Alcoholic Research Articles

The eyes have it: Alcohol-induced eye movement impairment and perceived impairment in older adults with and without alcohol use disorder.

While alcohol has been shown to impair eye movements in young adults, little is known about alcohol-induced oculomotor impairment in older adults with longer histories of alcohol use. Here, we examined whether older adults with chronic alcohol use disorder (AUD) exhibit more acute tolerance than age-matched light drinkers (LD), evidenced by less alcohol-induced oculomotor impairment and perceived impairment. Two random-order, double-blinded laboratory sessions with administration of alcohol (0.8 g/kg) or placebo. Participants (n = 117; 55 AUD, 62 LD) were 40-65 years of age. Eye tracking outcomes (pupil size, smooth pursuit gain, pro- and anti-saccadic velocity, latency, and accuracy) were measured at baseline and repeated at peak and declining breath alcohol intervals. Participants rated their perceived impairment during rising and declining intervals. Following alcohol consumption, older adults with AUD (vs. LD) showed less impairment on smooth pursuit gain and reported lower perceived impairment, but both groups showed similar pupil dilation and impairment on saccadic measures. While alcohol impaired older adults with AUD less than LD in terms of their ability to track a predictably moving object (i.e., smooth pursuit), both drinking groups were equally sensitive to alcohol-induced delays in reaction time, reductions in velocity, and deficits in accuracy to randomly appearing objects (i.e., saccade tasks). Thus, despite decades of chronic excessive drinking, older adults with AUD exhibited similar oculomotor tolerance on pro- and anti-saccade eye movements relative to their light-drinking counterparts. Given that these individuals also perceived less impairment during intoxication, they may be at risk for injury and harm when they engage in real-life drinking bouts.

Correlates of length of stay in a short-term inpatient residential addiction treatment facility.

There is a gap in the extant literature regarding length of stay (LOS) in short-term inpatient addiction treatment facilities. Furthermore, there is a lack in focus on treatment factors which may be better indicators for positive patient outcomes than demographic profiles. The current study sought to examine modifiable correlates of LOS within a short-term inpatient residential facility to extend LOS and improve patient outcomes. N = 792 participants who completed a baseline assessment and either completed treatment or left against clinical advice were included in the sample. Outcomes of interest were self-efficacy (domains included negative affect, pro-social or positive use, physical discomfort, withdrawal, or urges), well-being (domains included symptom distress, interpersonal relations, and social role), and social network size. Baseline dysfunctional social role, larger social network size, and higher alcohol use disorder (AUD) severity all led to increases in LOS. No aspects of self-efficacy, symptom distress, interpersonal relatedness, substance use disorder (SUD) severity, nor other demographic variables were associated with LOS. This study highlights the importance of taking steps to improve self-perceived social role and social network size. Given that the purpose of this study was to determine modifiable correlates of LOS, we suggest that clinicians at inpatient, short-term addiction treatment centers adopt thorough measures of well-being and social network to support patient treatment and recovery.

Perspectives and experiences regarding pre-exposure prophylaxis (PrEP) in a community sample of Veterans with unhealthy alcohol use: overall and across sexual orientation and gender identity

