ALDH2 Deficiency Promotes Alcohol-Associated Liver Cancer by Activating Oncogenic Pathways via Oxidized DNA Enriched Extracellular Vesicles

Significance: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that detoxifies the alcohol metabolite acetaldehyde in the liver. This study demonstrated that ALDH2-deficient mice or humans with chronic liver disease and high alcohol consumption are more susceptible to liver cancer, due to increased production of oxidized mitochondrial DNA-enriched extracellular vesicles that activate multiple oncogenic pathways. Thus, inhibition of oxidized mitochondrial DNA-enriched extracellular vesicle production could be a novel therapeutic strategy for ameliorating alcohol-associated liver cancer in ALDH2-deficient individuals.

Background & Aims: Excessive alcohol drinking is one of the major causes of hepatocellular carcinoma (HCC). Approximately 30-40% Asian population are deficient for aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify the ethanol metabolite acetaldehyde. However, how ALDH2 deficiency affects alcohol-related HCC remains obscure. Methods: ALDH2 polymorphism in 646 patients with viral hepatitis B (HBV) infection with or without alcohol drinking was studied. A new model of HCC induced by chronic carbon tetrachloride (CCl4) and alcohol administration was developed and studied in three lines of Aldh2-deficient mice: including Aldh2 global knockout (KO) mice, Aldh2*1/*2 knock-in mutant mice, and liver-specific Aldh2 KO mice. Results: We demonstrated that ALDH2 deficiency was not associated with liver disease progression but was associated with an increased risk of HCC development in cirrhotic HBV patients with excessive alcohol consumption. The mechanisms underlying HCC development associated with cirrhosis and alcohol consumption were studied in Aldh2-deficient mice. We found that all three lines of Aldh2-deficient mice were more susceptible to CCl4 plus alcohol-associated liver fibrosis and HCC development. Furthermore, our results from in vivo and in vitro mechanistic studies revealed that after CCl4 plus ethanol exposure, Aldh2-deficient hepatocytes produced a large amount of harmful oxidized mtDNA via extracellular vesicles (EVs), which were then transferred into neighboring HCC cells and together with acetaldehyde activated multiple oncogenic pathways (JNK, STAT3, BCL-2, and TAZ), thereby promoting HCC. Conclusions: ALDH2 deficiency is associated with an increased risk of alcohol related-HCC development from fibrosis in patients and in mice. Mechanistic studies reveal a novel mechanism that Aldh2-deficient hepatocytes promote alcohol-associated HCC by transferring harmful oxidized mtDNA-enriched EVs into HCC and subsequently activating multiple oncogenic pathways in HCC. (Seo W, Gao Y, He Y, Sun J, Xu H, Feng D, Hee Park S, Cho YE, Guillot A, Ren T, Wu R, Wang J, Kim SJ, Hwang S, Liangpunsakul S, Yang Y, Niu J, and Gao B. J Hepatol. 2019 Jul 4. pii: S0168-8278(19)30390-3)

Targeting Peripheral CB1 Receptors Reduces Ethanol Intake via a Gut-Brain Axis

 Significance: Endocannabinoids and ghrelin are both implicated in promoting alcohol intake, but interactions between the two systems have not been characterized. This study demonstrated that cannabinoid-1 receptor (CB1R) signaling in ghrelin-producing stomach cells modulates the formation of biologically active ghrelin, which then activates a gut-brain signaling pathway that leads to increased alcohol consumption. Peripherally-restricted pharmacological inhibition of CB1R, which avoids the psychiatric side effects of blocking CB1R in the central nervous system, reduced ethanol drinking in mice. Thus, peripheral CB1 receptor blockade may have therapeutic potential in the treatment of alcoholism.

