Browsing by Author "O'Connor, Sean"

Now showing 1 - 10 of 11
  • Thumbnail Image
    Item
    Adolescent women induce lower blood alcohol levels than men in a laboratory alcohol self-administration experiment
    (Wiley, 2016-08) Jünger, Elisabeth; Gan, Gabriela; Mick, Inge; Seipt, Christian; Markovic, Alexandra; Sommer, Christian; Plawecki, Martin H.; O'Connor, Sean; Smolka, Michael N.; Zimmermann, Ulrich S.; Psychiatry, School of Medicine
    Background Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive Family History of alcoholism (FH), are often masked by environmental factors such as peer pressure. Methods We investigated how sex and FH modulate alcohol use in a sample of 18-19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults (D-LAYA). Adolescents reported their real-life drinking in a TimeLine Follow-Back (TLFB) interview. They subsequently completed a training and an experimental session of free-access intravenous Alcohol Self-Administration (i.v. ASA) using the computer-assisted alcohol infusion system in order to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at eight time points. Results Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial Blood Alcohol Concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the two sessions. Conclusions We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm.
  • Thumbnail Image
    Item
    Alcohol intoxication progressively impairs drivers' capacity to detect important environmental stimuli
    (Elsevier, 2018) Plawecki, Martin Henry; Koskie, Sarah; Kosobud, Ann; Justiss, Michael D.; O'Connor, Sean; Psychiatry, School of Medicine
    Rationale Alcohol intoxication impairs driving skills, leading to an increased frequency of accidents and crash fatalities. Inebriation may specifically impair environmental vigilance, reducing the driver's capacity for attention to stimuli that are relevant to successful navigation. Objectives We examined the separate and interactive effects of breath alcohol concentration (BrAC) and simulated driving scenario on the capacity to correctly identify visual stimuli embedded in the environment. Methods Ten healthy young adult drivers (6 males; 4 females) each performed 4 driving scenarios at each of 3 steady breath alcohol concentration levels (0, 60 and 100 mg/dl). Scenarios were based on speed or distance keeping while navigating a rural 2-lane road in daytime or nighttime conditions. Drivers pressed a button on the steering wheel corresponding to the direction of an arrow (up or down) which appeared briefly on road signs embedded in the environment, either overhead or on the roadside. Results Increasing level of BrAC and subjective scenario difficulty manifested significant, separate, but not interactive influences in association with the number of arrows correctly identified. Significant impairments could be detected at a level of BrAC below the current American limit for legal operation of a motor vehicle. Conclusions Environmental vigilance is subject to impairment by either/both alcohol intoxication and driving conditions.
  • Thumbnail Image
    Item
    Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration under Similar Systemic Exposures
    (Wiley, 2019) Plawecki, Martin H.; Durrani, A. M.; Boes, Julian; Wetherill, Leah; Kosobud, Ann; O'Connor, Sean; Ramchandani, V. A.; Psychiatry, School of Medicine
    Objective To test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by intravenous administration. Background Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous alcohol administration techniques, and any differences attributable to the route employed should be understood. Methods We conducted a 2‐session, within‐subject study in 44 young adult, healthy, non‐dependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an intravenous alcohol infusion rate profile, pre‐computed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. Results No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. Conclusion The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar.
  • Thumbnail Image
    Item
    Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics
    (Elsevier, 2016-03) Yoder, Karmen K.; Albrecht, Daniel S.; Dzemidzic, Mario; Normandin, Marc D.; Federici, Lauren M.; Graves, Tammy; Herring, Christine M.; Hile, Karen L.; Walters, James W.; Liang, Tiebing; Plawecki, Martin H.; O'Connor, Sean; Kareken, David A.; Department of Radiology and Imaging Sciences, IU School of Medicine
    Background Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). Methods Twenty-four SD and twenty-one NTS received two [11C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then “clamped.” The alcohol clamp was started 5 min after scan start, with a linear increase in BrAC over 15 min to the target of 80 mg%, the legal threshold for intoxication. Target BrAC was maintained for 30 min. Voxel-wise binding potential (BPND) was estimated with MRTM2. Results IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. Conclusions Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD.
