Masculine depression and its problem behaviors: use alcohol and drugs, work hard, and avoid psychiatry!

The gender role influences vulnerability to mental illness. Substance use, even critical in scale, is perceived as masculine, just like hard (over-)work, while not seeking help. With the ongoing separation between gender and sex, masculine norms become more relevant also to females' mental health. The male depression concept highlights the role of male symptoms in affective disorders. However, the empirical evidence is still limited. Here, we use the denomination 'masculine depression' to open the category for female patients and tested substance use patterns, health services' utilization, and working hours as predictors in a case-control study of 163 depressed in-patients (44% women; masculine vs. non-masculine depression according to a median split of the Male Depression Rating Scale-22) and 176 controls (51% women). We assessed higher depression severity in patients with masculine (vs. non-masculine) depression. Masculine depression (vs. non-masculine depression and vs. no depression) was predicted by more frequent and critical use of alcohol (including binge drinking), tobacco, and illicit drugs, and by longer working times. Moreover, fewer health services contacts due to mental complaints during the previous year were associated with masculine (vs. non-masculine) depression. Alarmingly, even critical substance misuse was not significantly associated with more frequent health services contacts; however, the higher the depression severity, the more contacts the patients reported. Here, we provide evidence that patients with masculine depression are highly burdened and undertreated, which applies equally to female and male patients. This study identified promising targets to establish specialized care offers.

Psychometric properties of the German Penn Alcohol Craving Scale.

Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores 'difficulty to resist' (items 4 and 5) and 'thoughts about alcohol' (items 1, 2, and 3) have an internal consistency (Cronbach's alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck's Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution ('difficulty to resist' and 'thoughts about alcohol') underlying the PACS-G version.

Meta-analytic evidence for a sex-diverging association between alcohol use and body mass index.

Alcohol use is an important health issue and has been suggested to contribute to the burden produced by obesity. Both alcohol use and obesity are subject to sex differences. The available studies on the relationship between alcohol use and body mass index (BMI) report inconsistent results with positive, negative, and null findings which requests a meta-analytic approach. Therefore, we conducted a meta-analysis of case-control, cohort, and cross-sectional studies. The systematic literature search and data extraction was performed by 3 independent raters. We conducted sex-separated meta-analyses and -regressions to investigate how alcohol consumption associates with BMI. Our systematic literature search resulted in 36 studies with 48 data sets (Nmen = 172,254; kmen = 30; Nwomen = 24,164; kwomen = 18; Nunknown sex = 672,344; kunknown sex = 24). Alcohol use was associated with higher BMI in men (g = 0.08 [0.07; 0.09]) and lower BMI in women (g = - 0.26 [- 0.29; - 0.22]). Moreover, we found the amount of daily alcohol intake in men (ß = 0.001 [0.0008; 0.0014]) and ethnicity in women (g[Caucasians] = - 0.45 versus g[Asians] = - 0.05; z = 11.5, p < 0.0001) to moderate these effects. We here identified sex-diverging relationships between alcohol use and BMI, found daily alcohol intake and ethnicity to sex-specifically moderate these effects, and argue that sex-specific choice of beverage type and higher amount of daily alcohol use in men than in women account for these observations. Future research is needed to provide empirical evidence for the underlying mechanisms.

Elevated Oxytocin Receptor Blood Concentrations Predict Higher Risk for, More, and Earlier 24-Month Hospital Readmissions after In-Patient Detoxification in Males with Alcohol Use Disorder.