 Endocannabinoids acting on the cannabinoid-1 receptor (CB1R) or ghrelin acting on its receptor (GHS-R1A) both promote alcohol-seeking behavior, but an interaction between the two signaling systems has not been explored. Here, we report that the peripheral CB1R inverse agonist JD5037 reduces ethanol drinking in wild-type mice but not in mice lacking CB1R, ghrelin peptide or GHS-R1A. JD5037 treatment of alcohol-drinking mice inhibits the formation of biologically active octanoyl-ghrelin without affecting its inactive precursor desacyl-ghrelin. In ghrelin-producing stomach cells, JD5037 reduced the level of the substrate octanoyl-carnitine generated from palmitoyl-carnitine by increasing fatty acid β-oxidation. Blocking gastric vagal afferents abrogated the ability of either CB1R or GHS-R1A blockade to reduce ethanol drinking. We conclude that blocking CB1R in ghrelin-producing cells reduces alcohol drinking by inhibiting the formation of active ghrelin and its signaling via gastric vagal afferents. Thus, peripheral CB1R blockade may have therapeutic potential in the treatment of alcoholism. (Godlewski G, Cinar R, Coffey NJ, Liu J, Jourdan T, Mukhopadhyay B, Chedester L, Liu Z, Osei-Hyiaman D, Iyer MR, Park JK, Smith RG, Iwakura H, and Kunos G. Cell Metab. 2019 Jun 4;29(6):1320-1333.e8)

Maternal Circulating miRNAs That Predict Infant FASD Outcomes Influence Placental Maturation

Significance: Previous research identified 11 miRNAs in the plasma of pregnant women that predict infant fetal alcohol spectrum disorders (FASD) outcomes following prenatal alcohol exposure (Balaraman S. et al., 2016). In the current report, the same team demonstrated in a mouse model that these miRNAs restrict placental maturation by inhibiting trophoblast epithelial-mesenchymal transition, a key process for development of the placenta. Importantly, in-vitro cell data also supported the potential of targeting these miRNAs for therapeutic intervention. Collectively, these findings suggest that prenatal alcohol results in fetal growth restriction in part by impairing placental function via specific miRNAs.

Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction. (Tseng AM*, Mahnke AH, Wells AB, Salem NA, Allan AM, Roberts VH, Newman N, Walter NA, Kroenke CD, Grant KA, Akison LK, Moritz KM, Chambers CD, and Miranda RC; Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Life Sci Alliance. 2019 Mar 4;2(2). pii: e201800252)

*Denotes NIAAA-funded F trainee

 Activation of Glycine Receptors in the Lateral Habenula Rescues Anxiety- and Depression-Like Behaviors Associated with Alcohol Withdrawal and Reduces Alcohol Intake in Rats

Significance: The negative emotional state associated with alcohol withdrawal is a driving force for alcohol relapse; however, the underlying neurobiological mechanisms are not fully understood. In this study, activation of glycine receptors in the lateral habenula alleviated alcohol withdrawal-induced anxiety- and depression-like behaviors and reduced alcohol consumption in rats. These data, together with recent evidence on the critical role of the lateral habenula in depression, reveal a new mechanism underlying the negative emotional state associated with alcohol withdrawal and a potential therapeutic target for alcohol use disorder.

The lateral habenula (LHb) is activated by a range of aversive states including those related to alcohol withdrawal and has glycine receptors (GlyRs), a sensitive target of alcohol. However, whether GlyRs in the LHb contribute to alcohol-related behaviors is unknown. Here, we report that rats experiencing withdrawal from chronic alcohol consumption showed higher anxiety and sensitivity to stress compared to their alcohol-naïve counterparts. Intra-LHb injection of glycine attenuated these aberrant behaviors and reduced alcohol intake upon alcohol re-access. Glycine's effect was blocked by strychnine, a GlyR antagonist, indicating that it was mediated by strychnine-sensitive GlyRs. Conversely, intra-LHb strychnine elicited anxiety- and depression-like behaviors in Naïve rats but not in withdrawal rats. Additionally, both the frequency and the amplitude of the spontaneous IPSCs were lower in LHb neurons in slices of withdrawal rats compared to naïve rats. Also, there were sporadic strychnine-sensitive synaptic events in some LHb neurons. Bath perfusion of strychnine induced a depolarizing inward current and increased action potential firings in LHb neurons. By contrast, bath perfusion of glycine or sarcosine, a glycine transporter subtype 1 inhibitor, inhibited LHb activity. Collectively, these data reveal that LHb neurons are under the tonic glycine inhibition both in physiological and pathological conditions. Activation of GlyRs reverses LHb hyperactivity, alleviates aberrant behaviors, and reduces alcohol intake, thus highlighting the GlyRs in the LHb as a potential therapeutic target for alcohol-use disorders. (Li W, Zuo W, Wu W, Zuo QK, Fu R, Wu L, Zhang H, Ndukwe M, and Ye JH. Neuropharmacology. 2019 Oct; 157:107688)

