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AimsBrain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors.MethodsData from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model.ResultsNo significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = −0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found.ConclusionOur study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker.

Background Young adults with chronic pain and symptoms experience disruptions to their social, emotional, physical, and vocational functioning. Interdisciplinary pain rehabilitation programs for pediatric and adult populations are not designed specifically to address the developmental needs of young adults. Methods This article describes the development of a novel intensive interdisciplinary outpatient rehabilitation program tailored to the unique needs of young adults with chronic pain and symptoms. Tailored content included vocational assessment and consultation, financial literacy education, and sexual health education. Results Outcome data demonstrate treatment gains, with reductions in pain interference, pain severity, pain catastrophizing, and depressive symptoms, as well as improvements in mental and physical quality of life, perceived performance, perceived satisfaction with performance, and objective measures of physical functioning. Conclusions The article concludes with clinical recommendations for the management of chronic pain and symptoms in young adults, applicable across multiple treatment settings.

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (β = -0.16, p = 0.0012) but not in women (β = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies.

During the current coronavirus disease 2019 epidemic, many outpatient chemical dependency treatment programs and clinics are decreasing their number of in-person patient contacts. This has widened an already large gap between patients with substance use disorders (SUDs) who need treatment and those who have actually received treatment. For a disorder where group therapy has been the mainstay treatment option for decades, social distancing, shelter in place, and treatment discontinuation have created an urgent need for alternative approaches to addiction treatment. In an attempt to continue some care for patients in need, many medical institutions have transitioned to a virtual environment to promote safe social distancing. Although there is ample evidence to support telemedical interventions, these can be difficult to implement, especially in the SUD population. This article reviews current literature for the use of telehealth interventions in the treatment of SUDs and offers recommendations on safe and effective implementation strategies based on the current literature.

Context Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear. Objective To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain. Design Cross-sectional study, 2016-2018. Setting Referral center. Patients Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center. Main outcome measure Diagnosis of OIAI was considered if positive case detection (cortisol Results In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking 20 mg); however, specificity of MME cutoff >20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function. Conclusion The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.

We assessed the impact of comorbid depression and anxiety disorders as well as positive and negative emotional states on alcohol consumption in alcohol dependent men and women.Per day alcohol consumption during 90 days before enrolment was assessed by the Time Line Follow Back (TLFB) in 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Propensity to drink in negative/positive emotional states was assessed using the Inventory of Drug Taking Situations (IDTS). Psychiatric comorbidities, including major depressive disorder (MDD), substance-induced depression (SID), anxiety disorders (AnxD), or substance-induced anxiety (SIA) were identified by Psychiatric Research Interview of Substance and Mood Disorders (PRISM).In the combined group, increased number of drinks per day and number of heavy drinking days correlated with increased IDTS scores (all p 0.0001), while the lifetime history of MDD was associated with fewer drinking days (p = 0.045) but not average number of drinks per day. Male sex was associated with higher alcohol consumption per day (p 0.0001), but not with the number of drinking days (p 0.05). Lifetime MDD history was associated with less drinking days (p = 0.0084) and less heavy drinking days (p = 0.021) in alcohol dependent men, while current MDD was associated with higher alcohol use per day in alcohol dependent women (p = 0.044).Our findings suggest that emotional states and lifetime MDD history have sex-specific impact on alcohol use in alcohol dependent men and women. The mechanisms underlying these findings and their relevance to treatment outcomes need to be examined in future studies.