Alcohol use disorder (AUD) is a major global mental health challenge. Knowledge concerning mechanisms underlying AUD and predictive biomarkers of AUD progression and relapse are insufficient. Recently, addiction research is focusing attention on the oxytocin system. However, to our knowledge, blood concentrations of the oxytocin receptor (OXTR) have not yet been studied in AUD. Here, in sex-separated analyses, OXTR serum concentrations were compared between early-abstinent in-patients with AUD (113 men, 87 women) and age-matched healthy controls (133 men, 107 women). The OXTR concentrations were correlated with sex hormone and oxytocin concentrations and alcohol-related hospital readmissions during a 24-month follow-up. In male patients with AUD, higher OXTR concentrations were found in those with an alcohol-related readmission than in those without (143%; p = 0.004), and they correlated with more prospective readmissions (ρ = 0.249; p = 0.008) and fewer days to the first readmission (ρ = -0.268; p = 0.004). In men and women, OXTR concentrations did not significantly differ between patients with AUD and controls. We found lower OXTR concentrations in smokers versus non-smokers in female patients (61%; p = 0.001) and controls (51%; p = 0.003). In controls, OXTR concentrations correlated with dihydrotestosterone (men, ρ = 0.189; p = 0.030) and testosterone concentrations (women, ρ = 0.281; p = 0.003). This clinical study provides novel insight into the role of serum OXTR levels in AUD. Future studies are encouraged to add to the available knowledge and investigate clinical implications of OXTR blood concentrations.

Bioimpedance Body Measures and Serum Lipid Levels in Masculine Depression.

Background: Major depressive disorder (MDD) is a main reason for suicide, and serum lipids are involved in both affective disorders and related suicidal behavior. Moreover, masculine depression has been suggested as a subtype of depression with an increased risk for suicide. Here, we studied the relationship between body measures, serum lipids, suicidal thoughts, and masculine depression. Methods: Depressed patients (44% women) were divided by a sex-separated median-split into a group of 81 "patients with masculine depression" (mean age ± standard error: 36.4 ± 1.6 years) and a group of 82 "patients with non-masculine depression" (age 45.7 ± 1.6 years) according to the Male Depression Risk Scale. We compared body measures, serum lipid levels, and past suicidal ideation between these groups and explored differences between these groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years). Results: Patients with masculine depression did not significantly differ from patients with non-masculine depression in any of the body measures, lipid markers, or suicidal thoughts. Compared to healthy controls, both patient groups showed significantly higher body fat (B[masculine depression] = 0.041 and B[non-masculine depression] = 0.050), lower high-density lipoprotein (HDL) cholesterol (B = -0.045 and -0.044), and a higher risk for suicidal thoughts (B = 3.927 and 2.663) than healthy controls. Suicidal thoughts were significantly associated with lower low-density lipoprotein (LDL)/HDL ratios (B = -0.455) in patients with depression and with higher LDL cholesterol levels (B = 0.020) in healthy controls subjects. Limitation: Correlational study design and focus on in-patients. Conclusion: In the studied cohort, masculine depression was not significantly associated with the analyzed parameters of body measures, serum lipids, or suicidal thoughts in in-patients with depression.

Sulphated dehydroepiandrosterone serum levels are reduced in women with alcohol use disorder and correlate negatively with craving: A sex-separated cross-sectional and longitudinal study.

Previous studies have established a role of sex hormones in alcohol use disorder (AUD).Only few clinical investigations with low numbers of patients with AUD have focused on the sulphated form of dehydroepiandrosterone (DHEA-S), despite its function as a neuromodulating sex steroid on receptors in the central nervous system (γ-aminobutyric acid type A, N-methyl-D-aspartate, sigma-1 receptors). DHEA-S serum levels were compared between 200 inpatients with AUD (44% women) admitted for withdrawal treatment and 240 healthy controls (45% women) and analysed longitudinally in patients from early abstinence (baseline) to a median of 5 days later. We also correlated DHEA-S levels with craving, liver enzyme activities, and prospective alcohol-related readmissions during a 24-month follow-up. DHEA-S concentrations were lower in female patients than in female healthy controls during baseline (70%) and decreased from baseline to follow-up in the female and male patients groups (down to: women, 92%; men, 76%). Baseline DHEA-S concentrations correlated with the total and obsessive subscales of the Obsessive-Compulsive Drinking Scale and with maximum visual analogue scale craving scores in female patients (Rho ≤ -0.240) and gamma-glutamyl transferase activity in female (Rho = -0.292) and male (Rho = -0.391) patients. DHEA-S did not significantly predict outcome. We found interactions with smoking behaviour and age. This is the first study based on large cohorts of inpatients with AUD undergoing a qualified detoxification treatment to provide sex-separated evidence for associations of DHEA-S serum concentrations with AUD and related phenotypes. The results stimulate further investigations whether DHEA-S directly influences alcohol craving building a basis to develop sex-sensitive prevention and treatment strategies.