Stroop-Related Cerebellar and Temporal Activation is Correlated with Negative Affect and Alcohol Use Disorder Severity

Significance: This study used functional brain imaging to study the relationships between cognitive control, the severity of alcohol use disorder (AUD), and measures of negative affect such as anxiety and depression. There was greater activation in the cerebellum and temporal cortex during a cognitive interference task that was correlated with a greater degree of AUD severity and more reported negative affect. Activation in the cerebellum was still associated with negative affect after controlling for the effects of drinking history and AUD severity. These results suggest that the cerebellum may play a more prominent role in negative affect and AUD than previously realized and provides a potential target for intervention.

 Impairment in cognitive control in alcohol use disorder (AUD) contributes to difficulty controlling alcohol use and, in many populations, difficulties with emotion regulation. However, the most reliable and robust marker of clinically-relevant deficits in cognitive control in AUD is unclear. Our aims were to measure relationships between BOLD signal during a Stroop task and AUD severity and change in BOLD signal and change in drinking over three weeks. We also aimed to explore the relationships between BOLD signal and subjective negative affect. Thirty-three individuals with AUD underwent a multisensory Stroop task during functional magnetic resonance imaging (fMRI), as well as a battery of neuropsychological tests and self-report assessments of negative affect and AUD severity. Greater activation in temporal gyrus and cerebellum during incongruent trials compared to congruent trials was observed, and percent signal change (incongruent minus congruent) in both clusters was positively correlated with AUD severity and self-reported negative affect. Neuropsychological task performance and self-reported impulsivity were not highly correlated with AUD severity. Hierarchical regression analyses indicated that percent signal change (incongruent minus congruent) in cerebellum was independently associated with negative affect after controlling for recent and chronic drinking. In a subset of individuals (n = 23) reduction in cerebellar percent signal change (incongruent minus congruent) was correlated with increases in percent days abstinent over 3 weeks. BOLD activation during this Stroop task may therefore be an important objective marker of AUD severity and negative affect. The potential importance of the cerebellum in emotion regulation and AUD severity is highlighted.  (Wilcox CE*, Clifford J, Ling J, Mayer AR, Bigelow R, Bogenschutz MP, and Tonigan JS. Brain Imaging and Behavior 2019 May 22. doi: 10.1007/s11682-019-00126-3)

*Denotes NIAAA-funded K awardee

 Sex Differences in Trait Anxiety’s Association with Alcohol Problems in Emerging Adults: The Influence of Symptoms of Depression and Borderline Personality

Significance: Lifetime alcohol drinking is often associated with anxiety, depression, and other mental health conditions such as borderline personality disorder (BPD). However, the extent to which sex differences contribute to these conditions in relation to drinking problems is not well understood. This study assessed trait anxiety, depression, and symptoms of BPD in a large sample of young adults (ages 18—30) with varying lifetime alcohol-related problems. The results showed that the correlation between trait anxiety and alcohol problems was significantly stronger in men than women, regardless of depression and BPD symptoms. These findings suggest sex-specific mechanisms underlying the relationship between trait anxiety and alcohol problems.