Wernicke encephalopathy (WE) was first described by Carl Wernicke in 1881. WE is caused by thiamine deficiency. Alcoholism is the most common etiologic factor associated with WE in the United States, but it can occur in any patient with a nutritional deficiency state such as hyperemesis gravidarum, intestinal obstruction, and malignancy. WE is a clinical diagnosis. The common findings include mental status changes, ocular dysfunction, and a gait apraxia, present in only 10% of cases. Only a few cases of WE are diagnosed before death. Approximately 80% of patients with untreated WE have development of Korsakoff syndrome, which is characterized by memory impairment associated with confabulation. The initial clinical diagnosis of WE is critical, keeping in mind that the classic triad of symptoms is often absent. Recognition of nutritional deficiency and any portion of the classic triad should prompt treatment. Additionally, hypothermia, hypotension, and coma should raise clinical suspicion for the disease. Primary treatment includes timely administration of thiamine, for which the route and dosage remain controversial. Clinical judgment should be exercised in diagnosis and treatment (dosage, frequency, route of administration and duration) in all cases of WE. Overdiagnosis and overtreatment may be preferred to prevent prolonged or persistent neurocognitive impairments given the excellent safety profile of thiamine. Further prospective research is warranted to better understand the disease biology, risk factors, and treatment recommendations.

Despite current guideline recommendations against the use of opioids for the treatment of fibromyalgia pain, opioid use is reported in approximately 30% of the patient population. There is a lack of information describing the process and results of tapering of chronic opioids. The purpose of this study is to describe opioid tapering and withdrawal symptoms in fibromyalgia patients on opioids.This retrospective research study included a baseline analysis of 159 patients consecutively admitted to the Mayo Clinic Pain Rehabilitation Center from 2006 through 2012 with a pain diagnosis of fibromyalgia completing a 3-week outpatient interdisciplinary pain rehabilitation program. Opioid tapering analysis included 55 (35%) patients using daily opioids.Opioid tapering was individualized to each patient based on interdisciplinary pain rehabilitation team determination. Opioid withdrawal symptoms were assessed daily, utilizing the Clinical Opioid Withdrawal Scale.Patients taking daily opioids had a morphine equivalent mean dose of 99 mg/day. Patients on 100 mg/day were tapered off over a mean of 10 days compared with patients on 200 mg/day over a mean of 28 days (P0.001). Differences in peak withdrawal symptoms were not statistically significant based on the mean equivalent dose (P = 22). Patients taking opioids for2 years did not differ in length of tapering (P =0.63) or peak COWS score (P =0.80) compared with2 years duration. Patients had significant improvements in pain-related measures including numeric pain scores, depression catastrophizing, health perception, interference with life, and perceived life control at program completion.Fibromyalgia patients on higher doses of opioids were tapered off over a longer period of time but no differences in withdrawal symptoms were seen based on opioid dose. Duration of opioid use did not affect the time to complete opioid taper or withdrawal symptoms. Despite opioid tapering, pain-related measures improved at the completion of the rehabilitation program.

This quality improvement project demonstrates that RN Care Managers, in a chronic pain programme, can assess for a family history of substance abuse in 5-10 min. Information informs treatment based on specific high risk criteria. Benefits include heightened awareness of the genetic and environmental risks associated with a family history of substance abuse, an opportunity to participate in motivational interventions to prevent or minimize consequences of substance use disorders, and likely substantial overall health-care cost savings.

Objective The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. Methods Retrospective study of electronic medical records for all patients 30–60 years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. Results Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [ n = 29 (70.7%) vs. n = 35 (28.7%) p p = 0.002). On average, RYGB patients reported resuming alcohol consumption 1.4 ± 0.2 years post-surgery, meeting criteria for AUD at 3.1 ± 0.5 years and seeking treatment at 5.4 ± 0.3 years postoperatively. Pre-surgical drinks per day were significantly fewer compared to post-surgical consumption [2.5 ± 0.4 vs. 8.1 ± 1.3, p = 0.009]. Prior to admission, RYGB patients reported fewer drinking days per week vs. controls (4.7 ± 0.3 vs. 5.5 ± 1.8 days, p = 0.02). Neither RYGB, gender, age nor BMI was associated with differential drinking patterns. Conclusion The results of this study suggest that some patients develop progressive AUD several years following RYGB. This observation has important clinical implications, calling for AUD-preventive measures following RYGB. Further large-scale longitudinal studies are needed to clarify the association between RYGB and AUD onset.

