2-Arachidonoylglycerol-mediated endocannabinoid signaling modulates mechanical hypersensitivity associated with alcohol withdrawal in mice

Background

Alcohol use disorder (AUD) commonly occurs in patients with chronic pain, and a major barrier to achieving abstinence and preventing relapse is the emergence of hyperalgesia during alcohol withdrawal. Elucidating novel therapeutic approaches to target hyperalgesia associated with alcohol withdrawal could have important implications for treating AUD. Here, we examined the role of 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid (eCB) signaling in the regulation of hyperalgesia associated with alcohol withdrawal in mice. We tested the hypothesis that pharmacological augmentation of 2-AG signaling could reduce hyperalgesia during withdrawal.

Methods

Male and female C57BL/6J mice were tested during withdrawal from a continuous access two-bottle choice (2BC) paradigm to investigate how eCB signaling modulates mechanical and thermal sensitivity during withdrawal. Mice were pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184 to elevate levels of 2-AG. Rimonabant or AM630 were given to block CB₁ and CB₂ receptor activity, respectively. DO34 was given to reduce 2-AG by inhibiting the 2-AG synthetic enzyme diacylglycerol lipase (DAGL).

Results

After 72 h of withdrawal, male and female mice exhibited increased mechanical, but not thermal, hypersensitivity, which normalized by 7 days. This effect was reversed by pretreatment with JZL184. The effects of JZL184 were prevented by coadministration of either the CB₁ or the CB₂ antagonist. DO34, Rimonabant, and AM630 exacerbated mechanical hypersensitivity during alcohol withdrawal, causing an earlier onset and persistent hypersensitivity even 1 week into withdrawal.

Conclusions

Our findings demonstrate the critical role of 2-AG signaling in the bidirectional regulation of mechanical sensitivity during alcohol withdrawal, with enhancement of 2-AG levels reducing sensitivity, and inhibition of 2-AG signaling exacerbating sensitivity. These data suggest that 2-AG augmentation represents a novel approach to the treatment of alcohol withdrawal-associated hyperalgesia and AUD in patients with comorbid pain disorders.

     

Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease

Increased oxidative stress (SOX), inflammation and prevalence of cardiovascular disease (CVD) have been reported in end-stage renal disease (ESRD), but their associations with kynurenine (KYN) pathway activation remain unknown. We determined the plasma concentrations of tryptophan (TRP), KYN, 3-hydroxykynurenine (3-HKYN); two distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD) and total peroxide; and high sensitivity C-reactive protein (hs CRP) as a indicator of inflammation in 146 ESRD patients and healthy controls. Analysis of TRP degradation through the KYN pathway demonstrated that in uremia the concentrations of this aminoacid were decreased by 40-60% in comparison with controls. In contrast, the plasma levels of KYN and 3-HKYN in ESRD patients were increased by 32-96% and 184-306%, respectively. These changes were accompanied by significant increase in the kyn/trp ratios by 140-240%, and 3-hkyn/kyn ratios by 40-154% in uremics compared to controls. ESRD patients showed a significant increase in Cu/Zn SOD, total peroxide and hs CRP levels between controls and all patients group. KYN and 3-HKYN were positively associated with inflammation and SOX markers in uremics. Logistic regression analysis showed that age, gender, presence of DM (all p<0.001), elevated hs CRP (p<0.01) and 3-HKYN levels (p<0.05) were independently associated with the presence of CVD in this population. These results suggest a relationship between KYN pathway activation and increased SOX, inflammation and CVD prevalence in ESRD patients.     

Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption,and broader externalizing behavior in humans

Background

Individual variation in the physiological response to alcohol is predictive of an individual's likelihood to develop alcohol use disorder (AUD). Evidence from diverse model organisms indicates that the levels of long-chain polyunsaturated omega-3 fatty acids (ω-3 LC-PUFAs) can modulate the behavioral response to ethanol and therefore may impact the propensity to develop AUD. While most ω-3 LC-PUFAs come from diet, humans can produce these fatty acids from shorter chain precursors through a series of enzymatic steps. Natural variation in the genes encoding these enzymes has been shown to affect ω-3 LC-PUFA levels. We hypothesized that variation in these genes could contribute to the susceptibility to develop AUD.

Methods

We identified nine genes (FADS1, FADS2, FADS3, ELOVL2, GCKR, ELOVL1, ACOX1, APOE, and PPARA) that are required to generate ω-3 LC-PUFAs and/or have been shown or predicted to affect ω-3 LC-PUFA levels. Using both set-based and gene-based analyses we examined their association with AUD and two AUD-related phenotypes, alcohol consumption, and an externalizing phenotype.

Results

We found that the set of nine genes is associated with all three phenotypes. When examined individually, GCKR, FADS2, and ACOX1 showed significant association signals with alcohol consumption. GCKR was significantly associated with AUD. ELOVL1 and APOE were associated with externalizing.

Conclusions

Taken together with observations that dietary ω-3 LC-PUFAs can affect ethanol-related phenotypes, this work suggests that these fatty acids provide a link between the environmental and genetic influences on the risk of developing AUD.

     

Improvement in quality of life among women and men aged 60 years and older following treatment for alcohol use disorder

Background

Previous studies have yielded mixed results on the association between gender and alcohol use disorder (AUD) treatment outcomes. Thus, additional research is needed to determine the effect of gender on AUD treatment outcomes, including quality of life (QoL), particularly among older adults.

Aims

In a clinical sample of older adults with DSM-5 AUD, we examined changes in QoL from the beginning of AUD treatment through 1 year of follow-ups. We also examined the effect of gender and explored interaction effects with gender on QoL.

Methods

We utilized data from the “Elderly Study,” a multi-national, single-blind, randomized, controlled trial of 693 adults aged 60+ with DSM-5 AUD. Alcohol use was assessed with the Form-90, and QoL with the brief version of the World Health Organization QoL measure. Information was collected at treatment initiation and at 4-, 12-, 26-, and 52-week follow-ups. Multilevel mixed-effects logistic and linear regression models were used to examine QoL changes and the effect of gender on changes in QoL.

Results

Following treatment, small, but significant improvements were seen over time in overall perceived health (p < 0.05). Improvements that persisted over the 1-year follow-up period were seen in the QoL domains of physical health (β: 2.6, 95% CI: 1.4–3.9), psychological health (β: 3.5, 95% CI: 3.3–3.8), social relationships (β: 4.0, 95% CI: 2.5–5.6), and environmental health (β: 1.4, 95% CI: 0.4–2.4). No significant changes were seen over time in overall perceived QoL (p = 0.58). Gender was not associated with changes in any of the QoL outcome measures (all p ≥ 0.05).

Conclusions

Among 60+ year-old adults receiving treatment for DSM-5 AUD, improvements in QoL were achievable and maintained over time, but were not associated with gender.     

Emotion differentiation in early recovery from alcohol use disorder: Associations with in-the-moment affect and 3-month drinking outcomes

Background

Early recovery from alcohol use disorder (AUD) is commonly associated with high levels of negative affect, stress, and emotional vulnerability, which confer significant relapse risk. Emotion differentiation—the ability to distinguish between discrete emotions—has been shown to predict relapse after treatment for a drug use disorder, but this relationship has not been explored in individuals recovering from AUD.

Methods

The current study used thrice daily random and up to thrice daily self-initiated ecological momentary assessment surveys (N = 42, observations = 915) to examine whether 1) moments of high affective arousal are characterized by momentary differences in emotion differentiation among individuals in the first year of a current AUD recovery attempt, and 2) individuals’ average emotion differentiation would predict subsequent alcohol use measured by the timeline follow-back over a 3-month follow-up period.

Results

Multilevel models showed that moments (Level 1) of higher-than-average negative affect (p < 0.001) and/or stress (p = 0.033) were characterized by less negative emotion differentiation, while moments of higher-than-average positive affect were characterized by greater positive emotion differentiation (p < 0.001). At the between-person level (Level 2), participants with higher stress overall had lower negative emotion differentiation (p = 0.009). Linear regression showed that average negative, but not positive, emotion differentiation was inversely associated with percent drinking days over the subsequent 3-month follow-up period (p = 0.042). Neither form of average emotion differentiation was associated with drinking quantity.

Conclusions

We found that for individuals in early AUD recovery, affective states are associated with acute shifts in the capacity for emotion differentiation. Further, we found that average negative emotion differentiation prospectively predicts subsequent alcohol use.

     

Impact of Long-Term Alcohol Consumption and Relapse on Genome-Wide DNA Methylation Changes in Alcohol-Dependent Subjects: A Longitudinal Study

Background

Genetic factors play an important role in the development and maintenance of alcohol use disorder (AUD). Significant and widespread differences in methylation levels of multiple regions within the genome have been reported between AUD patients and healthy controls in large epigenome-wide association studies (EWASs). Also, within patient populations, methylation changes over time (both during and after withdrawal) have been identified as sensitive indicators for disease activity. The detection of changes in methylation levels is a powerful tool to further explore and understand the biological correlates and underpinnings of AUD. Although there is strong and convincing evidence for differences in methylation of various sites between AUD patients and controls, only few studies assessed changes within patients over longer periods of time while taking into account alcohol consumption, relapse, and abstinence. So far, the longest period assessed as a within-subject design using EWASs was 4 weeks.

Methods

Here, we investigated changes in whole-genome methylation levels within a sample of 69 detoxified AUD patients over a period as long as 12 months for the first time, comparing patients that relapsed within the follow-up period to those that remained abstinent.

Results

Whole-genome methylation patterns of individual CpG sites over time did not differ between abstinent and relapsing patients. However, there was a negative association between global mean methylation at the 12-month follow-up and alcohol consumption within our sample.

Conclusion

Although the present study represents the largest study of methylation levels in a sample of AUD patients with a follow-up period of 1 year and accounting for alcohol consumption and relapse to date, the sample size might still not be large enough to detect genome-wide significant effects. Therefore, large-scale, long-term studies with AUD subjects are needed to determine the utility of DNA methylation for the assessment and monitoring of persons with alcohol use disorders.

     

Resting state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study

Background

Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation.

Materials and Methods

Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network.

Results

At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward).

Conclusions

Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

     

Stigmatization of people with alcohol use disorders: An updated systematic review of population studies

Background

We summarize research on the public stigmatization of persons with alcohol use disorder (AUD) in comparison with other mental health conditions and embed the results into a conceptual framework of the stigma process.

Methods

We conducted a systematic search using Embase, MEDLINE, PubMed and PsycINFO (via Ovid), and Web of Science for population-based studies on the public stigma in AUD and at least 1 other mental health condition, published between October 1, 2010 and December 20, 2020, thus including all studies published since the last systematic review on this topic. The study is registered with PROSPERO (registration number: CRD42020173054).

Results

We identified 20,561 records, of which 24 met the inclusion criteria, reporting results from 16 unique studies conducted in 9 different countries. Compared to substance-unrelated mental disorders, persons with AUD were generally less likely to be considered mentally ill, while they were perceived as being more dangerous and responsible for their condition. Further, the public desire for social distance was consistently higher for people with AUD. We found no consistent differences in the public stigma toward persons with AUD in comparison with other substance use disorders.

Conclusion

The stigmatization of persons with AUD remains comparatively high and is distinct from that of other substance-unrelated disorders.

     

Hyperfibrinolysis,uPA/suPAR System,Kynurenines, and the Prevalence of Cardiovascular Disease in Patients With Chronic Renal Failure on Conservative Treatment

BackgroundDisturbances of the fibrinolytic system and kynurenine (KYN) pathway of tryptophan (TRP) metabolism have been postulated as important factors in the pathogenesis of cardiovascular disease (CVD). However, no data are yet available on the associations between these 2 systems in relation to CVD prevalence in patients with chronic renal failure (CRF).MethodsWe evaluated TRP and its metabolites, KYN, 3-hydroxykynurenine, and quinolinic acid (QA), and their relations with the parameters of the fibrinolytic system, such as tissue-type plasminogen activators and urokinase-type (uPA) plasminogen activators, plasmin-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1, and Cu/Zn superoxide dismutase (Cu/Zn SOD) levels as the marker of oxidative stress in a population of 50 patients with CRF and 20 healthy controls. In addition, the relations of these parameters to CVD prevalence in patients with CRF were also determined.ResultsCompared with controls, the CRF group had significantly increased KYNs, PAP, uPA, soluble urokinase PA receptor (suPAR), plasminogen activator inhibitor-1 (all P < 0.0001), and tissue-type plasminogen activators (P < 0.01) concentrations. TRP levels were significantly lower (P < 0.0001), whereas Cu/Zn SOD levels did not differ significantly between patients with CRF and controls. An accelerated PAP formation was positively correlated with age, inflammatory state, creatinine, uPA/suPAR system, 3-hydroxykynurenine, QA, Cu/Zn SOD, and CVD prevalence, whereas it was inversely associated with TRP levels and estimated glomerular filtration rate. Multivariable analysis confirmed that QA, TRP, suPAR, and Cu/Zn SOD levels were the independent variables significantly associated with the hyperfibrinolytic state in patients with CRF.ConclusionsThis crosssectional study has demonstrated that hyperfibrinolysis was associated with uPA/suPAR system, KYNs, oxidative status, and CVD prevalence in patients with CRF.     