Objective: The co-occurrence of alcohol use disorder (AUD) and internalizing psychopathology, such as anxiety and depression, has been well documented. However, most studies of the association between alcohol problems and anxiety, do not simultaneously consider depression or borderline personality, which covary strongly with both anxiety symptoms and AUDs. The current study examined sex differences in the association between alcohol problems and anxiety, while accounting for depressive and borderline personality (BPD) symptoms. Method: A sample 810 (364 females) young adults aged 18–30 recruited from the community, who varied widely in lifetime alcohol problems, were administered diagnostic interviews and measures of a trait anxiety, depression, and BPD symptoms. Results: Analyses revealed that trait anxiety, depression, and borderline symptoms were all significantly associated with higher lifetime alcohol problems in both males and females. However, the association between trait anxiety and alcohol problems was significantly stronger for males compared with females, even when controlling for depression and BPD symptoms. There were no significant sex differences in the association between alcohol problems and symptoms of either depression or BPD symptoms. Conclusion: This suggests specific sex differences in the mechanisms by which trait anxiety is associated with alcohol problems. (Atkinson EA and Finn PR.  Journal of Substance Use. 2019. 24:3, 323-328. doi: 10.1080/14659891.2019.1572800)

Intravenous Administration of Ghrelin Increases Serum Cortisol and Aldosterone Concentrations in Heavy-Drinking Alcohol-Dependent Individuals: Results from a Double-Blind, Placebo-Controlled Human Laboratory Study

Significance: Effects of ghrelin administration on cortisol and aldosterone, two corticosteroid hormones involved in the neurobiology of alcohol use disorder (AUD), have been observed in previous studies. In this study, serum concentrations of cortisol and aldosterone were used to develop a model to predict the effect of ghrelin administration on alcohol craving in individuals with AUD. Intravenous ghrelin administration increased endogenous levels of cortisol and aldosterone; only the ghrelin-induced changes in aldosterone serum concentrations predicted craving. These findings provide initial evidence of a link between ghrelin and corticosteroids in the context of AUD, thereby providing additional information on how the ghrelin system may play a role in alcohol-related behaviors.

Increasing evidence supports the role of appetite-regulating hormones, including ghrelin, in alcohol use disorder (AUD). Effects of ghrelin administration on cortisol and aldosterone, two hormones known to influence the development and maintenance of AUD, have been observed in ghrelin-exposed tissues or cells, as well as rodents and healthy volunteers, however whether these effects replicate in individuals with AUD is unknown. Here, we tested the hypothesis that intravenous administration of ghrelin leads to increase in endogenous serum cortisol and aldosterone concentrations in alcohol-dependent, heavy drinking individuals, and that these changes may predict ghrelin-induced alcohol craving. This was a double-blind, placebo-controlled human laboratory study in non-treatment-seeking, heavy-drinking, alcohol-dependent individuals randomized to receive either placebo, 1 mcg/kg or 3 mcg/kg of intravenous ghrelin. Then, participants underwent a cue-reactivity procedure in a bar-like setting, which included exposure to both neutral (juice) and alcohol cues. Repeated blood samples were collected and used to measure endogenous cortisol and aldosterone serum concentrations, in response to exogenous ghrelin administration. Furthermore, cortisol and aldosterone serum concentrations were used to develop a model to predict the effect of exogenous ghrelin administration on alcohol craving. Intravenous ghrelin administration increased endogenous cortisol and aldosterone serum concentrations. While the effects on cortisol were greater than those on aldosterone, only the ghrelin-induced changes in aldosterone serum concentrations predicted craving. These findings provide initial evidence of ghrelin effects on glucocorticoids and mineralocorticoids in individuals with AUD, thereby providing additional information on the potential mechanisms by which the ghrelin system may play a role in alcohol craving and seeking in AUD. (Haass-Koffler CL, Long VM, Farokhnia M, Magill M, Kenna GA, Swift RM, and Leggio L. Neuropharmacology. 2019 Jul 13:107711. doi: 10.1016/j.neuropharm.2019.107711)

Alcohol Rehabilitation Within 30 Days of Hospital Discharge Is Associated With Reduced Readmission, Relapse, and Death in Patients With Alcoholic Hepatitis

Significance: Patients who have recovered from alcoholic hepatitis (AH) remain at risk of readmission and death, outcomes generally attributed to alcohol relapse. This analysis of two different patient cohorts evaluated 30-day rates of hospital readmission, alcohol relapse, and long-term mortality in AH patients. In both cohorts, participation in early alcohol rehabilitation (within 30 days of discharge from AH treatment) was associated with decreased 30-day readmission, decreased 30-day alcohol relapse, and importantly, decreased mortality. These results suggest that all patients with AH should be formally evaluated by addiction specialists during their hospital stay and referred for treatment within 30 days of hospital discharge.