Male depression syndrome is characterized by pronounced Cluster B personality traits.

BACKGROUND: Male depression syndrome (Male-DS) refers to alternative depression symptoms related to the male sex, such as externalizing behaviors, emotional suppression, substance misuse, and risk-seeking. Although these symptoms contribute to gender bias in the diagnosis of depression, Male-DS can be found in both sexes. In this cross-sectional study, we analyzed associations between Male-DS and clinical personality accentuations. METHODS: We compared clinical personality accentuations between 78 depressed patients with high Male-DS scores (46% women; mean age ± standard error of the mean: 36.5 ± 1.6 years) and 76 depressed patients with low Male-DS scores (43% women; age 44.8 ± 1.7 years). We also explored differences between the two patient groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years). RESULTS: Depressed patients with high Male-DS scores showed stronger borderline (partial η2 0.121), impulsive (0.112), and antisocial (0.078) personality accentuations than those with low Male-DS scores after Bonferroni adjustment and controlling for sex, depression severity, and age. Relative to healthy controls, patients with high Male-DS values scored higher in all personality dimensions except for the narcissistic dimension. Patients with low Male-DS values scored higher in all Cluster A and C dimensions and the impulsive and borderline dimensions, but their scores were lower in the narcissistic dimension. LIMITATIONS: Cross-sectional design and focus on in-patients. CONCLUSIONS: We found pronounced Cluster B personality in patients with high Male-DS scores versus patients with low scores. Further prospective research is needed to verify that Cluster B personality traits represent a pre-morbid risk factor for Male-DS.

Oxytocin blood concentrations in alcohol use disorder: A cross-sectional, longitudinal, and sex-separated study.

Alcohol use disorder (AUD) is a severe illness, for which we lack sufficient mechanistic understanding. Preliminary evidence associates AUD with the oxytocin (OXT) system. Here we investigated alterations in endogenous OXT blood concentrations in patients with AUD and their association with alcohol drinking and prospective course. In sex-separated analyses, OXT serum concentrations of 200 in-patients with AUD (56.5% male; baseline, 24-72 h of abstinence) were compared with those of 240 age-matched healthy controls (55.4% male), investigated longitudinally (follow-up, 5 days later), and tested for associations with alcohol drinking behavior and prospective 24-month alcohol-related hospital readmissions. At baseline, the patients showed increased OXT concentrations relative to controls (men, 156%, P < 0.001; women, 124%, P = 0.002). The elevations normalized at follow-up. In male patients, baseline OXT concentrations correlated positively with alcohol concentration at admission, the amount of alcohol consumption per drinking year, and the number of previous withdrawal treatments (Rho > 0.195, P < 0.044). In beverage type-specific analysis, baseline OXT concentrations correlated with liquor consumption positively in male and negatively in female patients (|Rho| > 0.277, P < 0.017). Higher baseline OXT concentrations predicted more readmissions and fewer days to the first readmission (|Rho| > 0.185, P < 0.050) in male patients. This study provides novel and sex-separated insights into the role of the OXT system in AUD. We identified a mechanism that might underlie the sex-separated choice of beverage type and established that increased OXT concentrations during early abstinence predict a worse outcome in male patients with AUD.

Body mass index and serum levels of soluble leptin receptor are sex-specifically related to alcohol binge drinking behavior.

OBJECTIVE: Binge drinking is a highly prevalent behavior in adolescents and young adults and a risk factor to develop alcohol use disorder. Body mass index (BMI) and blood levels of leptin peptide and its soluble receptor have been implicated in alcohol use disorder; however, their role in binge drinking remains to be investigated. METHOD: We studied associations of BMI, serum levels of soluble leptin receptor (ObRe) and leptin as well as the free leptin index with binge drinking in 93 male and 99 female young adults. RESULTS: In men, binge drinkers showed significantly higher BMI (kg/m2) than non-binge drinkers (23.67 vs. 22.08) and higher BMI correlated significantly with more severe binge drinking episodes (ρ = 0.251). In women, we found significantly higher ObRe (ng/ml) / BMI (kg/m2) values in binge drinkers than in non-binge drinkers (0.52 vs. 0.44) and ObRe/BMI values correlated significantly with more severe binge drinking episodes (ρ = 0.210). CONCLUSION: This study confirms that higher BMI associates with binge drinking in men and shows for the first time a role of ObRe/BMI in binge drinking in women. Our data emphasize the importance of further research in the field of metabolic markers and implications in neurobiological processes of binge drinking.