  • No Thumbnail Available
    Item
  • Thumbnail Image
    Item
    Fat-free mass accounts for most of the variance in alcohol elimination rate in women
    (Wiley, 2023) Seyedsadjadi, Neda; Ramchandani, Vijay A.; Plawecki, Martin H.; Kosobud, Ann E. K.; O'Connor, Sean; Rowitz, Blair; Pepino, Marta Yanina; Psychiatry, School of Medicine
    Background: Understanding how blood alcohol concentrations (BAC) achieved after drinking are determined is critical to predicting alcohol exposure to the brain and other organs and alcohol's effects. However, predicting end-organ exposures is challenging, as there is wide variation in BAC achieved after drinking a specified volume of alcohol. This variation is partly due to differences in body composition and alcohol elimination rates (AER), but there are limited data on how obesity affects AER. Here, we assess associations between obesity, fat-free mass (FFM), and AER in women and examine whether bariatric surgeries, which are linked to an increased risk of alcohol misuse, affect these associations. Methods: We analyzed data from three studies that used similar intravenous alcohol clamping procedures to estimate AER in 143 women (21 to 64 years old) with a wide range of body mass index (BMI; 18.5 to 48.4 kg/m2 ). Body composition was measured in a subgroup using dual-energy X-ray absorptiometry (n = 42) or Bioimpedance (n = 60), and 19 of the women underwent bariatric surgery 2.1 ± 0.3 years before participation. We analyzed data using multiple linear regression analyses. Results: Obesity and older age were associated with a faster AER (BMI: rs = 0.70 and age: rs = 0.61, both p < 0.001). Compared to women with normal weight, AER was 52% faster (95% Confidence Interval: 42% to 61%) in women with obesity. However, BMI lost predictive value when adding fat-free mass (FFM) to the regression model. Age, FFM, and its interaction explained 72% of individual variance in AER (F (4, 97) = 64.3, p < 0.001). AER was faster in women with higher FFM, particularly women in the top tertile of age. After controlling for FFM and age, bariatric surgery was not associated with differences in AER (p = 0.74). Conclusions: Obesity is associated with a faster AER, but this association is mediated by an obesity-related increase in FFM, particularly in older women. Previous findings of a reduced alcohol clearance following bariatric surgery compared with prior to surgery are likely explained by a reduction in FFM post-surgery.
  • Thumbnail Image
    Item
    Gender Specific Effects of Mood on Alcohol Seeking Behaviors: Preliminary Findings using Intravenous Alcohol Self-Administration
    (Wiley, 2016-02) Cyders, Melissa A.; VanderVeen, J. Davis; Plawecki, Martin; Millward, James B.; Hays, James; Kareken, David A.; O'Connor, Sean; Department of Psychology, School of Science
    Background Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well-controlled laboratory experiments to examine how negative mood affects alcohol-seeking behaviors. Methods A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21 to 32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian; Alcohol Use Disorders Identification Test [AUDIT] = 10.1, SD = 3.4) completed 2 counterbalanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age = 25.00, SD = 2.77) participated in an alcohol “liking” experiment (i.e., free access [FA] drinking) and 20 individuals (10 women; mean age = 24.77, SD = 3.73) participated in an alcohol “wanting” experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT, t(32) = −0.38, p = 0.71. Results Priming with negative mood induction caused a significant decrease in self-reported mood (mean change = −1.85, t(32) = −6.81, p < 0.001), as intended. In FA, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F = 9.41, p = 0.01), with a trend toward a greater effect in men than in women (F = 2.67, p = 0.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F = 5.28, p = 0.04), with a significantly stronger effect in men (F = 5.35, p = 0.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. Conclusions These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption.