BACKGROUND & AIMS: Patients admitted to the hospital for alcoholic hepatitis (AH) are at increased risk of readmission and death. We aimed to identify factors associated with readmission, alcohol relapse, and mortality. METHODS: We performed a retrospective analysis of consecutive patients admitted with AH to a tertiary care hospital from 1999 through 2016 (test cohort, n = 135). We validated our findings in a prospective analysis of patients in a multi-center AH research consortium from 2013 through 2017 (validation cohort, n = 159). Alcohol relapse was defined as any amount of alcohol consumption within 30 days after hospital discharge. Early alcohol rehabilitation was defined as residential or outpatient addiction treatment or mutual support group participation within 30 days after hospital discharge. RESULTS: Thirty-day readmission rates were 30% in both cohorts. Alcohol relapse rates were 37% in the test and 34% in the validation cohort. Following hospital discharge, 27 patients (20%) in the test cohort and 19 patients (16%) in the validation cohort attended early alcohol rehabilitation. There were 53 deaths (39%) in a median follow-up time of 2.8 years and 42 deaths (26%) in a median follow-up time of 1.3 years, respectively. In the test cohort, early alcohol rehabilitation reduced odds for 30-day readmission (adjusted odds ratios [AOR] 0.16; 95% CI, 0.04-0.65; P = .01), 30-day alcohol relapse (AOR, 0.11; 95% CI, 0.02-0.53; P < .001), and death (adjusted hazard ratio [AHR], 0.20; 95% CI, 0.05-0.56; P = .001). In the validation cohort early alcohol rehabilitation reduced odds for 30-day readmission (AOR, 0.30; 95% CI, 0.09-0.98; P = .04), 30-day alcohol relapse (AOR 0.09; 95% CI, 0.01-0.73; P = .02), and death (AHR, 0.20; 95% CI, 0.01-0.94; P = .04). A model combining alcohol rehabilitation and bilirubin identified patients with readmission to the hospital within 30 days with an area under the receiver operating characteristic curve of 0.73. CONCLUSIONS: In an analysis from two cohorts of patients admitted with AH, early alcohol rehabilitation can reduce risk of hospital readmission, alcohol relapse, and death and should be considered as a quality indicator in AH hospitalization treatment. (Peeraphatdit TB, Kamath PS, Karpyak VM, Davis B, Desai V, Liangpunsakul S, Sanyal A, Chalasani N, Shah VH, and Simonetto DA. Clin Gastroenterol Hepatol. 2019 Apr 28. pii: S1542-3565(19)30438-0)

Health Care Use Over 3 Years After Adolescent SBIRT

Significance: Research suggests that screening, brief intervention, and referral to treatment (SBIRT) in pediatric primary care may improve patient outcomes, but few studies have examined its effects on health care use or the development of medical or mental health comorbidities over time. This study used electronic health data to examine subsequent health care use among adolescents from a randomized clinical trial comparing usual care to two modalities of delivering SBIRT in pediatric primary care (either pediatrician- or behavioral clinician-delivered). Results indicated that patients with access to SBIRT had fewer comorbidities, fewer psychiatry visits at 1 year, and fewer substance use diagnoses, as well as lower outpatient use over 3 years. These findings suggest that providing SBIRT in primary care may reduce health care use and improve adolescent health.