BackgroundUnhealthy alcohol use is an independent, modifiable risk factor for HIV, but limited research addresses alcohol use and HIV prevention synergistically. Groups that experience chronic stigma, discrimination, and/or other marginalization, such as sexual and gender minoritized groups, may have enhanced HIV risk related to unhealthy alcohol use. We described awareness of and experiences with pre-exposure prophylaxis (PrEP) among a community sample of Veterans reporting unhealthy alcohol use (relative to those without), overall and across self-reported sexual orientation and gender identity.MethodsUsing data collected from a national online survey of Veterans recruited via Facebook ads, community organizations, and listservs, we assessed variation in four PrEP outcomes (knowledge, experience, willingness, and conversations with doctors) across patterns of unhealthy alcohol use among all respondents reporting any lifetime drinking (n = 1,041) and then within sexual orientation and gender identity groups using Chi-square or Fisher’s exact tests.ResultsAmong 1,041 eligible Veterans, 440 (42%) screened positive for unhealthy alcohol use. Veterans with unhealthy alcohol use were not more likely to have heard of PrEP (58.2% vs. 55.4%, p = 0.37), but trended toward more likely to have taken PrEP (7.5% vs. 5.0%, p = 0.09), to be willing to take PrEP (30.5% vs. 27.6%, p = 0.06), and to have spoken with a doctor about PrEP (11.4% vs. 7.7%, p = 0.04). Those with heavy episodic drinking also trended toward higher prevalence of PrEP awareness (60.0% vs. 54.6%, p = 0.09), and were more likely to have taken PrEP (8.3% vs. 4.7%, p = 0.02), to be willing to use PrEP (34.6% vs. 25.5%, p < 0.01), and to have had conversations with doctors about PrEP (12.7% vs. 7.2%, p < 0.01). Similar patterns were observed for severe unhealthy alcohol use and past-year frequent heavy episodic drinking. Generally, sexual/gender minoritized Veterans with unhealthy alcohol use reported more PrEP-affirming responses than those without but associations with unhealthy alcohol use were similar.ConclusionsUnhealthy alcohol use was prevalent, particularly among Veterans with minoritized sexual orientation/gender identity, but not clearly linked to increased PrEP-literacy and use despite its known status as an HIV risk factor. Across groups, > 25% of individuals were willing to take PrEP. Interventions targeting both alcohol use and HIV prevention should capitalize on this.

Recovery support services as part of the continuum of care for alcohol or drug use disorders.

The definition of 'recovery' has evolved beyond merely control of problem substance use to include other aspects of health and wellbeing (known as 'recovery capital') which are important to prevent relapse to problematic alcohol or other drug (AOD) use. Developing a Recovery Oriented System of Care (ROSC) requires consideration of interventions or services (Recovery Support Services, RSS) designed to build recovery capital which are often delivered alongside established treatment structures. Lived experience and its application to the process of engaging people, changing behaviour and relapse prevention is an essential part of these services. To map out the evidence base for RSS as part of guidance for commissioners of addiction services in each of the 152 local authorities in England. The authors updated the findings of a 2017 systematic review of RSS through a further rapid scoping review, aiming to map out the extent, range and nature of research under six headings: (1) Peer-based recovery support services (P-BRSS); (2) Employment support approaches; (3) Recovery housing; (4) Continuing care and recovery check-ups; (5) Recovery community centres (RCC); and (6) Recovery support services in educational settings. A systematic search of the PubMed, Embase, CINAHL, CENTRAL and PsychINFO databases was conducted. The abstracts of all articles published since 2017 were reviewed by two of the authors, and the full text versions of all relevant articles were obtained and relevant data extracted. A narrative review of the findings was then prepared, mapping them on to the ROSC continuum of care. The review was restricted to adults (over 18 years), but all substances and available outcomes were included. Four of the six forms of RSS were well supported by evidence. RCTs of interventions to increase levels of employment demonstrated large effect sizes, and continuing care interventions that extend treatment intervention into the early recovery phase have shown small but significant benefit. Peer-delivered interventions to link people to ongoing support were associated with decreased rates of relapse and re-admission, increased engagement, and increased social support for change. However, the variability in the design of these studies means that further work is required to clarify the effective components of the intervention. Studies of recovery housing have also shown positive results, including significant differences from standard care. No controlled studies exist to support RCCs or RSS in educational settings, but the complexity of these interventions and the wide range of potential outcome measures mean that other study designs may be more relevant. This monograph provides a structure to help policy makers, commissioners and service providers describe and understand an emerging field of research. Recovery Support Services (RSS) are proving to have clinical, public health and cost utility. A rational social and fiscal response to endemic alcohol or other drug challenges should therefore include the more intensive acute care clinical services linked with more extensive community-based RSS.

Rethinking gender differences: An investigation of comorbid psychopathology and alcohol use disorder in veterans.

