bluuebunny/crossref_metadata_2025_split huggingface dataset:
fMRI BOLD Response to the Eyes Task in Offspring From Multiplex Alcohol Dependence Families
Authors: Hill Shirley Y. , Kostelnik Bryan , Holmes Brian , Goradia Dhruman , McDermott Michael , Diwadkar Vaibhav , Keshavan Matcheri 
Published: November 2007

Background:  Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain.Methods:  Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron‐Cohen during functional magnetic resonance imaging (fMRI).Results:  High‐risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low‐risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks.Conclusions:  Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others’ state of mind, possibly resulting in diminished social skill.
Rates and Correlates of Relapse Among Individuals in Remission From DSM‐IV Alcohol Dependence: A 3‐Year Follow‐Up
Authors: Dawson Deborah A. , Goldstein Risë B. , Grant Bridget F. 
Published: November 2007

Background:  There is little information on the stability of abstinent and nonabstinent remission from alcohol dependence in the general U.S. population. The aim of this study was to examine longitudinal changes in recovery status among individuals in remission from DSM‐IV alcohol dependence, including rates and correlates of relapse, over a 3‐year period.Methods:  This analysis is based on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of U.S. adults aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM‐IV criteria for full remission from alcohol dependence. Of these, 1,772 were reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery status at Wave 2 was examined as a function of type of remission at Wave 1, with a focus on rates of relapse, alternately defined as recurrence of any alcohol use disorder (AUD) symptoms and recurrence of DSM‐IV alcohol dependence. Logistic regression models were used to estimate the odds of relapse among asymptomatic risk drinkers and low‐risk drinkers relative to abstainers, adjusted for a wide range of potential confounders.Results:  By Wave 2, 51.0% of the Wave 1 asymptomatic risk drinkers had experienced the recurrence of AUD symptoms, compared with 27.2% of low‐risk drinkers and 7.3% of abstainers. Across all ages combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great for low‐risk drinkers. The proportions of individuals who had experienced the recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and 3.0 for low‐risk drinkers. Age significantly modified the association between type of remission and relapse. Differences by type of remission were not significant for younger alcoholics, who had the highest rates of relapse.Conclusions:  Abstinence represents the most stable form of remission for most recovering alcoholics. Study findings highlight the need for better approaches to maintaining recovery among young adults in remission from alcohol dependence, who are at particularly high risk of relapse.
The Relationship Between Alcohol Problems and Dependence, Conduct Problems and Diagnosis, and Number of Sex Partners in a Sample of Young Adults
Authors: Cavazos‐Rehg Patricia A. , Spitznagel Edward L. , Bucholz Kathleen K. , Norberg Karen , Reich Wendy , Nurnberger John , Hesselbrock Victor , Kramer John , Kuperman Sam , Bierut Laura Jean 
Published: November 2007

Background:  Heavy drinking is associated with an increased number of sexual partners. This study examined the extent to which alcohol dependence and conduct disorder are associated with the number of sexual partners and membership in a risk group of having a high number of sexual partners (10 or more).Methods:  Data were obtained by personal interview from 601 relatives (aged 18 to 25 years) of alcohol‐dependent probands who participated in the Collaborative Study on the Genetics of Alcoholism (COGA) project. Analyses examined the independent contribution of problem drinking (defined as having at least one symptom of DSM‐IV alcohol dependence) and alcohol dependence, some conduct problems (defined as having at least one symptom of DSM‐IV conduct disorder), conduct disorder, family status (defined as whether participant lived with both biological parents during childhood), educational attainment, gender, race, age at first intercourse, and age at time of interview to the number of sexual partners and to having 10 or more sexual partners.Results:  After controlling for other variables, alcohol dependence, problem drinking, race, age at first intercourse, and age at time of interview were significantly associated with number of sexual partners. The risk for having 10 or more sexual partners rose substantially for those who were alcohol dependent (OR = 2.5, 1.3–4.5, p = 0.004) and those with conduct disorder (OR = 1.8, 1.0–3.3, p = 0.041) after controlling for other variables. There is also a trend toward problem drinking and some conduct problems being associated with the risk of having 10 or more sexual partners though this did not reach statistical significance.Conclusions:  These analyses demonstrate that alcohol‐dependent individuals and those with conduct disorder are at risk for increased number of sexual partners (10 or more). Sexually transmitted disease prevention efforts should target individuals with these two conditions to help decrease high risk sexual behaviors.
Ethanol Alters Production and Secretion of Estrogen‐Regulated Growth Factors That Control Prolactin‐Secreting Tumors in the Pituitary
Authors: Sarkar Dipak K. , Boyadjieva Nadka I. 
Published: November 2007