Progesterone serum levels correlate negatively with craving in female postmenopausal in-patients with alcohol use disorder: A sex- and menopausal status-separated study.

OBJECTIVE: Alcohol use disorder (AUD) shows a high prevalence and often takes a severe and chronic course. However, the underlying mechanisms still need to be better understood. There is increasing evidence for a role of sex hormones in AUD and for the importance of sex-separated concepts in addiction research. Nevertheless, only few data give insight into how progesterone is involved in AUD. METHOD: Serum progesterone levels were measured at baseline (during early abstinence) in 186 in-patients with AUD (19% premenopausal females, 20% postmenopausal females, 61% males) and at median 5 days later. They were compared with those of 233 healthy control subjects (24% premenopausal females, 19% postmenopausal females, 57% males). We quantified craving with the Obsessive Compulsive Drinking Scale (OCDS) and visual analogue scales (VAS). Alcohol-related hospital readmissions within a 24-month period following initial in-patient treatment were recorded. We conducted analyses separately for sex and for menopausal status in female participants. RESULTS: Postmenopausal females with AUD reported higher craving than premenopausal females. In postmenopausal females, higher baseline progesterone levels correlated with lower OCDS total craving and VAS craving, i.e., lower state craving and lower average, maximum, and less frequent craving during withdrawal. In males with AUD, progesterone levels at baseline tended to be higher than in controls and declined to follow-up. Alcohol-related readmissions were not significantly associated with serum progesterone levels. CONCLUSION: We provide first evidence that progesterone levels correlate with craving in females with AUD.

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study.

OBJECTIVE: Alcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically. METHOD: We measured and compared (median) serum lipids (triglycerides and total, HDL, and LDL cholesterol) and leptin activities (leptin, soluble leptin receptor [ObRe], and free leptin index) in 200 (males 56.5 %) early-abstinent alcohol-dependent in-patients and 240 (males 55.4 %) healthy controls and assessed alcohol-related readmissions during a 24 -month post-inclusion period. RESULTS: Male patients showed higher HDL cholesterol (61 versus 48 mg/dl), lower LDL/HDL ratios (2.06 versus 3.04), and lower free leptin index (0.30 versus 0.59) at study inclusion compared to healthy controls. In patients, ObRe levels were higher than in controls and decreased from inclusion to the second study-visit (at median 5 days later; males: 16.7-13.8 versus 11.0 ng/ml; females: 17.0-13.4 versus 12.1 ng/ml). The free leptin index increased between the two time points in females (0.80 versus 1.20). Lipids and leptin activities correlated with carbohydrate-deficient transferrin levels and liver enzyme activities. None of the serum parameters were significantly associated with alcohol-related readmissions. CONCLUSION: Our data support that serum lipid levels and leptin activities are involved in alcohol dependence. The parameters appear as possible indirect biomarkers for alcohol dependence.

Basic Human Body Dimensions Relate to Alcohol Dependence and Predict Hospital Readmission.

Alcohol dependence is a severe mental illness and there is a need for more effective preventive and therapeutic strategies. Translational research suggests that intrauterine sex hormone exposure modulates the risk and course of alcohol dependence during adulthood. During development, sex hormones permanently shape sexually dimorphic body dimensions. Thus, these dimensions may provide insight into sex hormone organization. Here, we compared body measurements (absolute, relative to, and residualized on height) between 200 alcohol-dependent in-patients and 240 age-matched healthy control subjects and investigated how these measurements associate with the patients' prospective 12- and 24-month outcome. The results show that alcohol dependence is related to lower absolute, relative, and residualized body measurements for height and weight, head circumference, bitragion head arc, lip-chin distance, hip, thigh, and calf circumference, and foot length and breadth. In male alcohol-dependent in-patients, higher risk, shorter latency, and more alcohol-related readmissions were predicted by higher absolute, relative, and residualized thigh and calf circumferences. The second-to-fourth finger length ratio, a putative proxy for prenatal sex hormone organization, was not convincingly correlated with the body dimensions, suggesting that the results represent pubertal (or later) effects. The study's findings have implications for further research. The body measurements' high accessibility may facilitate the future transition into clinical settings.

Crossed Eye/Hand Laterality and Left-Eyedness Predict a Positive 24-Month Outcome in Alcohol-Dependent Patients.

BACKGROUND: Available predictors of hospital readmission following withdrawal in alcohol-dependent patients are limited. However, such parameters are needed to optimize individualized treatment strategies. This study investigated whether crossed eye/hand laterality, eyedness, and handedness may predict outcomes in alcohol dependence. METHODS: The prospective study included 200 early-abstinent alcohol-dependent inpatients (n[males] = 113, n[females] = 87) and 240 control subjects (n[males] = 133, n[females] = 107). We assessed eyedness and handedness using the hole-in-the-card and Shimizu tests and documented alcohol-related readmissions over 12 and 24 months. RESULTS: Crossed eye/hand laterality and left-eyedness were associated with a reduced risk for alcohol-related readmission (12-month: odds ratios [OR] = 0.41, p = 0.008, OR = 0.42, p = 0.004; 24-month: OR = 0.57, p = 0.097, OR = 0.47, p = 0.016), fewer median readmissions (12-month: 0 vs. 1, p = 0.005, 0 vs. 1, p = 0.005; 24-month: 1 vs. 2, p = 0.014, 1 vs. 2, p = 0.006), and more mean days to the first readmission (12-month: 270 vs. 209, p = 0.007, 269 vs. 207, p = 0.003; 24-month: 462 vs. 335, p = 0.039, 461 vs. 323, p = 0.005). They also interacted with treatment and alcohol drinking history to predict the outcome. In sex-specific analyses, most of these effects remained significant in males but not in females. Handedness alone did not significantly predict outcome. Moreover, the laterality markers did not significantly differ between alcohol-dependent patients and control subjects. CONCLUSIONS: Determining crossed eye/hand laterality and eyedness may help to individualize relapse prevention in the future. Both are easily accessible predictors of alcohol-related readmission following inpatient withdrawal treatment.

Estrogen receptor 1 gene variants and estradiol activities in alcohol dependence.

OBJECTIVE: Alcohol use disorders inflict a great individual and societal burden. Although sex hormone effects have been implicated in alcohol dependence, research has mostly neglected estrogen activities and female alcohol-dependent patients. Here, we investigated associations of estrogen receptor 1 (ESR1) genetics and serum estradiol activities with aspects of alcohol dependence. METHOD: Serum estradiol activities of early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) were followed for at median 5 days and compared with healthy controls (n[♂] = 133, n[♀] = 107). All participants were genotyped for five ESR1 single nucleotide polymorphisms (rs6902771, rs11155819, rs6557171, rs2982683, rs2982712). RESULTS: Bioavailable estradiol levels decreased during withdrawal treatment (P[♂] < .001, P[♀] = .011). Male patients with an increase of bioavailable estradiol during withdrawal showed fewer days to (P = .033) and more alcohol-related readmissions (P < .05) during the 12-month follow-up. Higher estradiol and estradiol-to-testosterone activities were significantly related to liver, muscle, and cell count damage in male patients. Estradiol-to-testosterone activities in female patients were lower compared to female controls (total P = .013, bioavailable P = .009). Moreover, the ESR1 genotypes jointly separated alcohol-dependent patients from controls (P = .037). CONCLUSION: Our findings support the role of ESR1 genetics in alcohol dependence and show for the first time that estradiol activities may sex-specifically predict alcohol-related sequelae and outcome following in-patient withdrawal treatment.

Body mass index and craving predict 24-month hospital readmissions of alcohol-dependent in-patients following withdrawal.

OBJECTIVE: Addictive alcohol drinking, craving, and overeating share common etiopathological mechanisms. We investigated whether body mass index (BMI) and craving predict outcome of alcohol-dependent in-patients. METHOD: The prospective study included 101 male and 72 female early-abstinent alcohol-dependent in-patients. Craving was quantified by Obsessive-Compulsive Drinking Scale (OCDS) scores. We documented alcohol-related readmissions over 24 months. RESULTS: In males, a higher BMI was associated with alcohol-related hospital readmission (median 26.1 vs. 23.1 kg/m2, P = .007) and correlated with more (ρ = 0.286, P = .004) and earlier readmissions (ρ = -0.256, P = .010). These associations were stronger in the subgroup of active smokers (n = 79; median 25.9 vs. 22.3 kg/m2, P = .005; ρ = 0.350, P = .002; ρ = -0.340, P = .002). BMI did not significantly predict outcome in females. Males with at least one readmission reported higher OCDS scores than those without (OCDS-total, OCDS-obsessive, OCDS-compulsive, P < .040), and the OCDS scores correlated with more readmissions (males: OCDS-total, OCDS-obsessive, OCDS-compulsive, ρ > 0.244, P < .014; females: OCDS-compulsive, ρ = 0.341, P = .003) and fewer days to first readmission (males: OCDS-total, OCDS-compulsive, ρ < -0.195, P < .050; females: OCDS-compulsive, ρ = -0.335, P = .004). The OCDS scores explained 9 to 19% of the relationship between BMI and outcome in males. CONCLUSION: BMI and craving are easily accessible outcome predictors of alcohol-related readmission following in-patient withdrawal treatment. They might be used to individualize relapse prevention in the future.

Peripheral Acid Sphingomyelinase Activity Is Associated with Biomarkers and Phenotypes of Alcohol Use and Dependence in Patients and Healthy Controls.

By catalyzing the hydrolysis of sphingomyelin into ceramide, acid sphingomyelinase (ASM) changes the local composition of the plasma membrane with effects on receptor-mediated signaling. Altered enzyme activities have been noted in common human diseases, including alcohol dependence. However, the underlying mechanisms remain largely unresolved. Blood samples were collected from early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) and matched healthy controls (n[♂] = 133, n[♀] = 107), and analyzed for routine blood parameters and serum ASM activity. We confirmed increased secretory ASM activities in alcohol-dependent patients compared to healthy control subjects, which decreased slightly during detoxification. ASM activity correlated positively with blood alcohol concentration, withdrawal severity, biomarkers of alcohol dependence (liver enzyme activities of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase; homocysteine, carbohydrate-deficient transferrin; mean corpuscular volume, and creatine kinase). ASM activity correlated negatively with leukocyte and thrombocyte counts. ASM and gamma-glutamyl transferase were also associated in healthy subjects. Most effects were similar for males and females with different strengths. We describe previously unreported associations between ASM activity and markers of liver damage and myelosuppression. Further research should investigate whether this relationship is causal, or whether these parameters are part of a common pathway in order to gain insights into underlying mechanisms and develop clinical applications.

OPRM1 A118G and serum ß-endorphin interact with sex and digit ratio (2D:4D) to influence risk and course of alcohol dependence.

Activation of mesolimbic mu-opioid receptors by their endogenous ligand, ß-endorphin, can mediate the rewarding effects of alcohol. However, there is conflicting evidence on the relationship between the mu-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) and alcohol dependence risk. Preclinical evidence suggests that sex and sex hormone-dependent prenatal brain organization may interact with the opioid system to influence alcohol drinking behavior. We genotyped 200 alcohol-dependent patients and 240 healthy individuals for the OPRM1 A118G SNP and measured serum ß-endorphin level at recruitment and after acute withdrawal. We then determined the association between these factors and alcohol dependence risk and 24-month outcome in the context of both sex and second-to-fourth digit lengths ratio (2D:4D) - a biomarker of prenatal sex hormone levels. The OPRM1 A118G AA genotype associated with elevated risk of alcohol-related hospital readmission, more readmissions, and fewer days until first readmission in male patients only. After normalizing patient 2D:4D against control 2D:4D, we found that normalized 2D:4D ratios were lower in male 118G patients than male AA patients, suggesting prenatal androgens interact with OPRM1 to influence alcohol dependence risk. In addition, ß-endorphin levels after acute withdrawal correlated negatively with withdrawal severity in females but not in males, which may indicate ß-endorphin protects against withdrawal-induced stress in a sex-specific manner.

Religiosity, Guilt, Altruism and Forgiveness in Alcohol Dependence: Results of a Cross-sectional and Prospective Cohort Study.

AIMS: To compare religious denomination, religiosity, guilt, altruism and forgiveness between alcohol-dependent patients and healthy control subjects and to prospectively investigate their relationship to the disorder's 24-month course following in-patient withdrawal treatment. METHOD: This study in Franconia (a mainly Christian protestant region of southern Germany) applied six questionnaires to evaluate religiosity, guilt, altruism and forgiveness in 166 alcohol-dependent in-patients during withdrawal and compared findings with that of 240 healthy controls. RESULTS: Compared to controls religious denomination was more frequently reported by the patients (OR = 1.72, P = 0.014) and patients showed higher guilt (P < 0.001). The subjective attainability of altruism was lower in patients than in controls (P = 0.015). Higher scores on scale of inter-religious private practice predicted earlier (Rho = -0.184, P = 0.021) and more frequent alcohol-related readmissions during the follow-up (Rho = 0.207, P = 0.009). Higher religious affiliation was related to earlier (Rho = -0.214, P = 0.008) and more frequent alcohol-related readmissions (Rho = 0189, P = 0.020). Lower values of subjective attainability of altruism predicted a worse outcome (earlier [Rho = 0.231, P = 0.003] and more frequent readmissions [Rho = -0.223, P = 0.004]). The sex-specific analyses show that some of the associations are stronger in women and others are stronger in men; however, these gender differences are small and possibly biased by multiple hypothesis testing. CONCLUSIONS: We identified religious denomination, private religious practice, religious affiliation, guilt and reduced attainability of altruism as risk factors for alcohol dependence and a worse follow-up outcome. Our findings may help to establish future preventive and therapeutic strategies.

Cloninger Type 2 Score and Lesch Typology Predict Hospital Readmission of Female and Male Alcohol-Dependent Inpatients During a 24-Month Follow-Up.

BACKGROUND: Relapse after detoxification treatment is a common problem in alcohol dependence. However, its prediction still lacks reliability. We here investigated whether the easily accessible clinical Cloninger and Lesch classifications predict alcohol-related hospital readmission following inpatient withdrawal treatment. METHODS: In this bicentric prospective clinical study, 67 female and 84 male alcohol-dependent inpatients were characterized according to the Cloninger items and the Lesch typology. The patients' records were followed for 24 months. Because of the well-established sex differences in alcohol dependence, we studied females and males separately. RESULTS: Overall, 54% of the female patients and 67% of the male patients sustained at least 1 alcohol-related hospital readmission during the follow-up. Readmission was related to a higher Cloninger type 2 score than nonreadmission (females, p = 0.007, males p = 0.044). In females, the Cloninger type 2 score correlated with the number of readmissions (ρ = 0.384, p = 0.001) and the days to first readmission (ρ = -0.333, p = 0.006). The effects were stronger in patients with age at onset of alcohol dependence over 25 years. We found gender dimorphisms concerning the Cloninger items. In female patients, the 4 Lesch subtypes differed in their risk (p = 0.010), the number (p = 0.040), and the days to first readmission (p = 0.031). Lesch type 1 was associated with an increased risk (OR = 4.83, p = 0.041) and Lesch type 2 with a reduced risk (OR = 0.07, p = 0.004). In addition, the number of previous inpatient alcohol withdrawals predicted the patients' outcomes (p < 0.05). CONCLUSIONS: The Cloninger type 2 score and the Lesch typology are promising tools for the prediction of alcohol-related readmissions. Our findings provide the basis to optimize relapse prevention in alcohol dependence.

DNA methylation of the LEP gene is associated with craving during alcohol withdrawal.

Different studies have described evidence for an association between leptin serum levels and craving in alcohol dependent patients. As leptin expression is regulated by DNA methylation we investigated changes of DNA methylation of the LEP gene promoter region in alcohol dependent patients undergoing withdrawal. Results show that low methylation status is associated with increasing serum leptin levels and elevation of craving for alcohol in the referring patients group. These findings point towards a pathophysiological relevance of changes in DNA methylation of the LEP gene promoter region in alcohol dependence.