While men have been found to drink more alcohol and have higher rates of alcohol-related mortality, women tend to experience higher rates of alcohol-related consequences, including psychological comorbidities and worse alcohol use disorder (AUD) outcomes. However, gender differences in comorbid psychopathology and associations with AUD outcomes among veterans are less well understood. Veterans (N = 126; 32 women) receiving inpatient treatment for AUD completed baseline clinical measures including the Beck Depression Inventory-II, Beck Anxiety Inventory, Early Life Stress Questionnaire, and PTSD Checklist for DSM-5. Alcohol use was assessed with the Timeline Followback for the 90 days prior to the baseline assessment and again at 1-, 3-, and 6-month follow-ups. Gender differences in baseline alcohol and psychopathology measures were examined using Fisher's exact test and Mann-Whitney U test. Linear/logistic regression was used to examine associations between comorbid psychopathology and alcohol relapse/use severity post-study. Consistent with prior literature, statistically significant gender differences in psychopathology were observed, with women reporting higher anxiety (p < 0.001), depression (p = 0.001), early life stress (p < 0.001), and PTSD (p < 0.001) at baseline. Higher early life stress was also associated with higher anxiety, depression, and PTSD. Statistically significant gender differences were not observed for alcohol use in the 90 days prior to the study. Similarly, gender was not associated with relapse or severity of use at 1-, 3-, or 6-month follow ups (ps > 0.05). Psychopathology measures were not associated with relapse or severity of use at any time point (ps > 0.05). Our study highlights that women veterans are drinking similar quantities of alcohol to men, supporting emerging evidence of a narrowing gender gap in alcohol use. Women also have a higher psychiatric burden than men; thus, identifying ways to mitigate comorbidity among women veterans should be a health priority.

Comparing Outcomes and Infection Risk in Medical, Surgical, and Trauma Intensive Care Patients with Alcohol Use Disorder.

Introduction: Alcohol is the most frequently abused drug in the United States, and alcohol use disorder (AUD) is a common comorbidity in intensive care units (ICUs). Patients and Methods: We performed a retrospective chart review of patients admitted to an ICU between January 2017 and March 2019 at a tertiary hospital serving a large rural population. Patients with diagnoses of AUDs were included. Patients were excluded if they did not require ICU care. Patient demographics, hospital course, infection type, culture results, and mortality were evaluated. We compared medical, surgical, and trauma ICU patient outcomes and infections. Results: In total, 527 patients met inclusion and exclusion criteria. Trauma ICU patients had the least pre-existing comorbidities, and surgical ICU patients had the longest lengths of stay. There was no difference in in-hospital mortality between ICU groups; however, surgical and medical ICU patients had significantly greater rates of in-hospital mortality compared with trauma ICU patients. Infections were common across all ICU types, occurring in 40% of patients. There was no difference in infection rate between ICU types. In multi-variable analysis controlling for age, gender, liver failure, chronic kidney disease, thrombocytopenia, complications, and blood transfusions, infection remained an independent predictor of in-hospital mortality (adjusted odds ratio 3.3, 95% confidence interval 1.7-6.4). Septic shock occurred in 57% of infections and was associated with an increased risk of mortality (38% vs. 2%, p < 0.001). Pneumonia was the most common infection occurring in 28% of the cohort, followed by bacteremia (7%), skin/soft tissue infections (6%), urinary tract infection (5%), intra-abdominal infections (4%), and C. difficile (2%). Conclusions: AUDs in all types of ICU patients are associated with high rates of infections and high morbidity and mortality.

Substance Use Classes Among YMSM in an HIV Digital Health Intervention Program: Implications for Acceptability, Engagement, and Health Outcomes.

Young men who have sex with men (YMSM) have high rates of substance use, which increases their risk for HIV. Digital Health Interventions (DHI) have the potential to address HIV risk overall and reduce harms in the context of substance use. However, there is limited research on how YMSM with different substance use patterns respond to HIV DHIs and how these programs impact participant outcomes. In this study, we used latent class analysis (LCA) to identify subgroups of participants with specific substance use behaviors in the Keep It Up! (KIU! ) program, an HIV DHI with prior documented effectiveness. This study involved 2,124 participants in a Type III Hybrid trial, comparing two implementation strategies: one via 22 community-based organizations and another through direct-to-consumer recruitment. Evaluations were done at baseline and 12-week follow-up. This analysis identified four classes of substance use: Low Use (minimal alcohol risks, low illicit drug use, infrequent marijuana), Heavy Use (highest alcohol problems, frequent marijuana, elevated illicit drug use), Alcohol and Marijuana Use (high alcohol problems, frequent marijuana), and Methamphetamine and GBH Use (low alcohol risk, moderate marijuana frequency, high illicit drug use). Participants in the Meth & GHB User class were more likely to have an STI at baseline compared to those in the Low User class. Moreover, Heavy Use, Alcohol & Marijuana Use, and Meth & GHB Use reported a greater number of condomless anal sex partners compared to Low Use. Additionally, although Alcohol & Marijuana Use were more likely to use PrEP at the time of their most recent casual partner at baseline, they exhibited the smallest increase in PrEP use during follow-up compared to the other substance use classes. Our analysis did not unveil substantial differences in the success of implementation in terms of reach, suggesting that both implementation strategies effectively engaged YMSM with different levels of substance use. Our research showed a similar level of engagement, as evidenced by the completion rates of modules and time spent, across all substance use classes. However, those within the Meth & GHB category found the intervention highly acceptable, but less so compared to Low Use and Alcohol & Marijuana Use. Understanding how distinct substance use profiles influence intervention outcomes and exploring varied implementation methods can augment future prevention endeavors, broadening the scope and impact of public health initiatives.

EXPLORATORY STRUCTURAL NEUROIMAGING EXAMINATION OF IMPULSIVITY IN SEVERE ALCOHOL USE DISORDER: PERSISTENT IMPLICATION OF THE VENTRAL STRIATUM.

While Alcohol Use Disorder (AUD) is frequently associated with impulsivity, its structural brain substrates are still poorly defined. The triadic model of addiction postulates that impulsive behavior is regulated by an amygdalo-striatal impulsive subcomponent, a prefrontal and cerebellar reflective subcomponent, and an insular regulatory subcomponent. The objective of this study was thus to examine the relationships between self-evaluated impulsivity and structural brain abnormalities in patients with severe AUD (sAUD) using the triadic model as a theoretical framework. Twenty-two inpatients with sAUD and 17 Healthy Controls (HC) completed two impulsivity scales: the Barratt Impulsiveness Scale-11 (BIS-11), and the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency Impulsive Behavior Scale (UPPS). They also underwent an anatomical MRI. The brain volumes of the regions described as involved in the three subcomponents of the triadic model were extracted. The two groups did not significantly differ on self-reported impulsivity measures. However, the volumes of the caudate nuclei, executive cerebellum and insula were smaller in sAUD than in HC. In the sAUD group there were significant positive correlations between certain impulsivity measures and gray matter volume of the nucleus accumbens. In sAUD, self-evaluated impulsivity specifically relates to the integrity of the ventral striatum that belongs to the impulsive subcomponent of the triadic neurocognitive model of addiction. It is not related to the integrity or deterioration of the brain regions that underlie the reflexive or regulatory sub-component. Although these results have methodological limitations, they are consistent with the impulsive/compulsive model of addiction and confirms the persistence of the relationship between impulsivity and ventral striatum in sAUD.

Facilitators and Barriers Associated With Mental Health Service Utilization Among Individuals With Alcohol Use Disorder in Korea

Objective The treatment rate for alcohol use disorder (AUD) in Korea is significantly lower than its prevalence rate. Because untreated AUD can have harmful consequences, it is important to identify the factors that contribute to individuals with AUD seeking mental health services.Methods We collected nationally representative data from the National Mental Health Survey of Korea 2021 and analyzed responses from 643 individuals with AUD, of which 76.8% were male. Factors related to mental health service utilization among individuals with AUD were classified into three categories: sociodemographic (such as sex, age, marital status, education, and monthly household income), clinical (including symptom severity, psychiatric comorbidity, suicidality, and physical illness), and psychological characteristics (like perceived stigma, loneliness and social isolation, and resilience). We used multiple logistic regression analyses to examine each characteristic separately and combined in a single model to determine the most significant factors.Results The three logistic regression models revealed that sex, psychiatric comorbidity, physical illness, and perceived stigma are significantly linked to the utilization of mental health services among individuals with AUD. Results from the comprehensive model indicated that only physical illness and perceived stigma have significant associations with mental health service utilization.Conclusion These findings can assist in developing targeted interventions for individuals with AUD.

Culturally informed risk perceptions among young adult drinkers in Denmark, Estonia and Italy

Alcohol researchers have debated whether increased globalisation has reduced national differences in alcohol consumption and thus made alcohol cultures more similar. Building on this interest, this article examines the cultural perceptions of alcohol risk among young adult drinkers in Denmark, Estonia and Italy to find out if important cultural differences still exist in Europe. The study is based on 24 focus groups (n = 128) in the three countries with people aged 20–30 and 30–40. Our study shows how each of the three countries had different narratives about risk and drinking. Estonian participants described how heavy drinking could lead to neglecting one’s responsibilities as an adult, which could result in a loss of social status. Italian participants’ alcohol risk assessments were more related to the value of togetherness and social community and the embarrassment that could be felt if this was compromised. Danish participants mentioned few alcohol-related risks and these were primarily linked to the individual and not, as among the Italian and Estonian participants, to the social group or family. The findings of the study are analysed and discussed in the light of overall cultural narratives in each of the three countries and we conclude that alcohol cultures and everyday risk assessments of alcohol may be changing but only slowly.

Neural cue reactivity and intrinsic functional connectivity in individuals with alcohol use disorder following treatment with topiramate or naltrexone.

Both topiramate and naltrexone have been shown to affect neural alcohol cue reactivity in alcohol use disorder (AUD). However, their comparative effects on alcohol cue reactivity are unknown. Moreover, while naltrexone has been found to normalize hyperactive localized network connectivity implicated in AUD, no studies have examined the effect of topiramate on intrinsic functional connectivity or compared functional connectivity between these two widely used medications. This study compared topiramate versus naltrexone on alcohol cue-elicited brain activation and intrinsic functional connectivity in patients with alcohol use disorder. Forty-seven participants with alcohol use disorder received daily topiramate (titrating the dose up to 200mg/day n = 21) or naltrexone (50mg/day, n = 26) for at least 6 weeks. Using functional magnetic resonance imaging (fMRI), we examined intrinsic functional connectivity during rest and alcohol cue-elicited neural activation during a visual alcohol cue reactivity task 120min following treatment administration. Functional connectivity and alcohol cue reactivity and percentage of heavy drinking days (% HDD) associations were assessed. No differences in either intrinsic functional connectivity or alcohol cue-elicited neural activity were seen between topiramate and naltrexone-treated groups. Overall, participants showed increased alcohol cue-elicited activation in three clusters spanning occipital regions involved in visual recognition of stimuli, and hypoactivation to both alcohol and control cues in three clusters involved in salience attribution and processing of emotional valence of external stimuli. No differences between topiramate versus naltrexone were observed for either functional measure or associations with post-scan % HDD. Topiramate and naltrexone enacted comparable alcohol cue reactivity and intrinsic functional connectivity patterns. Some overall responses of increased brain activation to alcohol cues in visual processing regions coupled with reduced activation to alcohol and control cues were evidenced for both treatments. These activation patterns were in regions expected to show attenuation of brain activity resulting from treatment. Topiramate and naltrexone may thus enact functional effects through similar modulation of functional neural activity in individuals with AUD. ClinicalTrials.gov, NCT03479086 https://www. gov/study/NCT03479086 .

Comparative Analysis of Blood MMP-9 Concentration in Alcohol- and Opioid-Addicted Patients

Background/Objectives: In brain physiology and disease, MMP-9 is a significant and apparently peculiar factor. Numerous studies have implicated neuroinflammatory processes involving MMP-9 in the pathophysiology of addiction. This study aims to evaluate plasma MMP-9 level as a biomarker for the stages of alcohol and opioid addiction. Methods: The case subjects were patients with opioid and alcohol addiction. The quantitative assessment of MMP-9 plasma concentration was performed using monoclonal antibodies against human MMP-9. Results: MMP-9 levels in the plasma of patients with alcohol and opioid dependence differ from MMP-9 concentrations in apparently healthy donors. During the intoxication stage, MMP-9 concentrations in individuals with alcohol and opioid dependence are similar and higher than in the control group. While the MMP-9 level is close to the control level after alcohol withdrawal, it stays increased during opioid withdrawal. When MMP-9 levels in plasma were measured in three distinct intoxicated states (light, moderate, and heavy) in cases of alcohol addiction, the results were all similar. Two distinct opioid intoxicated states (methadone and buprenorphine) and three withdrawals—following methadone, buprenorphine, and heroin abuse—were associated with high MMP-9 levels.

WOOP as a Brief Alcohol Intervention Led by Lay Coaches in College Settings.

Heavy drinking is a major public health concern, particularly among young adults who often experience fear of being stigmatized when seeking help for alcohol-related problems. To address drinking concerns outside clinical settings, we tested the feasibility of a novel imagery-based behavior change strategy led by student lay interventionists in a college setting. Participants were adults recruited on a college campus and were randomized to either learn the four steps of WOOP (Wish, Outcome, Obstacle, and Plan) or to learn a format-matched Sham WOOP (Wish, Outcome, "Outcome," and Plan). Both WOOP and Sham WOOP interventions were taught by student lay interventionist. We found that the WOOP intervention group reported fewer heavy drinking days (≥ 5 drinks for men or ≥ 4 drinks for women, measured using the Alcohol Timeline Follow-Back Method) compared to the Sham group at the 1-month and 2-month follow-ups. WOOP, when taught by student lay interventionists in a single session, demonstrated the feasibility of reducing heavy drinking. WOOP shows promise as a low-cost and scalable intervention for reducing heavy drinking in nonclinical settings.

Blood Catalase, Superoxide Dismutase, and Glutathione Peroxidase Activities in Alcohol- and Opioid-Addicted Patients

Background and Objectives: Multiple evaluations of oxidative stress in individuals with substance use disorder show elevated levels compared to non-substance-abusing individuals. Information concerning antioxidant defense mechanisms in relation to alcohol and opioid dependence is variable and sometimes contradictory. The objective of the present investigation was to identify and compare several antioxidants in plasma during distinct phases of alcohol and opioid dependency (intoxication and withdrawal). Materials and Methods: This case study focuses on individuals with opioid and alcohol addiction. We recruited 80 participants (males aged 40 ± 10 years) and equally divided them into two categories: those with alcohol addiction and those with opioid addiction. A control group consisted of 20 healthy adults (males aged 35 ± 10 years). The spectrophotometric methods were used to quantify catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity in plasma. Antioxidant values were analyzed between groups using pairwise Mann–Whitney tests. Results: During withdrawal from alcohol and opioids, catalase activity tends to decrease compared to intoxication. The overall activity of superoxide dismutase exhibited an increase during alcohol intoxication and withdrawal and a reduction during opioid withdrawal compared to the intoxication phase. Both alcohol and opioids reduced plasma GPx activity in withdrawal cases, although the extent of this decrease varied considerably. Conclusions: The study confirms the valuable impact of addiction on the organism’s oxidative stress and reveals various behaviors of antioxidant defense enzymes during intoxication and withdrawal phases.

In Silico Pharmacogenomic Assessment of Glucagon-like Peptide-1 (GLP1) Agonists and the Genetic Addiction Risk Score (GARS) Related Pathways: Implications for Suicide Ideation and Substance Use Disorder.

Glucagon-Like Peptide-1 Receptor (GLP1R) agonists have become widespread anti-obesity/diabetes pharmaceuticals in the United States. This article aimed to provide our current knowledge on the plausible mechanisms linked to the role of Ozempic (Semaglutide), which is generalized as one of the anti-addiction compounds. The effects of GLP1R agonists in Alcohol Use Disorder (AUD) and substance use disorder (SUD) are mediated, in part, through the downregulation of dopamine signaling. We posit that while GLP1R agonism could offer therapeutic advantages in hyperdopaminergia, it may be detrimental in patients with hypodopaminergia, potentially leading to long-term induction of Suicidal Ideation (SI). The alleged posit of GLP1 agonists to induce dopamine homeostasis is incorrect. This study refined 31 genes based on the targets of Ozempic, GLP1R, and related enzymes for SI and 10 genes of the Genetic Addiction Risk Score (GARS) test. STRING-MODEL refined 29 genes, and further primary analyses indicated associations of GLP1R with DRD3, BDNF, CREB1, CRH, IL6, and DPP4. In-depth silico enrichment analysis revealed an association between candidate genes and depressive phenotypes linked with dopaminergic signaling. Finally, through primary and in-depth silico analyses, we demonstrated multiple findings supporting that GLP1R agonists can induce depression phenotypes. Our findings suggest that associated polymorphisms seem to have overlapping effects with addictive behaviors of Reward Deficiency Syndrome (RDS) and dopamine regulation. Consequently, GLP1R agonists may represent a double-edged sword, potentially triggering both antiaddictive effects and SI by exacerbating depressive phenotypes. Thus, we encourage the scientific community to perform further empirical clinical studies to confirm this proposed pathway.

Evaluating sex and line differences in successive negative contrast and ethanol consumption using alcohol preferring and high alcohol drinking rats.

The loss of a job or relationship are a couple of examples of unexpected reward loss. Life events, such as these can induce negative emotional reactions (e.g., anxiety and stress), which have been associated with increased alcohol consumption and in turn, an increased risk of developing an alcohol use disorder (AUD). The present study analyzed consummatory successive negative contrast (SNC) for the first time in alcohol preferring (P) and high alcohol drinking (HAD) rats that have been selectively bred to consume high amounts of ethanol. Following reward loss, animals were given free access to ethanol to determine whether consumption would increase as a possible indication of any negative emotional reaction. Male and female P and HAD rats were split into shifted and unshifted groups receiving either 32% or 4% sucrose for 5 min across 10 preshift days. Subsequently, all animals received 4% sucrose for four postshift days, across which, animals were given access to 20% ethanol for 30 min after access to 4% sucrose. Male and female P rats demonstrated a longer contrast effect than HAD rats, indicated by a longer recovery time following the downshift in reward. Conversely, HAD males did not demonstrate a contrast effect following this downshift in reward unlike their female counterparts. Surprisingly, P rats who experienced a loss of reward consumed significantly less ethanol than animals who did not. Lastly, individual measure of contrast size, or shift ratio, was significantly associated with greater ethanol consumption in HAD males only, who did not display a contrast effect. These data indicate different reactivity to SNC between these two lines and sexes, suggesting different genetic and sex-related mechanisms underlying sensitivity to an unexpected loss of reward and ethanol consumption following this loss.

Post-discharge complications and follow-up timing after hospitalization for traumatic rib fractures.

To evaluate frequency and timing of post-discharge complications in patients with traumatic rib fractures undergoing operative or nonoperative management. We retrospectively reviewed adult patients with rib fractures admitted to a Level 1 trauma center from 1/2020 to 12/2021. Outcomes included rib-related complications, pneumonia within 1 month, new diagnosis of opioid- or alcohol-use disorder, and all-cause mortality. Patients were stratified on whether they underwent surgical stabilization of rib fractures (SSRF). Associations between risk factors and outcomes were evaluated through Fine and Gray hazard models with death (or in-hospital death for the post-discharge death outcome) as a competing risk. Of 976 patients admitted with rib fractures, 904(93%) underwent non-operative therapy and 72(7%) underwent SSRF. Nonoperative patients had less-severe injuries and shorter ICU length-of-stay. Rib-related complications occurred in 13(1%) nonsurgical patients and 4(6%) surgical patients. In the nonsurgical group, presence of hemo/pneumothorax on admission was associated with increased risk of rib-related complications [subdistribution hazard ratio (SHR) (95% CI): 5.95(1.8, 19.67)]. Pneumonia within 1 month occurred in 9(1%) nonsurgical patients and 1(1%) surgical patient. New diagnosis of alcohol or opioid-use disorder was made in 14(2%) nonsurgical patients and 1(1%) surgical patients. All-cause mortality was 68(8%) in the nonsurgical group and 2(3%) in the surgical group. Older age was associated with mortality in the nonsurgical cohort [SHR (95% CI): 1.83(1.46, 2.28)]. Post-discharge rib-related complications were rare in both groups, but occurred primarily within 2 weeks, suggesting concentrated earlier follow-up may be beneficial. These findings help inform recommendations for follow-up in this population.

The Association Between Childhood Experience of Living with a Heavy Drinker and Self-Rated Mental Health in the Adult General Population

Background and Objectives: Considering the link between childhood experiences with adult health and well-being, this study examined how living with a heavy drinker (HD) during childhood affected self-rated mental health (SRMH) in adulthood, while identifying risk and protective factors and assessing the prevalence within a regional context. Materials and Methods: Data (N = 11,113) were obtained from a cross-sectional DEEP SEAS survey (2021) of the general population, aged 18–64 years, in six countries (Croatia, Bosnia and Herzegovina, Slovenia, Austria, Hungary, and Italy). Results: A statistically significant difference in SRMH was found, related to the childhood experience of living with an HD (MD = −0.221, 95% CI −0.250–0.172, N = 10,886) and being negatively affected (MD = −0.216, 95% CI −0.311–0.122, N = 2978). The correlation analysis revealed that individuals who lived with an HD during childhood perceived poorer SRMH in adulthood, consistently across all observed countries. Subsequent logistic regression identified different predictors for SRMH between those who were negatively affected and those who were not. The relationship satisfaction (RAS) was the strongest predictor, significantly contributing to better SRMH, especially in the subgroup that was not negatively affected (OR 28.724, 95% CI 3.450–239.173). A high prevalence of individuals negatively affected was found, especially in Hungary (34.4%) and Croatia (26.5%). Conclusions: Growing up with someone who was a heavy drinker may have lasting negative consequences on SRMH, with a negative subjective evaluation of mental health in adulthood. Targeted public health and preventive measures are needed to protect those living with heavy drinkers.

Distinct sex differences in ethanol consumption and operant self-administration in C57BL/6J mice with uniform regulation by glutamate AMPAR activity

IntroductionConsidering sex as a biological variable (SABV) in preclinical research can enhance understanding of the neurobiology of alcohol use disorder (AUD). However, the behavioral and neural mechanisms underlying sex-specific differences remain unclear. This study aims to elucidate SABV in ethanol (EtOH) consumption by evaluating its reinforcing effects and regulation by glutamate AMPA receptor activity in male and female mice.MethodsC57BL/6J mice (male and female) were assessed for EtOH intake under continuous and limited access conditions in the home cage. Acute sensitivity to EtOH sedation and blood clearance were evaluated as potential modifying factors. Motivation to consume EtOH was measured using operant self-administration procedures. Sex-specific differences in neural regulation of EtOH reinforcement were examined by testing the effects of a glutamate AMPA receptor antagonist on operant EtOH self-administration.ResultsFemale C57BL/6J mice exhibited a time-dependent escalation in EtOH intake under both continuous and limited access conditions. They were less sensitive to EtOH sedation and had lower blood levels post-EtOH administration (4 g/kg) despite similar clearance rates. Females also showed increased operant EtOH self-administration and progressive ratio performance over a 30-day baseline period compared to males. The AMPAR antagonist GYKI 52466 (0–10 mg/kg, IP) dose-dependently reduced EtOH-reinforced lever pressing in both sexes, with no differences in potency or efficacy.DiscussionThese findings confirm that female C57BL/6J mice consume more EtOH than males in home-cage conditions and exhibit reduced acute sedation, potentially contributing to higher EtOH intake. Females demonstrated increased operant EtOH self-administration and motivation, indicating higher reinforcing efficacy. The lack of sex differences in the relative effects of GYKI 52466 suggests that AMPAR activity is equally required for EtOH reinforcement in both sexes.

A Quantitative and Qualitative Analysis of the Patient and Caregiver’s Perspective on Outcomes of Intravenous Administration of Low-Dose Ketamine for C-PTSD, TBI, and Treatment Resistant MDD: A Clinical Example

Background and Clinical Significance: Treatment resistant psychiatric disorders affect millions of people across the globe. Ketamine has been employed as a treatment option for those with treatment resistant depression, as well as for chronic pain and alcohol use disorder. However, case presentations and research has been limited on the outcomes, and furthermore there is even less on the patient or caregiver perspective on the impact of the treatment. Case Presentation: Here, we present a middle-aged male who has undergone 20 intravenous (IV) ketamine infusions to treat Complex Post-Traumatic Stress Disorder (C-PTSD) and Major Depressive Disorder (MDD). We provide both qualitative perspectives from the patient, caregiver, as well as quantitative analyses of the patient from the Patient Health Questionnaire-9 (PHQ9), Beck’s Depression Inventory (BDI), and the Neurobehavioral Symptom Inventory (NSI) following treatment and weekly (4 weeks) assessments between treatments. Conclusions: Collectively, these data provide a holistic view of the use of ketamine for this patient on a variety of mental health, physiological, and behavioral conditions.