BACKGROUND: Most studies on adolescent screening, brief intervention, and referral to treatment (SBIRT) have examined substance use outcomes. However, it may also impact service use and comorbidity-an understudied topic. We address this gap by examining effects of SBIRT on health care use and comorbidities. METHODS: In a randomized trial sample, we assessed 3 SBIRT care modalities: (1) pediatrician-delivered, (2) behavioral clinician-delivered, and (3) usual. Medical comorbidity and health care use were compared between a brief-intervention group with access to SBIRT for behavioral health (combined pediatrician and behavioral clinician arms) and a group without (usual care) over 1 and 3 years. RESULTS: Among a sample of eligible adolescents (n = 1871), the SBIRT group had fewer psychiatry visits at 1 year (incidence rate ratio [iRR] = 0.76; P = .05) and 3 years (iRR = 0.65; P < .05). Total outpatient visits did not differ in year 1. The SBIRT group was less likely to have mental health diagnoses (odds ratio [OR] = 0.69; 95% confidence interval [CI] = 0.48-1.01) or chronic conditions (OR = 0.66; 95% CI = 0.45-0.98) at 1 year compared with those in usual care. At 3 years, the SBIRT group had fewer total outpatient visits (iRR = 0.85; P < .05) and was less likely to have substance use diagnoses (OR = 0.64; 95% CI = 0.45-0.91) and more likely to have substance use treatment visits (iRR = 2.04; P < .01). CONCLUSIONS: Providing SBIRT in pediatric primary care may improve health care use and health, mental health, and substance use outcomes. We recommend further exploring the effects of SBIRT on these outcomes. (Sterling S, Kline-Simon AH, Jones A, Hartman L, Saba K, Weisner C, and Parthasarathy S. Pediatrics. 2019 May;143(5). pii: e20182803. doi: 10.1542/peds.2018-2803)

The Relationship Between the U.S. State Alcohol Policy Environment and Individuals' Experience of Secondhand Effects: Alcohol Harms Due to Others' Drinking

Significance: “Secondhand effects” of alcohol refer to harms resulting from others’ drinking. This study examined the prevalence of alcohol’s secondhand effects and whether the prevalence of these effects differed based on the strength of a state’s policies (expressed as an Alcohol Policy Scale value). Secondhand harms in three categories – aggression-related, family- or financial-related, and driving-related – were experienced by 16.8 percent of people under age 40 and 7.8 percent of people over age 40. For those under 40, state policies known to reduce binge drinking and impaired driving were linked to lower levels of reported aggression-related harms and drunk driving-related harms. These findings demonstrate that many people suffer consequences from alcohol use by others and suggest that state policies known to reduce binge drinking and impaired driving might also reduce the secondhand harms of alcohol, particularly among individuals under 40.

BACKGROUND: Although restrictive state alcohol policy environments are protective for individuals' binge drinking, research is sparse on the effect of alcohol policies on alcohol's harms to others (AHTO). We examined the lagged associations between efficacy of U.S. state alcohol policies and number of harms from others' drinking 1 year later. METHODS: Individuals with AHTO data in a nationally representative sample of U.S. adults (analytic sample n = 26,744) that pooled the 2000, 2005, 2010, and 2015 National Alcohol Surveys and a 2015 National Alcohol's Harm to Others Survey were linked with prior-year state policy measures. We used 2 measures from the Alcohol Policy Scale (APS)-effectiveness in reducing (i) binge drinking and (ii) impaired driving, based on experts' efficacy judgments regarding 29 state alcohol policies. Three 12-month AHTO measures (due to another drinker) were experiencing: (i) either family/marriage difficulties or financial troubles; (ii) being assaulted or vandalized; and (iii) passenger with drunk driver or traffic accident. Multilevel models accounting for clustering within states and stratified by age-groups (<40 vs. ≥40) examined associations between the APS and AHTO measures, controlling for individual covariates (gender, race, education, employment and marital status, family problem-drinking history) of the victim. RESULTS: Only for those aged <40, the lagged APS-Binge drinking and APS-Impaired driving scores were each inversely associated with aggression-related harms and, separately, with drunk driving-related harm from someone else's drinking (ps < 0.05 to < 0.01). Family/financial harms were not associated with APS scores for either age-group. Composite AHTO measures (any of 3 harm-types) also were inversely associated with stronger state alcohol policy environments (ps < 0.05 to <0.01). CONCLUSIONS: State alcohol policies may be effective in reducing, to a meaningful degree, aggression-related harms and vehicular hazards due to other drinkers, but mainly in those under 40. (Greenfield TK, Cook WK, Karriker-Jaffe KJ, Patterson D, Kerr WC, Xuan Z, and Naimi TS. Alcohol Clin Exp Res. 2019 Jun;43(6):1234-1243. doi: 10.1111/acer.14054)