Chronic pain is a major public health concern, and widespread use of prescription opioids for chronic pain has contributed to the escalating problem of opioid use disorder. Interdisciplinary pain rehabilitation programs (IPRPs) can be highly effective in discontinuing opioids in patients with chronic pain while also improving functional status. This study sought to examine self-report and performance-based functional outcomes of 2 cohorts of patients enrolled in a 3-week IPRP: patients engaged in interdisciplinary pain treatment and physician-supervised opioid taper versus nonopioid users engaged in interdisciplinary treatment. Immediate and long-term treatment outcomes were assessed using a series of 2 (group: opioid use, no opioid use) × 2 (period: pretreatment, post-treatment) and 2 (group: opioid use, no opioid use) × 2 (period: pretreatment, 6 months post-treatment) mixed model analyses of variance. Group × Period interactions were nonsignificant whereas period effects were significant for all outcomes in directions indicating improvement (Ps .001) at discharge from the program and at 6 months, irrespective of opioid use status. Results support the assertion that IPRPs lead to significant improvements in subjective as well as objective indices of function, irrespective of opioid use status. Implications for our findings are discussed.This article provides support for the effectiveness of interdisciplinary, rehabilitative models of care in improving physical and emotional functioning of patients with chronic pain while simultaneously discontinuing opioid use. The reach of this work is substantial, because opioid dependency and chronic pain are public health problems in the United States.

Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.

Background and Objectives The aim of this study was to investigate potential gender differences in situations associated with heavy alcohol drinking. Methods Data from 395 alcohol dependent patients participating in the Mayo Clinic Intensive Addiction Program were evaluated. Each participant completed the inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS), patient health questionnaire (PHQ-9), and/or Beck depression inventory (BDI). Gender differences in IDTS scores representing three domains (negative, positive, and temptation) of situations associated with heavy alcohol use were examined. Results Women with alcohol dependence report a higher frequency of heavy drinking in unpleasant emotional (IDTS negative scores mean ± SD women vs. men: 52.3 ± 22.1 vs. 43.8 ± 21.8; p = .0006), and as a result of temptation (IDTS temptation scores mean ± SD women vs. men: 40.4 ± 23.0 vs. 35.3 ± 20.8; p = .035). Upon admission, women also scored significantly higher on depressive symptoms as measured by the BDI (23.4 ± 11.4 vs. 18.2 ± 9.8, p

The objectives of this study were to examine association between a family history of substance abuse and admission morphine equivalent dose, depression and pain catastrophizing screening scores, as well as reported personal history of substance use. The retrospective research was completed in an interdisciplinary three-week pain rehabilitation center. The subject cohort included admissions from January through December 2014 with 351 datasets for family history of substance abuse and oral morphine equivalency and 341 for depression, pain catastrophizing and use of substances. Outcome measures included admission self-reported data on family history of substance abuse and past and current substance use, admission morphine equivalency dose, and scores on the Center for Epidemiologic Studies-Depression Scale and the Pain Catastrophizing Scale. One hundred forty-seven patients were using opioid medications on admission and those with a positive family history of substance abuse had an oral morphine equivalency (M = 92.12, SD=95.32) compared to a negative history (M = 80.34, SD=64.86); the difference was not statistically significant, t (120.01) =.87, p = .39. Patients with a positive family history reported higher levels of both depression, t (327.40) = 3.15, p = .002 and pain catastrophizing, t (338) = 2.76, p = .01. Those with a positive family history endorsed greater frequency of past alcohol use χ 2 (1, N = 326) = 6.67, p = 0.1 and marijuana use χ 2 (1, N = 341) = 4.23, p = .04 and past χ 2 (1, N = 329) = 9.90, p = .002 and current tobacco use χ 2 (1, N = 327) = 8.81, p = .003. Use of family history of substance abuse information may help provide data for multimodal treatments of chronic non-cancer-pain. The findings from this study can be used to guide future research.

Background and Objectives: Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment. Methods: The study cohort included 314 alcohol-dependent subjects. Associations between relapse after discharge, PACS score, and clinical variables were investigated using time-to-event analyses. The primary analysis, based on the intent-to-treat principle, presumed relapse in those declining follow-up or not responding to contact attempts. Secondary analysis utilized data from 226 subjects successfully contacted after discharge with a median follow-up time of 365 days. Results: The intent-to-treat analysis demonstrated that relapse was associated with higher level of craving at admission (p= .002) and discharge (p < .001). The analysis of data from patients successfully contacted after discharge led to similar results. A multivariable analysis indicated that relapse rates increased as PACS scores increased, and a higher discharge PACS score was significantly associated with relapse (p= .006) even after adjusting for covariates. Conclusions and Scientific Significance: This study demonstrates that higher PACS scores at the time of admission and discharge are associated with relapse following residential addiction treatment. These data support the role of craving in relapse and the utility of craving measurement as a clinical guide in assessing relapse risk. (Am J Addict 2012;21:S20–S26)

To further explore reports of association of alcohol dependence and response to acamprosate treatment with the GATA4 rs13273672 single nucleotide polymorphism (SNP), we genotyped this and 10 other GATA4 SNPs in 816 alcohol-dependent cases and 1248 controls. We tested for association of alcohol dependence with the 11 SNPs individually and performed a global test for association using a principle components analysis. Our analyses demonstrate significant association between GATA4 and alcohol dependence at the gene level (P = 0.009) but no association with rs13273672. Further studies are needed to identify potential causal GATA4 variation(s) and the functional mechanism(s) contributing to this association.

Trazodone is one of the most commonly prescribed hypnotic medications in patients with sleep disturbances in alcohol recovery. A recent study concluded that treating insomnia with trazodone in patients with alcohol dependence might impede improvements in alcohol consumption and lead to increased drinking when trazodone is stopped. We set out to investigate the relationship between trazodone use during alcoholism treatment and relapse rates in patients who were discharged from a residential alcohol treatment program. We retrospectively reviewed records of patients with a diagnosis of alcohol dependence in a residential addiction treatment center from 2005 to 2008 and analyzed the association of trazodone use at discharge and alcohol relapse at 6 months. We also assessed the association between trazodone use and relapse at 6 months adjusting for sex, drug dependence, nonsubstance use Axis I psychiatric diagnoses, patient self-report of difficulties with sleep, and anti-dipsotropic medication use at discharge and evaluated pair-wise interactions of trazodone use with the adjustment variables. Of 283 patients eligible for inclusion, 85 (30%) were taking trazodone at discharge. Older age, self-reported sleep problems, and having a nonsubstance use Axis I psychiatric diagnosis were associated with trazodone use. After discharge, 170 (60%) subjects responded to follow-up efforts. Neither intent to treat nor responder only analysis revealed any association between trazodone use and relapse. Our retrospective study of a complex patient population discharged from a residential treatment setting did not find an association between trazodone use at discharge and relapse rates at 6 months.

Despite the high prevalence rate of comorbid alcohol dependence and bipolar disorder, little is known about how many bipolar patients are actively engaged in addiction treatment or the alcohol consumption characteristics of this group. This retrospective study reviewed the medical records from patients with alcohol dependence admitted to residential treatment at our institution (n = 588). The analyses focused on alcoholism severity measures and discharge clinical diagnoses. Patients with alcoholism + bipolar disorder compromised only 5% of the total study group. The number of drinking years was lower for patients with alcoholism + bipolar disorder (23.1 ± 17.7) than for those with alcoholism + depression (26.8 ± 13.9) or alcoholism alone (28.1 ± 13.2). A trend of higher mean lifetime maximum daily drinks was observed for patients with alcoholism + bipolar disorder; this was because of the significantly higher maximum drinks for women with bipolar disorder (21.0 ± 11.5) than for women in other diagnostic groups. Despite high rates of comorbidity in community-based studies, this retrospective study suggests that patients with bipolar disorder are not highly represented in residential alcoholism addiction treatment. Future studies are encouraged to better understand utilization rates of addiction treatment among patients with bipolar disorder and to identify clinical correlates that predispose bipolar women to high-dose drinking.

Background and Aims Depression and anxiety are often comorbid with alcoholism and contribute to craving and relapse. We aimed to estimate the prevalence of life-time diagnoses of major depressive disorder (MDD), substance-induced depression (SID), anxiety disorder (AnxD) and substance-induced anxiety (SIA), the effects of these comorbidities on the propensity to drink in negative emotional states (negative craving), and test whether these effects differ by sex. Design Secondary analyses of baseline data collected in a single-arm study of pharmacogenetic predictors of acamprosate response. Setting Academic medical center and affiliated community-based treatment programs in the American upper mid-west. Participants A total of 287 males and 156 females aged 18–80 years, meeting DSM-IV criteria for alcohol dependence. Measurements The primary outcome measure was ‘propensity to drink in negative emotional situations’ (determined by the Inventory of Drug Taking Situations) and the key predictors/covariates were sex and psychiatric comorbidities, including MDD, SID, AnxD and SIA (determined by Psychiatric Research Interview of Substance and Mood Disorders). Findings The prevalence of the MDD, SID and AnxD was higher in females compared with males (33.1 versus 18.4%, 44.8 versus 26.4% and 42.2 versus 27.4%, respectively; P

BackgroundPsychiatric comorbidities and alcohol craving are known contributors to differences in alcohol consumption patterns.MethodsUnivariate and multivariable linear regression models were used to examine the association and interactions between the Inventory of Drug Taking Situations (IDTS) negative, positive and temptation sub-scale scores, sex, as well as co-morbid depression and anxiety determined by Psychiatric Research Interview of Substance and Mood Disorders (PRISM) with alcohol consumption measured by Time Line Follow Back (TLFB) during preceding 90 days in 287 males and 156 females meeting DSM-IV criteria for alcohol dependence.ResultsIDTS positive, negative and temptation scores were strongly associated with increased alcohol consumption measures including the number of drinks per day and number of drinking days per week (P < 0.0001). Male sex was associated with higher amount of alcohol consumption per drinking day (P < 0.001), but not with the number of drinking days per week (P > 0.05). In men, lifetime history of depression was associated with fewer drinking days (P = 0.0084) and fewer hazardous drinking days (P = 0.0214) but not with differences in daily alcohol consumption. In women, depression history was not significantly associated with alcohol consumption measures. Post-hoc sex-stratified analyses suggested that the association of the negative IDTS score with total amount of alcohol consumed by men may be modified (decreased) by lifetime depression history. We found no associations of alcohol consumption measures with anxiety or substance-induced depression.DiscussionDecreased frequency of drinking in male alcoholics with lifetime depression history is unexpected. This finding emphasizes the complex relationships between alcoholism and depression, which require further investigation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Acamprosate supports abstinence in some alcohol-dependent subjects, yet predictors of response are unknown. To identify response biomarkers, we investigated associations of abstinence length with polymorphisms in candidate genes in glycine and glutamate neurotransmission pathways and genes previously implicated in acamprosate response. Association analyses were conducted in the discovery sample of 225 alcohol-dependent subjects treated with acamprosate for 3 months in community-based treatment programs in the United States. Data from 110 alcohol-dependent males treated with acamprosate in the study PREDICT were used for replication of the top association findings. Statistical models were adjusted for relevant covariates, including recruitment site and baseline clinical variables associated with response. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for covariates, length of abstinence was associated with the GRIN2B rs2058878 (P = 4.6 x 10(-5)). In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P = 0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P = 0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics. Investigation of the underlying mechanisms of this association and its usefulness for individualized treatment selection should follow.

Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment.The study cohort included 314 alcohol-dependent subjects. Associations between relapse after discharge, PACS score, and clinical variables were investigated using time-to-event analyses. The primary analysis, based on the intent-to-treat principle, presumed relapse in those declining follow-up or not responding to contact attempts. Secondary analysis utilized data from 226 subjects successfully contacted after discharge with a median follow-up time of 365 days.The intent-to-treat analysis demonstrated that relapse was associated with higher level of craving at admission (p= .002) and discharge (p.001). The analysis of data from patients successfully contacted after discharge led to similar results. A multivariable analysis indicated that relapse rates increased as PACS scores increased, and a higher discharge PACS score was significantly associated with relapse (p= .006) even after adjusting for covariates.This study demonstrates that higher PACS scores at the time of admission and discharge are associated with relapse following residential addiction treatment. These data support the role of craving in relapse and the utility of craving measurement as a clinical guide in assessing relapse risk.

Background Heavy alcohol use is causally associated with liver dysfunction. Prior genome wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) associated with liver cirrhosis or elevation of liver enzymes (including aspartate aminotransferase or AST and alanine aminotransferase or ALT) in alcohol dependent subjects. Yet, it is possible that effects of SNPs on liver function may depend on the extent of recent alcohol exposure, which was not investigated in these studies. To address this gap in our knowledge, we investigated SNP-by-consumption interaction effects on the levels of three liver enzymes (AST, ALT and gamma-glutamyl transferase or GGT) commonly used in clinical practice to assess liver function in alcohol dependent subjects Methods Self-reported alcohol consumption during previous 30 days (measured by Timeline Follow back), DNA and plasma samples for measurement of AST, ALT and GGT levels were collected from 480 alcohol dependent subjects treated in community-based treatment programs. Genotyping was conducted using Illumina HumanCore array. Multivariable linear regression models were used to assess the effects of SNP-by-consumption interaction on ALT, AST and GGT levels. Results Genome-wide significant evidence of consumption-interaction effects on AST (p Discussion Genomic location of our top association findings indicates their potential involvement in the essential cellular function, which may also be relevant for alcohol-related liver damage. Specifically, EXOSC10 gene is a putative catalytic component of the RNA exosome complex involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA as well as elimination of RNA processing by-products. Moreover, the top SNP in ALT analysis (EXOSC10 rs2258621) might be a blood eQTL for MTOR, which is a serine/threonine protein kinase, belonging to a family of kinases mediating cellular responses to stresses such as DNA damage and nutrient deprivation. Similarly, GALNT2 encodes protein involved in metabolism and O-linked glycosylation pathways, while PDE9A encodes protein involved in signal transduction by regulating the intracellular concentration of cAMP and cGMP. Replication in the independent sample as well as investigation of the functional mechanisms behind these associations needs to follow.

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

Trazodone is one of the most commonly prescribed hypnotic medications in patients with sleep disturbances in alcohol recovery. A recent study concluded that treating insomnia with trazodone in patients with alcohol dependence might impede improvements in alcohol consumption and lead to increased drinking when trazodone is stopped. We set out to investigate the relationship between trazodone use during alcoholism treatment and relapse rates in patients who were discharged from a residential alcohol treatment program. We retrospectively reviewed records of patients with a diagnosis of alcohol dependence in a residential addiction treatment center from 2005 to 2008 and analyzed the association of trazodone use at discharge and alcohol relapse at 6 months. We also assessed the association between trazodone use and relapse at 6 months adjusting for sex, drug dependence, nonsubstance use Axis I psychiatric diagnoses, patient self-report of difficulties with sleep, and anti-dipsotropic medication use at discharge and evaluated pair-wise interactions of trazodone use with the adjustment variables. Of 283 patients eligible for inclusion, 85 (30%) were taking trazodone at discharge. Older age, self-reported sleep problems, and having a nonsubstance use Axis I psychiatric diagnosis were associated with trazodone use. After discharge, 170 (60%) subjects responded to follow-up efforts. Neither intent to treat nor responder only analysis revealed any association between trazodone use and relapse. Our retrospective study of a complex patient population discharged from a residential treatment setting did not find an association between trazodone use at discharge and relapse rates at 6 months.