Background:  Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol’s mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol’s lactotropic cell‐proliferating action, like estradiol’s, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF‐β1), TGF‐β3 and basic fibroblast growth factor (bFGF).Methods:  Using ovariectomized Fischer‐344 female rats, we determined ethanol’s and estradiol’s actions on lactotropic cell proliferation and growth‐regulatory peptide production and release in the pituitary gland during tumorigenesis.Results:  Ethanol increased basal and estradiol‐enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth‐inhibitory TGF‐β1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth‐stimulatory TGF‐β3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF‐β1 release and increased TGF‐β3 and bFGF release at 24 hours. Ethanol’s effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified.Conclusions:  These results confirm estradiol’s modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth‐regulatory peptides controlling lactotropic cell proliferation.
Absence of Significant Interactive Effects of High‐Dosed‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineBSite of NMDA Glutamate Receptors
Authors: Trevisan Louis , Petrakis Ismene L. , Pittman Brian , Gueorguieva Ralitza , D’Souza D. Cyril , Perry Edward , Limoncelli Diana , Krystal John H. 
Published: November 2007

Background: Ethanol reducesN‐methyl‐d‐aspartate (NMDA) glutamate receptor function via multiple cellular targets. It is not yet clear whether direct ethanol antagonism of the glycineBco‐agonist site of NMDA receptors is relevant to this effect. The purpose of this study was to evaluate whether ethanol effects at the glycineBco‐agonist site was clinically relevant by evaluating some aspects of the psychopharmacologic interactions between the glycineBpartial agonist,d‐cycloserine (DCS), and ethanol in healthy human subjects.Methods: All subjects completed 4 test days under double‐blind conditions in which DCS or placebo was administered orally prior to ethanol or an ethanol‐tainted placebo drink. Two groups of healthy subjects were studied. A first group of subjects (n = 25) were pretreated orally with DCS 500 mg or placebo 4 hours prior to ethanol (0.8 g/kg, p.o. or placebo) administration. A second group of subjects (n = 20) were pretreated with DCS 1000 mg or placebo prior to ethanol administration. Outcomes included subjective and cognitive responses to the experimental interventions.Results: Predictable ethanol responses were observed in both groups of subjects, although the response to ethanol and the breath alcohol levels, but not plasma alcohol levels, were slightly but significantly lower in the group that received the higher DCS dose. DCS produced mild sedative effects that were greater for the lower than the higher dose. It also produced a mild impairment of verbal fluency without impairing attention. No statistically significant interactions between ethanol and DCS emerged in analyses. However, the combination of ethanol and DCS produced significantly greater impairment than both ethanol or DCS administered alone on a test of verbal fluency and aspects of memory function.Implications: DCS and ethanol both produced sedative and cognitive effects, consistent with their ability to reduce NMDA receptor function. However, the absence of interactive effects observed in this study raises questions about the clinical significance of the glycineBsite as a target for ethanol in the brain at levels of ethanol intoxication associated with social drinking. However, it should be noted that this conclusion is limited to the dependent measures evaluated and the doses of ethanol and DCS studied.
Chronic Alcohol Feeding Impairs mTOR(Ser2448) Phosphorylation in Rat Hearts
Authors: Vary Thomas C. , Deiter Gina , Lantry Rachel 
Published: November 2007