NIAAA COMMUNICATIONS ACTIVITIES

Press and Publications Activities: 

Recent News Media Interviews:  Dr. Koob continues to speak with a variety of national and international news outlets on timely topics related to NIAAA’s research and its impact on treatment and prevention of alcohol misuse and AUD. Notable interviews by Dr. Koob and other staff since April 2019 include New York Times, Boston Globe, CNN en Español, The Guardian, NPR, Philadelphia Inquirer, and The Washington Post.

Press Releases:

• Dr. Carlo C. DiClemente to Deliver 11^th Annual Jack Mendelson Honorary Lecture at the National Institutes of Health (July 9, 2019)
• Integrated stepped alcohol treatment for people in HIV care improves both HIV and alcohol outcomes (May 17, 2019)
• NIAAA Honors Dr. Geoffrey K. Mumford with Senator Harold Hughes Award (May 14, 2019)

 Please see the News and Events section of the NIAAA website for this and other news releases. 

Publication Statistics: In the month of July 2019, NIAAA filled orders for 15,181 copies of print publications. As of July 17, 2019, there were 30,045 Granicus/GovDelivery listserv subscribers to Alcohol Research: Current Reviews; 23,779 to the NIAAA Spectrum; 893 to News Alerts; and 22,877 to receive general information. 

Social Media Highlights:

• In recent months, NIAAA has been spotlighting summer students in its ongoing #NIAAAtraining series, which focuses on training opportunities and the experience of trainees at the institute. 


• Summer safety has also been featured on social media, with messages about the risks of mixing alcohol with swimming and boating, the increased risk of sunburn while drinking, and the dangers of dehydration from alcohol.

• NIAAA continues to use social media to promote the Alcohol Treatment Navigator and recently released a new animation about the resource. NIAAA’s social media audience is growing steadily with 23,600 Twitter followers and 800 followers on its Instagram account.

Partnerships, Outreach and Public Liaison Activities: 

Summer Safety Outreach

NIAAA disseminated its fact sheet titled “Risky Drinking Can Put a Chill on Your Summer Fun” to the media through PR Newswire’s US1 distribution with AP photo release on June 6 and July 3, 2019. The fact sheet was posted by Internet news outlets such as The Daily Meal, WBBH-TV, One News Page, News Blaze, The Street, KWTV-TV, and Buffalo News as well as business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. The release had a total of 164 unique links, representing a total potential audience of 71 million people. The fact sheet graphic also appeared on Cision’s Times Square billboard a total of 21 times on June 6, and 11 times on July 3, 2019. In addition to the PR Newswire releases, four Cision email blasts were distributed on May 29, June 12 and 25, and July 10 to a total of 17,360 TV and print reporters. Health News Digest, Lansing State Journal, News-Star.com, and NewKerala.com ran related articles after receiving the Cision emails.

Overdose Fact Sheet – A focused and targeted summer promotion of the NIAAA fact sheet titled “Alcohol Overdose: The Dangers of Drinking Too Much” resulted in a 174 percent increase in pageviews compared to the same period in 2018.

High School Graduation – The NIAAA fact sheet titled “Parents—Talk With Your High School Grads About Celebrating Safely” was disseminated to the media through PR Newswire on US1 distribution with AP photo release on May 13 and May 15, 2019. The fact sheet was posted by Internet news outlets such as Ask.com, Sun Coast News Network, Rockford Register Star, Washington, DC CityRoom, as well as blogs, business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. The release had a total of 147 unique links, representing a total potential audience of 49 million people. The fact sheet graphic also appeared on Cision’s Times Square billboard a total of 10 times on May 13, 2019, and five times on May 15, 2019. In addition to the PR Newswire releases, a Cision email blast was sent to more than 2,100 local and national TV and print reporters on May 20. NBC29.com, CBS19.com, Motherhood Moment, News-Star.com, and NewKerala.com ran related stories from information in the Cision email.

Back to College – The NIAAA fact sheet titled “Fall Semester–A Time for Parents to Discuss the Risks of College Drinking” was disseminated to the media through Cision/PR Newswire’s US1 distribution with AP photo release on August 13 and 19. Pickup is being monitored.

Select Partnership Updates 

• NABCA Webinar: During Alcohol Awareness Month, Dr. Aaron White presented a webinar on April 10 with the National Alcohol Beverage Control Association (NABCA). The title was “Changes in Alcohol Use in the US – ED Visits and Other Outcomes.” The presentation is available at https://youtu.be/yA-pPJr2aW0.
  
  
  
  
   
• SADD: During National Prevention Week, May 13—17, in partnership with NIAAA, the group Students Against Destructive Decisions (SADD) issued a video challenge, calling on student members to submit brief videos with messages that counter misconceptions about alcohol and addressed students’ concerns about alcohol misuse. More than 30 student entries were received. Selected participating SADD organizations were awarded a stipend from NIAAA to attend SADD’s National Conference on June 23-25. SADD showcased the videos on its social media platform and at multiple conference events.


• CADCA: On July 17, Dr. Ralph Hingson presented at the Community Anti-Drug Coalitions of America (CADCA) Mid-Year Training Institute. He spoke on “New Research Since the Surgeon General's Call to Action to Prevent and Reduce Underage Drinking.”

Special Events 

• Hughes Award: On May 14, NIAAA presented the Senator Harold Hughes Memorial Award to Dr. Geoffrey K. Mumford, Associate Executive Director for Government Relations in the Science Directorate of the American Psychological Association (APA). The Hughes Award recognizes the contributions of an individual whose work translates research into practice, and builds bridges across the alcohol prevention, treatment and policy-making communities. The award is named for Harold Hughes, a former Iowa Governor and U.S. Senator, who was a major force behind the 1970 legislation that led to the creation of NIAAA.
• Mendelson Lecture: On July 11, 2019, Dr. Carlo C. DiClemente, Professor Emeritus, Department of Psychology, University of Maryland, Baltimore County, presented the 11th Annual Mendelson Lecture, “Is Relapse and Recycling Necessary for Recovery from Alcohol Use Disorder?” NIAAA established the lecture series as a tribute to Dr. Jack Mendelson, who made remarkable contributions to the field of clinical alcohol research. A video recording of Dr. DiClemente’s lecture is available at https://videocast.nih.gov/summary.asp?live=33218&bhcp=1.

Web Activities

• The Communication and Public Liaison Branch (CPLB) Launches New Customer Satisfaction Survey: CPLB’s web team added a new customer satisfaction survey to the NIAAA Main website and the online Alcohol Treatment Navigator. CPLB has collected more than 2,000 responses for NIAAA Main (4 weeks’ worth of data). These measures will provide useful data on what our web visitors are looking for and how we can improve our sites.
• Grantees Offer Feedback on NIAAA Website: As part of a long-term redesign project, CPLB reached out to NIAAA grantees for feedback about our website (what they use it for and how we can improve it). Dozens of grantees responded. This feedback will help CPLB’s web team determine continued improvements in web content, organization, and design during our Drupal 8 software migration.
• CPLB Implements Web Upgrades: in recent months CPLB has—
  • Enhanced many of NIAAA’s popular web publications, brochures, and fact sheets by improving usability through responsive designs tailored to mobile devices.
  • Redesigned the publications web order form onto NIAAA’s main web platform. (See https://www.niaaa.nih.gov/niaaa-publications-order-form)
  • Implemented responsive design and other search engine optimization (SEO) methods.