Despite the high prevalence rate of comorbid alcohol dependence and bipolar disorder, little is known about how many bipolar patients are actively engaged in addiction treatment or the alcohol consumption characteristics of this group. This retrospective study reviewed the medical records from patients with alcohol dependence admitted to residential treatment at our institution (n = 588). The analyses focused on alcoholism severity measures and discharge clinical diagnoses. Patients with alcoholism + bipolar disorder compromised only 5% of the total study group. The number of drinking years was lower for patients with alcoholism + bipolar disorder (23.1 ± 17.7) than for those with alcoholism + depression (26.8 ± 13.9) or alcoholism alone (28.1 ± 13.2). A trend of higher mean lifetime maximum daily drinks was observed for patients with alcoholism + bipolar disorder; this was because of the significantly higher maximum drinks for women with bipolar disorder (21.0 ± 11.5) than for women in other diagnostic groups. Despite high rates of comorbidity in community-based studies, this retrospective study suggests that patients with bipolar disorder are not highly represented in residential alcoholism addiction treatment. Future studies are encouraged to better understand utilization rates of addiction treatment among patients with bipolar disorder and to identify clinical correlates that predispose bipolar women to high-dose drinking.

This study examines the clinical correlates of alcohol craving in men and women self-referred for addiction treatment. Admission clinical data from patients participating in the Mayo Clinic 1-month Intensive Addictions Program were evaluated. Women had higher BDI and PACS scores compared with men in both the entire cohort and Dual Diagnoses group. Alcohol-dependent females had the most marked correlation between BDI and PACS (rho= .78). Further prospective study is encouraged to evaluate whether depressive symptoms and concomitant alcohol cravings in women are a marker for relief cravings and, as such, a target symptom for treatment intervention.

Introduction. We have previously demonstrated an association of PDYN rs2281285 and haplotypes including this variant with alcohol dependence, negative craving and propensity to drink to avoid alcohol withdrawal (Karpyak et al. 2013; Preuss et al. 2013). We re-analyzed our data to examine sex-related associations of PDYN variation with alcohol dependence and related phenotypes. Methods. 13 PDYN …

Introduction Recent findings support sex-specific effects of PDYN polymorphisms on association with opioid addiction (Clarke et al. 2012). We have demonstrated that PDYN haplotypes, which include rs2281285, are associated with alcohol dependence and propensity to drink in negative emotional situations (negative craving) (Karpyak et al 2012). The rs2281285 variant may contribute to regulation of alternative PDYN mRNA transcription specific to brain area or physiological condition. Objectives To investigate sex-specific effects of the PDYN rs2281285 variant on risk for alcohol dependence. Aims To examine the association of the PDYN rs2281285 variant with alcohol dependence in male and female subjects. Methods rs2281285 was genotyped in the investigation cohort of 816 (554 males) alcohol dependent subjects (DSM-IV-TR) and 1248 (603 males) non-alcoholic controls and in the replication cohort of 467 (347 males) alcohol dependent subjects and 431 (224 males) non-alcoholic controls. Logistic regression models were used to test for sex-specific associations after controlling for age. Results As previously reported, significant association of the PDYN rs2281285 variant with alcohol dependence was found in the investigation (p = 0.008, odds ratio = 1.299), but not the replication cohort (0.223, OR = 0.118). However, sex-specific analyses revealed stronger association in males (p = 0.002, OR = 1.493) but not females (p = 0.684, OR = 1.066) in the investigation cohort, and a trend for association in males (p = 0.086, OR = 1.352) but not females (p = 0.808, OR = 0.947) in the replication cohort. Conclusions Our findings support association of PDYN rs2281285 variant with alcohol dependence in male but not female subjects. Future studies should investigate functional mechanisms of this effect.

Introduction Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence. Objectives To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence. Aims Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes. Methods 13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender. Results Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p Conclusions Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.