Background:  Chronic alcohol administration impairs protein synthesis ultimately causing a loss of proteins in cardiac muscle. Inhibition of protein synthesis resides in the process of mRNA translation. The present set of experiments were designed to examine the potential regulatory effect of chronic alcohol consumption on mammalian target of rapamycin (mTOR), a serine/threonine kinase important in controlling signaling cascades in the mRNA translation initiation pathway in rat hearts.Methods:  Rats were fed a diet containing ethanol for 20 to 26 weeks. Pair‐fed rats served as controls. Rates of protein synthesis were measured following intravenous infusion of [3H]‐l‐phenylalanine (150 mM, 30 μCi/ml; 1 ml/100 g body weight). The phosphorylation state of mTOR, eukaryotic initiation factor 4G (eIF4G), protein kinase B (PKB) and S6K1 in heart were measured using immunoblot techniques with phospho‐specific antibodies.Results:  Protein synthesis was reduced by 35% in animals consuming a diet containing ethanol. The fall in protein synthesis was accompanied by diminished S6K1(Thr389) and eIF4G (Ser1108) phosphorylation, both downstream effectors of mTOR signaling. These changes in phosphorylation of S6K1 and eIF4G were not associated with differences in the distribution of mTOR between TORC1 and TORC2. Instead, phosphorylation of mTOR on Ser2448 but not on Ser2481 was significantly reduced following feeding rats an ethanol containing diet. Decreased phosphorylation of mTOR(Ser2448) was not associated with a corresponding lessening of tumor suppressor complex 2 phosphorylation or expression of regulated in development and DNA damage 1, both upstream regulators of mTOR. Likewise, phosphorylation of PKB on either Ser473 or Thr308 was unaffected by long‐term alcohol consumption.Conclusions:  Chronic ethanol consumption does not alter the distribution of mTOR between TORC1 and TORC2, but instead diminishes mTOR phosphorylation on Ser2448 independent of changes in tumor suppressor complex 2 and PKB phosphorylation. Furthermore, the data suggest that protein synthesis in rats fed a diet containing ethanol is limited by mTOR‐dependent reduction in phosphorylation of S6K1(Thr389) and eIF4G(Ser1108) secondary to reduced phosphorylation of mTOR(Ser2448).
A Complex Relationship Between Co‐occurring Social Anxiety and Alcohol Use Disorders: What Effect Does Treating Social Anxiety Have on Drinking?
Authors: Thomas Suzanne E. , Randall Patrick K. , Book Sarah W. , Randall Carrie L. 
Published: November 2007

Background:  Individuals with social anxiety disorder and co‐occurring alcohol problems report using alcohol to cope with anxiety symptoms. Interventions that reduce both social anxiety and drinking are needed. Paroxetine, an FDA‐approved medication to treat social anxiety disorder, reduces anxiety in individuals with co‐occurring alcohol problems.Objectives:  To examine whether effective treatment of social anxiety with paroxetine reduces drinking in dual‐diagnosed individuals who endorse using alcohol to cope.Methods:  A 16‐week, double‐blind, randomized controlled trial of paroxetine was conducted. Participants (placebo n = 22; paroxetine n = 20) met DSM‐IV diagnostic criteria for social anxiety disorder and alcohol abuse or dependence. Participants were seeking treatment for social anxiety, not for the alcohol problem. Alcohol use outcomes were measured with conventional quantity/frequency measures and novel measures of drinking to cope.Results:  Paroxetine improved social anxiety more than placebo. Paroxetine reduced self‐reported reliance on alcohol for self‐medication purposes, but was not different than placebo in changing quantity and frequency drinking or the proportion of drinking days that were identified as coping‐related. Exploratory analyses revealed that for the placebo group, drinking during the trial was correlated with social anxiety severity, whereas for the paroxetine‐treated group, drinking was uncoupled from social anxiety severity.Conclusions:  Successfully treating social anxiety symptoms with paroxetine does not reduce drinking in dual‐diagnosed individuals who are not seeking treatment for alcohol problems. Paroxetine does, however, reduce reliance on alcohol to engage in social situations, and may change the reasons why one drinks (such that drinking occurs for other reasons besides coping with anxiety). These results have implications for staging of social anxiety and alcohol treatment in individuals with the co‐occurring disorders presenting to a mental health or primary care provider.
Person and Environment Predictors of Blood Alcohol Concentrations: A Multi‐Level Study of College Parties
Authors: Clapp John D. , Min Jong Won , Shillington Audrey M. , Reed Mark B. , Ketchie Croff Julie 
Published: November 2007

Aims:  This study builds upon previous research by assessing the relationship of breath blood alcohol concentrations (BrAC) to environmental and individual characteristics.Design:  We conducted a multi‐level study of college parties. Our design included observational measures of party environments, a brief self‐administered questionnaire, and the collection of breath samples from partygoers.Setting:  Data were collected in private residences of students living in a neighborhood adjacent to a large public university located in the Southwestern United States.Participants:  A total of 1,304 individuals attending 66 parties participated in the study.Measures:  Observational measures of party characteristics were made by 2 trained research assistants at each party. Four to 5 trained interviewers administered a brief field survey to partygoers at each party. In addition, the trained interviewers collected breath samples using handheld breathalyzer devices.Findings:  Hierarchical linear modeling analyses revealed significant variation at the party and individual levels. At the individual level, motivations to socialize were significantly associated with lower BrAC, while drinking games and providing the sample after 11:00 pm were associated with higher BrACs. At the party level, large parties were significantly associated with lower BrACs while reports of many intoxicated partygoers were associated with higher BrACs. Finally, we identified a significant gender by theme party interaction, indicating women had higher BrACs at theme parties relative to nontheme parties; however, BrACs for men were similar regardless of the type of party attended.Conclusions:  Alcohol consumption among young adults in natural settings is a function of both person and environmental factors.
Evaluation of the Effect of Ethanol’s Toxic Metabolite Acetaldehyde on the Gastrointestinal Oligopeptide Transporter, PEPT1: In Vitro and in Vivo Studies
Authors: Fisher Scott J. , Lee Insong J. , Swaan Peter W. , Eddington Natalie D. 
Published: November 2007