Social networks and alcohol use disorders: findings from a nationally representative sample

Background: While some argue that social network ties of individuals with alcohol use disorders (AUD) are robust, there is evidence to suggest that individuals with AUDs have few social network ties, which are a known risk factor for health and wellness. Objectives: Social network ties to friends, family, co-workers and communities of individuals are compared among individuals with a past-year diagnosis of alcohol dependence or alcohol abuse to individuals with no lifetime diagnosis of AUD. Method: Respondents from Wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) were assessed for the presence of past-year alcohol dependence or past-year alcohol abuse, social network ties, sociodemographics and clinical characteristics. Results: Bivariate analyses showed that both social network size and social network diversity was significantly smaller among individuals with alcohol dependence, compared to individuals with alcohol abuse or no AUD. When social and clinical factors related to AUD status were controlled, multinomial logistic models showed that social network diversity remained a significant predictor of AUD status, while social network size did not differ among AUD groups. Conclusion: Social networks of individuals with AUD may be different than individuals with no AUD, but this claim is dependent on specific AUD diagnosis and how social networks are measured.     

Lifetime alcohol intake and pattern of alcohol consumption in patients with alcohol-induced pancreatitis in comparison with patients with alcohol use disorder

Objective: To examine lifetime drinking patterns in men and women with alcohol-induced pancreatitis (AIP) in comparison with patients with alcoholic use disorder (AUD) without pancreatic disease.

Methods: Alcohol consumption patterns were assessed using a validated questionnaire, the Lifetime Drinking History (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for gender and age (+/? 5 years) with patients with AUD in addiction treatment.

Results: A total of 45 patients with AIP (35 males, 10 females) and 45 AUD patients were included. Alcohol consumption patterns were not significantly different between males and females with AIP and those with history of acute AIP and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD patients were similar in terms of onset age and duration of alcohol consumption, lifetime alcohol intake and drinks per drinking day. A higher proportion of binge drinking was found among patients with AUD than those with AIP (median 1.00 vs. 0.94, p?=?.01). Males with AUD had lower onset age (15 vs. 16 years, p?=?.03), higher total amount of spirits (35520 vs. 10450 drinks, p?=?.04) and higher proportion of binge drinking (1.00 vs. 0.97, p?=?.01) than males with AIP, whereas females with AIP and AUD had similar drinking patterns.

Conclusions: Alcohol drinking patterns and lifetime drinking history was similar in patients with AIP and patients with AUD. Males with AIP had lower total amount of spirits and lower proportion of binge drinking than those with AUD, suggesting the idiosyncratic etiology of AIP.     

Dialectical behaviour therapy skills training for the treatment of addictive behaviours among individuals with alcohol use disorder: the effect of emotion regulation and experiential avoidance

ABSTRACT

Backgrounds

Dialectical behavior therapy skills training (DBT-ST) is an effective treatment for alcohol use disorder (AUD). AUD frequently co-occurs with other addictive behaviors.     

Mecamylamine treatment for alcohol dependence: a randomized controlled trial

Background and aims

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects.

Design

Out‐patient, randomized, double‐blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63).

Setting

Connecticut, USA.

Participants

Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non‐smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel.

Measurements

Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects.

Findings

There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F_{1, 100} = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = ?8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions.

Conclusions

Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment‐seeking smokers and non‐smokers with alcohol use disorder.     

Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders

BACKGROUND: Previous studies have suggested neural disruption and reorganization in young and older adults with alcohol use disorders (AUD). However, it remains unclear at what age and when in the progression of AUD changes in brain functioning might occur. METHODS: Alcohol use disordered (n = 15) and nonabusing (n = 19) boys and girls aged 15 to 17 were recruited from local high schools. Functional magnetic resonance imaging data were collected after a minimum of 5 days' abstinence as participants performed spatial working memory and simple motor tasks. RESULTS: Adolescents with AUD showed greater brain response to the spatial working memory task in bilateral parietal cortices and diminished response in other regions, including the left precentral gyrus and bilateral cerebellar areas (clusters > or =943 microl; p < 0.05), although groups did not differ on behavioral measures of task performance. No brain response differences were observed during a simple finger-tapping task. The degree of abnormality was greater for teens who reported experiencing more withdrawal or hangover symptoms and who consumed more alcohol. CONCLUSIONS: Adolescents with AUD show abnormalities in brain response to a spatial working memory task, despite adequate performance, suggesting that subtle neuronal reorganization may occur early in the course of AUD.     

Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells

Abstract

Background. Kynurenic acid (KYNA), a tryptophan metabolite, was found in human saliva, gastric juice, bile, pancreatic juice and mucus of rat small intestine. Methods. KYNA content in mucus aspirated from human caecum or colon ascendens and KYNA production in colon epithelial and cancer cells were determined using HPLC. Moreover, biological properties of KYNA and kynurenine aminotransferases (KATs) expression in colon epithelial and colon cancer cells were studied. Results. Considerably higher KYNA concentration was detected in samples from patients diagnosed with colon carcinoma (269.40 ± 107.00 pmol/ml, N = 4), Adenoma tubulovillosum (200.50 ± 36.72, N = 10) or Adenoma tubulare (243.50 ± 38.09, N = 9) than in control group (82.22 ± 7.61 pmol/ml, N = 30). Moreover, colon epithelium CCD 841 CoTr cells actively synthesized KYNA in a concentration- and time-dependent manner. This process was decreased by aminooxyacetic acid and L-glutamate in opposite to 4-aminopyridine treatment. Interestingly, KYNA production in colon cancer cells (HT-29 1.39 ± 0.27, LS-180 1.18 ± 0.15 and Caco-2 4.21 ± 0.30 pmol/1 × 10⁵ cells/2 h) was considerably higher in comparison to normal colon epithelial cells (0.70 ± 0.07 pmol/1 × 10⁵ cells/2 h). However, KATs I and II were expressed at similar level in both colon epithelium and cancer cells. Furthermore, KYNA exerted an antiproliferative effect at higher micro- and milimolar concentrations against colon cancer cells with the IC₅₀ of 0.9, 0.2 and 1.2 mM for HT-29, LS-180 and Caco-2 cells, respectively. Conclusion. Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.     

Lifetime drinking history in patients with alcoholic liver disease and patients with alcohol use disorder without liver disease

Objective: To determine the differences in lifetime alcohol intake (LAI) and drinking patterns between patients with alcoholic liver disease (ALD) and alcohol use disorder (AUD) without notable liver injury and between males and females with ALD.

Methods: Alcohol drinking patterns were assessed using the Lifetime Drinking History (LDH) a validated questionnaire, during an outpatient visit. Patients with AUD, currently in addiction treatment, were matched for gender and age (±5 years) with the ALD group.

Results: A total of 39 patients with ALD (26 males and 13 females; median age 58) and equal number of AUD patients were included (median age 56 years). The onset age for alcohol drinking and duration of alcohol consumption was similar in ALD and AUD. The number of drinking days was higher in women with ALD than in women with AUD: 4075 [(3224–6504) versus 2092 (1296–3661), p?=?.0253]. The LAI and drinks per drinking day (DDD) were not significantly different between patients with ALD and AUD. Females with ALD had lower LAI than males with ALD: 32,934 (3224–6504) versus 50,923 (30,360–82,195), p?=?.0385, fewer DDD (p?=?.0112), and lower proportion of binge drinking as compared to males with ALD (p?=?.0274).

Conclusions: The total LAI was similar in patients with ALD and AUD. The number of drinking days over the lifetime was associated with the development of ALD in females. Females with ALD had significantly lower alcohol consumption than men with ALD despite similar duration in years of alcohol intake which supports the concept of female propensity of ALD.     

The effect of pre-existing alcohol use disorder on the risk of developing posttraumatic stress disorder: results from a longitudinal national representative sample

ABSTRACT

Background: There is inconsistent evidence in the literature as to whether or not Alcohol Use Disorder (AUD) is a risk factor for Post-Traumatic Stress Disorder (PTSD).

Objectives: We evaluated the risk of developing PTSD after trauma exposure in individuals with AUD. As a secondary analysis, we also tested if alcohol dependence or alcohol abuse separately increased the risk of PTSD development. We also explored the effect of AUD on exposure to various traumas.

Methods: Longitudinal data was obtained from 30,180 individuals with and without AUD from National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) waves I and II. Using propensity score methods, we matched individuals with AUD (alcohol abuse and/or dependence using DSM-IV criteria) to those without AUD at baseline on demographic, familial, and clinical factors to estimate the risk of PTSD development after trauma exposure. Data were adjusted for complex survey methods.

Results: Individuals with AUD had an increased risk of being exposed to various traumas between wave I and II (60.6% vs. 48.3% of controls). Among individuals exposed to trauma between the two waves (N = 14,107), AUD had no effect on subsequent PTSD development after matching and controlling for covariates (OR: 1.00; 95%CI: 0.72–1.39; p = .99). However, those with alcohol dependence only did have an effect on subsequent PTSD development (OR: 1.76; 95%CI: 1.05–2.95; p = .03).

Conclusion: In individuals with alcohol dependence the experience of trauma increases the risk of developing PTSD. These findings suggest that prevention methods from PTSD after trauma exposure for individuals with alcohol dependence are needed.