gambling on electronic gambling machines in gambling halls or bars was associated with increased odds of suicidal events (OR = 2.94, 95% CI, [1.38, 6.24]). Other types of gambling, such as casino games or betting on sports, or the number of DSM-IV criteria for pathological gambling were not associated independently with suicidal events. Our findings suggest that gambling on electronic gambling machines in gambling halls or bars is associated with suicidal events in pathological gamblers independently of comorbidity. This result shows that the type of gambling needs to be considered as a relevant factor in gambling research.

A pilot study on the feasibility and acceptability of a text message-based aftercare treatment programme among alcohol outpatients.

AIMS: To test the feasibility, acceptability and initial effectiveness of a text message-based aftercare treatment programme among alcohol outpatients. METHODS: Clients treated for alcohol use disorders from three Swiss outpatient alcohol treatment centres were invited by their counsellors to participate in a study testing an interactive aftercare programme employing the use of text messages and personal phone calls. Fifty study participants were randomly assigned to either the 6-month aftercare programme (n = 25) or treatment as usual (n = 25). The intervention consisted of (a) monitoring of self-selected drinking goals at regular intervals, (b) motivational text messages to stick to self-selected drinking goals and (c) proactive telephone calls from counsellors when participants neglected to stick to their drinking goals or expressed a need for support. Follow-up interviews were conducted 6 months after randomization. RESULTS: Throughout the programme, participants received a total of 421 text message prompts. Out of these, participants provided valid replies to 371 (88.1%) within 48 h. Out of the 25 participants in the intervention group, 11 (44.0%) sent at least one call-for-help reply. Based on complete case data, at risk alcohol use at follow-up was 41.7% in the control group and 28.6% in the intervention group (OR = 0.56, 95% CI = 0.16-1.95, P = 0.36). CONCLUSIONS: The interactive low-intensive aftercare programme was well accepted by the participants. Testing its efficacy within an adequately powered randomized controlled trial might be reasonable.

The "Pathological Gambling and Epidemiology" (PAGE) study program: design and fieldwork.

The German federal states initiated the "Pathological Gambling and Epidemiology" (PAGE) program to evaluate the public health relevance of pathological gambling. The aim of PAGE was to estimate the prevalence of pathological gambling and cover the heterogenic presentation in the population with respect to comorbid substance use and mental disorders, risk and protective factors, course aspects, treatment utilization, triggering and maintenance factors of remission, and biological markers. This paper describes the methodological details of the study and reports basic prevalence data. Two sampling frames (landline and mobile telephone numbers) were used to generate a random sample from the general population consisting of 15,023 individuals (ages 14 to 64) completing a telephone interview. Additionally, high-risk populations have been approached in gambling locations, via media announcements, outpatient addiction services, debt counselors, probation assistants, self-help groups and specialized inpatient treatment facilities. The assessment included two steps: (1) a diagnostic interview comprising the gambling section of the Composite International Diagnostic Interview (CIDI) for case finding; (2) an in-depth clinical interview with participants reporting gambling problems. The in-depth clinical interview was completed by 594 participants, who were recruited from the general or high-risk populations. The program provides a rich epidemiological database which is available as a scientific use file.

Suicidal events among pathological gamblers: the role of comorbidity of axis I and axis II disorders.

The risk for suicidal ideation and suicide attempts among pathological gamblers is high compared to the general population. Little is known about the interplay of Axis I and Axis II disorders, severity of gambling disorder, and suicidal ideation and suicide attempts. The study aims to address this linkage. The sampling design of the study "Pathological Gambling and Epidemiology" (PAGE) included four recruitment channels: general population, gambling locations, project telephone hotline, and in-patient treatment for pathological gambling. A total of 442 study participants with lifetime pathological gambling received a clinical interview. The multivariate analysis showed mood disorders (Relative Risk Ratio, RRR=5.14, 95%-Confidence Interval, CI=2.91-9.07), substance use disorders (RRR=1.73, CI=1.02-2.94), and early onset of gambling disorder (RRR=0.96, CI=0.93-0.99) to be associated with suicidal ideation. Suicidal attempts were associated with female sex (RRR=3.58, CI=1.56-8.19), mood disorders (RRR=11.92, CI=4.70-30.26), and Cluster B personality disorders (RRR=2.40, CI=1.13-5.10). Among study participants with suicide attempts, more had a Cluster B personality disorder than among participants with ideation solely (RRR=3.08, CI=1.48-6.40). Among this large mixed sample of pathological gamblers, high proportions of individuals with suicidal events, multi-morbidity on Axis I, and a strong linkage to Cluster B personality disorders were found.

Changes in the perception of alcohol-related stigma in Germany over the last two decades.

BACKGROUND: Alcohol dependence is a severely stigmatized disorder. Perceived stigma may deter help-seeking and is associated with higher co-morbidity and self-stigma in persons with alcohol dependence. We assess changes in the perception of alcohol-related stigma over 21 years in the general population. METHODS: Two representative population surveys using identical methodology were conducted in Germany in 1990 and 2011 (n=1022 and n=967), eliciting the perceived discrimination and devaluation of someone with a history of alcohol problems as measured with an adoption of Link's Perceived Discrimination and Devaluation Scale (aPDDS), and perceived negative stereotypes of an "alcoholic." RESULTS: Both on item level and using factor scores, attitudes changed significantly between 1990 and 2011. Perceived discrimination and devaluation of someone with a history of alcohol dependence decreased considerably by 0.44 standard deviations (SD). Perceived negative stereotypes related to unpredictability of an "alcoholic" increased slightly by 0.15 SD, while perceived stereotypes related to strangeness decreased (-0.23 SD). CONCLUSIONS: Our findings suggest that particularly the image of someone who has received treatment for alcohol dependence has improved in Germany. This parallels increasing acceptance of professional treatment for alcohol dependence among the general population over the last twenty years, and contrasts with overall unchanged negative attitudes toward persons who actually suffer from alcohol problems.

A surveillance tool using mobile phone short message service to reduce alcohol consumption among alcohol-dependent patients.

BACKGROUND: In public health settings, short message service (SMS) appears to be a promising low-cost modality for reducing alcohol consumption. Here, we test a simple interactive SMS-based helpline with detoxified alcohol-dependent patients to extend findings to curative settings. METHODS: This controlled, prospective, 2-group before-after block-assignment, open pilot study tested the feasibility and efficacy of an 8-week outpatient interactive mobile phone SMS intervention (n = 42) against treatment as usual (TAU; n = 38) after inpatient detoxification. Patients were asked whether they needed any help via an automatically generated text message twice a week. A therapist called the individual back when notified. Alcohol consumption was assessed using the telephone version of Form-90 4 and 8 weeks after discharge from inpatient detoxification. The primary end point was defined as attaining low-risk consumption (males ≤30 g or 3.75 units per drinking day (DDD); females ≤20 g or 2.5 units per DDD) 8 weeks after discharge. Missing data were replaced by multiple imputation. RESULTS: Among all messages sent, 20.5% were followed by a phone call. Feasibility and acceptability were good, as indicated by successful implementation of the SMS procedure and the rapid inclusion of patients. Adherence was satisfactory with 57.14% of the participants replying to at least 50% of the prompts. Patients reported a typical preadmission DDD of 281.25 ± 244.61 g. In the SMS group, 55.7% of 42 patients, and 40% of 38 patients in the TAU group, achieved low-risk consumption (risk diff: 0.16; 95% CI -0.06 to 0.37; p = 0.122). CONCLUSIONS: In detoxified alcohol-dependent patients, relapse prevention based on SMS was well received and implemented efficiently and rapidly. An adequately powered multicenter study is currently being conducted to test the nonsignificant but encouraging findings of this exploratory study with more rigorous trial methods (ISRCTN78350716).

Associations between the oxytocin receptor gene (OXTR) and "mind-reading" in humans--an exploratory study.

BACKGROUND/AIMS: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. METHODS: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). RESULTS: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). CONCLUSION: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.

Size selection and adaptive evolution in an artificial chemistry.

A simple artificial chemistry for the Squirm3 artificial environment, consisting of replicators that produce quasi-universal enzymes, is presented. The aim of this system is twofold: first, to demonstrate the survival of extracellular replicators despite the presence of faster-replicating parasites; second, to observe the evolution of adaptively useful enzymes. Accomplishing these goals will underpin future attempts to attain open-ended and/or creative evolution in the Squirm3 environment. The first aim is achieved by attaching enzymes to their replicators. Our software implementation demonstrates replicators with 10 bases prospering in the presence of parasites with zero bases. To accomplish the second aim, a process for creating selection pressure toward longer molecules is introduced. The evolution and subsequent dominance of a replicator that produces an adaptively useful enzyme is demonstrated experimentally. Finally, we comment on the crucial role played by neutral evolution and discuss the biological significance of our results.

[Steroid use in free time bodybuilders]. / Steroidgebrauch bei Freizeit-Bodybuildern.

A sample of 74 male bodybuilders was analyzed for relationships between steroid abuse (abuse n=31; no abuse n=43) and self-esteem (Multidimensionale Selbstwertskala MSWS), body-image (Body-Image Questionnaire FK-ASA) as well as teasing (Physical Appearance Related Teasing Scale PARTS). In a logistic regression analysis age (p=0.001), low values for body expression (p=0.036) and high self-esteem (p=0.024) predicted steroid intake; training frequency or teasing experiences showed no effect. Contrary to earlier findings high and not low self-esteem was associated with steroid abuse. Because of the overlap between constructs narcissism and self-esteem further studies should disentangle the role of narcissism and self-esteem for steroid abuse in bodybuilders.

The stigma of alcohol dependence compared with other mental disorders: a review of population studies.

AIMS: Stigma is likely to aggravate the severe medical and social consequences of alcohol dependence. We aim to explore the characteristics of the alcohol dependence stigma by comparing it with the stigma of other conditions. METHODS: On the basis of a systematic literature search, we identified 17 representative population studies published before July 2010 that examine aspects of the stigma of alcoholism and simultaneously of other mental, medical or social conditions. Seven surveys were located in Europe, five in North America, three in New Zealand and one each in Brazil and Ethiopia, respectively. RESULTS: Compared with people suffering from other, substance-unrelated mental disorders, alcohol-dependent persons are less frequently regarded as mentally ill, are held much more responsible for their condition, provoke more social rejection and more negative emotions, and they are at particular risk for structural discrimination. Only with regard to being a danger, they are perceived to be at a similarly negative level to that of people suffering from schizophrenia. CONCLUSION: Alcoholism is a particularly severely stigmatized mental disorder. Cultural differences are likely, but under-researched. We discuss possible reasons for the differences between the stigma of alcoholism and of other mental diseases and the consequences for targeted anti-stigma initiatives.

Self-stigma in alcohol dependence: consequences for drinking-refusal self-efficacy.

BACKGROUND: Public stigma and self-stigma are two facets of mental illness stigma. Self-stigma denotes the internalization of negative public perceptions by persons with mental illness and has been shown to decrease general self-efficacy. To date, self-stigma has not been examined in people suffering from alcohol dependence, a particularly severely stigmatized mental disorder. METHODS: By adopting the Self-Stigma in Mental Illness Scale (SSMI), we developed the Self-Stigma in Alcohol Dependence Scale (SSAD). The scale is based on a focus-group derived list of 16 negative stereotypes about alcohol dependent persons. It consists of four 16-item subscales measuring four hypothetical stages of self-stigma, stereotype awareness (aware), stereotype agreement (agree), self-concurrence (apply), and self-esteem decrement (harm). We employed the SSAD in a cross-sectional study of 153 patients hospitalized for alcohol detoxification to examine its reliability and validity. RESULTS: The four stages of self-stigma could be reliably measured with the SSAD (Cronbach's alpha, 0.86-0.93). Each step in the process of self-stigmatization was most closely associated with its preceding step. Other significantly related independent variables in multiple regression analyses included desire for social distance (associated with agree), duration of drinking problems (associated with apply) and depressive symptoms (associated with apply and harm). Both apply and harm were significantly related to reduced drinking-refusal self-efficacy in analyses controlling for depressive symptoms and variables related to duration and severity of the drinking problem. DISCUSSION: The SSAD showed good validity and reliability measuring the stages of self-stigma in this group. Self-stigma appears to be associated with lower drinking-refusal self-efficacy.

Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population.

Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin-releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT-haplotype of the CRH-Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-2). The CRHR1-SNPs were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT-haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching "gene-wide" significance. Although we did not replicate the specific interaction of abuse and the TAT-haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI-2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene-environment interaction findings. © 2010 Wiley-Liss, Inc.

[Public attitudes towards alcohol dependence]. / Einstellung der Bevölkerung zu Alkoholkranken.

OBJECTIVE: Although among the most prevalent psychiatric conditions, alcoholism seems to be neglected within the current debate on mental illness stigma. We establish the state of current research on public attitudes towards alcohol dependent people. METHODS: In an extensive search of the literature, we identified 49 population studies on this topic between 1948 and 2008. 27 studies contained relevant information from Western countries and were included in this review. RESULTS: Although most people regard alcoholism as an illness, there is a strong tendency to blame those affected for their condition. Psycho-social causal attributions prevail over biologic explanations. Most people regard alcohol dependent persons as unpredictable and dangerous. The desire for social distance is stronger towards alcohol dependent persons than towards those with other psychiatric diagnoses such as depression or schizophrenia; only those addicted to illegal drugs suffer stronger rejection. Preferences of the public for resource allocation within the health care system put alcohol dependent patients at a potential disadvantage. CONCLUSIONS: Alcoholism is a severely stigmatized condition. In order to change the stigma of alcoholism, studies exploring theoretical models and mechanisms of stigmatization seem necessary.