Background: The effects of alcohol consumption and its subsequent metabolism on drug transport, absorption and pharmacokinetics are poorly understood. This study examines the effects of the ethanol metabolite, acetaldehyde, on the clinically relevant drug transporter, PEPT1. The metabolism of ethanol and the following acetaldehyde formation is thought to modulate the uptake capacity of PEPT1 within the gastrointestinal tract for a variety of clinically important peptidomimetic drug compounds.Methods: Glycylsarcosine ([3H]‐GlySar), a nonhydrolysable PEPT1 specific substrate was used in our studies. In vitro uptake studies were performed in the Caco‐2 and Chinese hamster ovary (CHO)‐hPEPT1 cell models, measuring cellular uptake of labeled compound against increasing levels of unlabeled compound in the presence of acetaldehyde. In vivo absorption of [3H]‐GlySar was measured in male Sprague–Dawley rats that were treated with oral dose of ethanol/disulfiram (5 g/kg / 100 mg/kg) for 6 days. These results were compared to control rats treated with saline, ethanol alone or disulfiram alone.Results: In vitro uptake of [3H]‐GlySar in CHO‐hPEPT1 cells treated with 1 mM acetaldehyde was significantly decreased (p < 0.05) as compared to untreated controls. The uptake of [3H]‐GlySar in Caco‐2 cell monolayers treated with 1 mM acetaldehyde was also significantly decreased as compared to the untreated control cells. In vivo absorption of [3H]‐GlySar in ethanol treated rats, as measured by AUC0–12 hourswere decreased by approximately 50% versus the control rat group.Conclusion: The effects of acetaldehyde due to consumption of ethanol on the uptake and bioavailability of therapeutic drug compounds transported by the PEPT1 oligopeptide transporter have not been documented. In the present studies, we demonstrate that acetaldehyde significantly modulates PEPT1 function and, thereby, affects drug bioavailability. To our best knowledge, this is the first report on the effects of an ethanol metabolite on substrate absorption in the gastrointestinal tract, rather than interactions in the liver, which is an under‐represented area of research in alcohol pathophysiology.
How Would Terminally Ill Patients Have Others Make Decisions for Them in the Event of Decisional Incapacity? A Longitudinal Study
Authors: Sulmasy Daniel P. , Hughes Mark T. , Thompson Richard E. , Astrow Alan B. , Terry Peter B. , Kub Joan , Nolan Marie T. 
Published: November 2007

OBJECTIVES:To determine the role terminally ill patients would opt to have their loved ones and physicians play in healthcare decisions should they lose decision‐making capacity and how this changes over time.DESIGN:Serial interviews.SETTING:The study institutions were The Johns Hopkins Medical Institutions in Baltimore, Maryland, and St. Vincent's Hospital, in New York.PARTICIPANTS:One hundred forty‐seven patients with cancer, amyotrophic lateral sclerosis, or heart failure, at baseline and 3 and 6 months.RESULTS:Patients' baseline decision control preferences varied widely, but most opted for shared decision‐making, leaning slightly toward independence from their loved ones. This did not change significantly at 3 or 6 months. Fifty‐seven percent opted for the same degree of decision control at 3 months as at baseline. In a generalized estimating equation model adjusted for time, more‐independent decision‐making was associated with college education (P=.046) and being female (P=.01), whereas more‐reliant decision‐making was associated with age (P<.001). Patients leaned toward more reliance upon physicians to make best‐interest determinations at diagnosis but opted for physicians to decide based upon their own independent wishes (substituted judgment) over time, especially if college educated.CONCLUSION:Terminally ill patients vary in how much they wish their own preferences to control decisions made on their behalf, but most would opt for shared decision‐making with loved ones and physicians. Control preferences are stable over time with respect to loved ones, but as they live longer with their illnesses, patients prefer somewhat less reliance upon physicians.