Levels of IL-6 are Associated with Lifetime Attempted Suicide in Alcohol Use Disorder Patients.

Background: Patients with alcohol use disorder (AUD) have an increased risk of suicide. Neuroimmunological measures, such as cytokines, are shown to deviate in people with attempted suicide. Few studies have investigated this among AUD patients. Patients and Methods: One-hundred and fourteen patients undergoing residential treatment for AUD were interviewed on lifetime suicide attempts (SA) along with several other background variables and clinical characteristics. Serum blood samples were drawn for analysis of cytokines. Results: Thirty-one patients (27%) reported at least one SA. These patients had more symptoms of current affective disorders and more severe dependence. In bivariate analysis only IL-6 and IL-10 appeared to be associated with lifetime SA but without reaching statistical significance. In multivariate linear regression, adjusting for sex, nicotine use, somatic illness, and the use of anti-inflammatory drugs, IL-6 was associated to SA (p = 0.033). Conclusion: The cytokine IL-6 has repeatedly been found to be associated with suicidality. The present study concurs with this role of IL-6 in a naturalistic observational study of AUD patients.

Inflammatory cytokines in alcohol use disorder patients are lower in smokers and users of smokeless tobacco.

BACKGROUND: Smoking and alcohol use often co-occur, and the use of nicotine-containing products is particularly common among persons with alcohol use disorder (AUD). Recent evidence shows that chronic alcohol use leads to inflammation through increased gut permeability and dysregulated cytokine levels. While cigarette smoking also has detrimental health effects, nicotine has immune dampening effects in some settings. Preclinical evidence demonstrates that nicotine can dampen alcohol-induced inflammation, but inflammatory responses after nicotine use has not been studied in persons with AUD. This study compared the level of circulating cytokines in abstinent AUD inpatients who were non-tobacco users, smokers, users of Swedish snus, or dual tobacco users. METHODS: We collected blood samples and information about somatic and mental health and tobacco habits from 111 patients in residential treatment for AUD and 69 healthy controls. Levels of interferon (IFN)-γ, interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-17a, IL-1ß, IL-6, IL-8, IL-1 receptor antagonist (ra), and monocyte chemoattractant protein (MCP)-1 were examined using a multiplex assay. RESULTS: Patients with AUD had higher levels of seven cytokines than healthy controls. Among the AUD patients, nicotine users had lower levels of IL-10, TNF-α, IL-17a, IL-1ß, IL-8, and MCP-1 (all p < 0.05). CONCLUSIONS: Our findings may indicate that nicotine has anti-inflammatory effects in patients with AUD. Nonetheless, nicotine use cannot be recommended as a viable therapeutic option to reduce alcohol-induced inflammation because of its other adverse effects. Additional studies of the effects of tobacco or nicotine products on cytokine patterns in relation to mental or somatic health conditions are warranted.

The Self-Rated Effects of Alcohol Are Related to Presystemic Metabolism of Alcohol.

AIMS: A high number of alcohol units required to feel a subjective effect of alcohol predicts future alcohol use disorders (AUDs). The subjective response to alcohol can be measured using the validated retrospective self-rated effects of alcohol (SRE) questionnaire. Few studies have investigated the specific relationship between SRE and blood alcohol concentration (BAC) in an experimental setting. METHODS: Twenty healthy young adult male volunteers who had experience with binge drinking, but did not have AUD, filled out the SRE-questionnaire and were served with a fixed amount of alcohol per body weight. BACs were measured throughout a 12-hour period, reaching a maximum BAC of ~0.13%. Median split of SRE-scores was utilized to compare BACs among participants with relatively high effects (low SRE) and relatively low effects (high SRE) of alcohol. RESULTS: Participants reporting a relatively low SRE-score had a statistically significant higher measured BAC at all time points until alcohol was eliminated. This was especially pronounced during the first 2 hours after alcohol (P = 0.015) without a significant difference in the alcohol elimination rate being detected. CONCLUSION: The study indicates that a self-ated SRE-score is related to BACs after the ingestion of a standardized amount of alcohol per body weight. Reporting a higher number of alcohol units before feeling an effect was related to a lower BAC. As the differences in BAC between relatively high and low self-rated effects appeared rapidly after intake, this could be interpreted as an effect of presystemic metabolism of alcohol.

Longitudinal determinants of insomnia among patients with alcohol use disorder.

Insomnia is common among patients with AUD and can impair quality of life and cognitive functioning, as well as cause psycho-social problems and increased risk of relapse. Nonetheless, determinants of insomnia in patients with AUD have scarcely been studied. We aimed to examine prevalence and development of self-perceived insomnia among inpatients in treatment for AUD, and to examine factors in this group known to be associated with sleep disturbance in the general population. We examined self-reported information about sleep from 94 AUD inpatients in long-term treatment (up to 9 months) using a questionnaire identifying probable insomnia. Potential predictors identified in bivariate tests were used in binomial logistic regressions to examine the effect on sleep at baseline and at 6-week follow-up. Longitudinal multilevel analyses were used to examine factors affecting development of sleep quality during the treatment stay. At baseline, 54% of the patients reported sleep problems indicating insomnia. This was reduced to 35% at 6-week follow-up. In a cross-sectional analysis of sleep at baseline, we found that being male (OR 0.18, p = 0.042) and engaging in physical activity (OR 0.09, p < 0.001) were negatively associated with insomnia, while a high level of depressive symptoms (OR 1.10, p = 0.010) was positively associated after adjustment for age, history of trauma, and severity of dependence. Multilevel analyses of data over a 6-month period showed time interactions with physical activity, such that sleep improvement was greater in patients who initially had a low level of physical activity. This longitudinal study corroborates findings of high prevalence of insomnia among AUD patients and identifies factors in this group associated with insomnia, such as sex, depression, and physical activity. Future longitudinal studies are needed to examine the causal directions between sleep, depression, and physical activity and how these might be targeted in clinical settings.

History of Delirium Tremens in AUD Patients in Treatment: Relationship to AUD Severity and Other Factors.

Introduction: Delirium tremens (DT) occurs after stopping prolonged, high alcohol intake and may be life-threatening if untreated. We need to know about clinical correlates of DT in order to provide the best clinical care. Methods: At admission to inpatient treatment a cohort of 114 alcohol use disorder (AUD) patients were interviewed and examined concerning psychiatric diagnosis and symptoms, trauma experiences and alcohol related measures and if they had experienced DT. Results: Twenty-four percent of the patients reported a life-time experience of DT. These patients were predominantly males and had lower educational level. More of the patients in the DT than the non-DT group reported at least one suicide attempt, were diagnosed with PTSD, and dropped out of treatment. Also, having parents with alcohol problems was more common among these patients, and they reported a longer duration of problematic drinking and a higher number of drinks needed to feel an effect of drinking. In the multivariable adjusted analysis only a diagnosis of PTSD (OR=5.71; 95% confidence interval (CI): 1.34-24.31) and duration of problematic drinking with a 6% increase in risk for every year (OR=1.06; 95% CI: 1.01-1.11) remained significant risk factors for having DT experience. Discussion and conclusion: Having experienced DT was more prevalent in the current investigation than in earlier studies. Patients that had experienced DT seemed to have more serious AUD, especially signified by a longer duration of drinking. These patients seemed to have many clinical disadvantages including more drop-out and higher suicide rate. PTSD could be a risk factor for DT but may also follow the DT experience.

GABAA subunit single nucleotide polymorphisms show sex-specific association to alcohol consumption and mental distress in a Norwegian population-based sample.

Little is known about genetic influences on the relationship between alcohol consumption and mental distress in the general population, where the majority report consumption and distress far below diagnostic thresholds. This study investigated single nucleotide polymorphisms (SNPs) from candidate gene studies on alcohol use disorder and depressive disorders, for association with alcohol consumption and with mental distress in a population-based sample from the Cohort of Norway (n = 1978, 49% women). The relationship between alcohol consumption and mental distress was further examined for genotype modification. There was a positive correlation between mental distress and alcohol consumption in men, as well as an association between SNPs and mental distress in men (GABRG1, GABRA2, DRD2, ANKK1, MTHFR) and women (CHRM2, MTHFR) and between SNPs and alcohol consumption in women (GABRA2, MTHFR). No modification by SNP genotype was found on the relationship between alcohol consumption and mental distress. The association between mental distress and GABRG1 in men remained significant after correcting for multiple comparisons. The results indicate that alcohol consumption and mental distress are associated in the general population even at levels below clinical thresholds and point to SNPs in genes related to GABAergic signalling for level of mental distress in men.