  • Thumbnail Image
    Item
    Sensation Seeking, Impulsivity, and Aggression Moderate Sex Effects on Adolescent Laboratory Binging
    (APA, 2021-03) Obst, Elisabeth; Bernhardt, Nadine; Gan, Gabriela; Plawecki, Martin H.; O'Connor, Sean; Smolka, Michael N.; Zimmermann, Ulrich S.; Psychiatry, School of Medicine
    Sex, comprising biological and gender-related distinctions, is a known risk factor for alcohol use disorders. Moreover, sensation seeking, impulsivity, and aggression have been found to predict binge drinking and to reflect behavioral disinhibition. We tested effects of these disinhibited traits on binging during intravenous alcohol self-administration (ivASA), a method that eliminates sex differences in the pharmacokinetics of alcohol. Eighty-five German social drinkers (49 men) completed 3 questionnaires assessing sensation seeking, impulsivity, and aggression, as well as an ivASA session at ages 18–19. Sixty-five of them were retested at ages 21–22. Participants reported real-life drinking problems and the number of binge days in the 45 days preceding lab testing. Analyses employed continuous data and median splits to examine associations between disinhibited traits and the portion of women and men in the sample who achieved a breath alcohol concentration of 80 mg% during ivASA (“binge fraction”). At ages 18–19, and only if scoring low on sensation seeking, impulsivity, or aggression, women had significantly lower binge fractions during ivASA than men. Further, low compared to high impulsivity or aggression predicted lower binge fractions in women but not in men. Neither first- nor second-wave disinhibited traits significantly predicted binge fractions at ages 21–22. We perceive that personality traits reflecting behavioral disinhibition might be a strong indicator of drinking problems, specifically among young women. Targeted brief interventions might therefore be used in educational or clinical settings to inform such women about their increased risk and the potential health and behavioral problems associated with binge drinking.
  • Thumbnail Image
    Item
    Sex Differences in Motivation to Self‐Administer Alcohol After 2 Weeks of Abstinence in Young‐Adult Heavy Drinkers
    (Wiley, 2018) Plawecki, Martin Henry; White, Kurt; Kosobud, Ann E. K.; Grahame, Nicholas; Zimmermann, Ulrich S.; Crabb, David; O'Connor, Sean; Psychiatry, School of Medicine
    Background Studies in animal models document that forced abstinence from usual consumption of alcohol changes subsequent seeking and consumption, with increases or decreases depending on the species, duration of abstinence, number of deprivations, and sex. Human laboratory‐based alcohol deprivation studies are rare. Methods We conducted a 2‐session, within‐participant, randomized‐order comparison of intravenous, progressive ratio, alcohol self‐administration during 2.5 hours of progressive work for alcohol and/or vehicle; once while the participants pursued their usual drinking habits and once after 2 weeks of closely monitored, voluntary outpatient abstinence from alcohol. The schedule of work for rewards and the incremental increases in breath alcohol concentration following completion of an alcohol work‐set were identical across participants. Fifty young‐adult (27 men), heavy‐drinking participants completed both sessions. Our primary hypothesis was that motivation to work for alcohol after 2 weeks of abstinence would be greater in participants with a weekly binge pattern of drinking, compared to those who regularly drink heavily, and we intended to explore associations with biological family history of alcoholism and sex. Results We detected no change in work for alcohol associated with recent drinking history. However, females, on average, increased their work for alcohol upon resumption after 2 weeks of abstinence (mean ± SEM = +16.3 ± 9.6%), while males decreased that work (−24.8 ± 13.8%). The sex difference was substantial and significant (p < 0.03), with a medium effect size (Cohen's d = 0.63). Conclusions We believe a more comprehensive study of mechanisms underlying the sex differences in the human postabstinence response is warranted.
  • Thumbnail Image
    Item
    Stress Vulnerability And Alcohol Use And Consequences: From Human Laboratory Studies To Clinical Outcomes
    (Elsevier, 2018) Ramchandani, Vijay A.; Stangl, Bethany L.; Blaine, Sara K.; Plawecki, Martin H.; Schwandt, Melanie L.; Kwako, Laura E.; Sinha, Rajita; Cyders, Melissa A.; O'Connor, Sean; Zakhari, Samir; Psychiatry, School of Medicine
    It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress – past, acute and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms – mood induction and abstinence – on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure.