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Cited by 132Substance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on BehaviorAlcohol Consumption and Health Effects

A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder

Open access
King, Andrea C., Hasin, Deborah, O’Connor, Sean J., McNamara, Patrick J., Cao, Dingcai·2016·Biological Psychiatry
DOI 10.1016/j.biopsych.2015.05.007PMC PMC4644521
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Abstract

Background The main neurobiological theories of the development of addiction, including tolerance, sensitization, incentive-sensitization, and allostasis have not been tested in longitudinal human alcohol response research. To address this issue, we conducted the first controlled prospective investigation of subjective and neuroendocrine responses to alcohol measured over a five year interval in at-risk young adult heavy drinkers and light drinker controls. Methods Participants were 156 individuals, 86 heavy drinkers (HD) and 70 light drinkers (LD), undergoing an initial oral alcohol challenge testing (0.8 g/kg alcohol vs. placebo) and an identical re-examination testing 5–6 years later. Alcohol use disorder (AUD) symptoms and drinking behaviors were assessed in the interim follow-up period. Results At reexamination, HD continued to exhibit higher sensitivity on alcohol’s stimulating and rewarding effects with lower sensitivity to sedative effects and cortisol reactivity, relative to LD. In HD with high AUD symptom trajectories over follow-up, heightened alcohol stimulation and reward persisted at reexamination. HD with low AUD symptoms showed reduced alcohol stimulation over time and lower reward throughout compared with the HD with high and intermediate AUD symptoms. Conclusions Results support the early stage phase of the allostasis model, with persistently heightened reward sensitivity and stimulation in heavy drinkers exhibiting AUD progression in early mid-adulthood. While there are multiple pathways to development of a disorder as complex as AUD, maintenance of alcohol stimulatory and rewarding effects may play an important role in the continuation and progression of alcohol addiction.

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Written from the paper’s full text.

TL;DR

This prospective 5–6 year re-examination of heavy and light drinkers found that heavy drinkers continued to show heightened alcohol stimulation and reward and lower sedation and cortisol responses relative to light drinkers. Among heavy drinkers, those with high or intermediate AUD symptom trajectories maintained heightened reward, while those with low AUD symptoms showed reduced alcohol stimulation over time.

Key findings

  • At re-examination, heavy drinkers (HD) continued to exhibit higher sensitivity to alcohol’s stimulating and rewarding effects and lower sensitivity to sedative effects and cortisol reactivity than light drinkers (LD).
  • In HD with high AUD symptom trajectories, heightened alcohol stimulation and reward persisted at re-examination; HD with low AUD symptoms showed reduced alcohol stimulation over time and lower reward throughout compared with high and intermediate AUD symptom groups.
  • Peak BrAC at 60 minutes was slightly higher at initial testing in HD vs. LD (94 vs. 85 mg/dl, p<.001), but at re-examination there were no differences (89 vs. 85 mg/dl, p=.126); all analyses controlled for peak BrAC.
  • Within-subject associations between initial and re-examination responses were positive and significant: stimulation r=.30, liking r=.26, wanting r=.30, sedation r=.42, and cortisol r=.18 (p<.05).

Methods

  • Design: within-subject, double-blind, randomized-order study of oral alcohol challenge (0.8 g/kg alcohol vs. placebo) in 190 young adult non-alcohol-dependent drinkers at enrollment; 156 returned for re-examination (86 HD, 70 LD) an average of 63 months (±1.5 SD) later.
  • Procedures: two 4½-hour individual sessions per phase, separated by at least 24 hours, with measures before and after blinded beverage; subjective stimulation/sedation via BAES, liking/wanting via DEQ, and salivary cortisol; AUD symptoms and drinking behaviors assessed during interim annual follow-ups.
  • Analysis: Generalized Estimating Equations tested group (HD, LD), phase, and interactions; Pearson correlations examined within-subject associations; trajectory analysis identified low, intermediate, and high AUD symptom subgroups among HD.

Limitations

  • Stated: the re-examination interval may not have been sufficient to observe the full extent of neuroadaptive responses to alcohol; beverages were consumed over a short interval to capture direct effects and minimize variability, which may not translate to typical drinking situations.
  • Stated: trajectory analyses resulted in unequal subgroup sample sizes, and participants under age 21 were not enrolled due to legal restrictions on alcohol administration in the U.S., precluding study of earlier developmental periods.
  • Evident from the text: the sample excluded individuals with current or past major medical or Axis I psychiatric disorders including alcohol and substance dependence, and the authors note that allostasis may occur only in the most extreme alcoholics with significant withdrawal not selected due to ethical constraints; replication is stated as a necessary next step.

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Crossref · 10.1016/j.biopsych.2015.05.007

Cites

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Statistics

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Claims the paper makes

0 of 69 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    These correlations were not significant in the low AUD subgroup.

    “these correlations were not significant in the low AUD subgroup (Supplemental Results).”
    Quote in the paperNot a substantial claim
  • Findingown data

    For alcohol reward, there were main effects of AUD subgroup: relative to the low AUD subgroup, the high and intermediate AUD subgroups had persistently higher alcohol liking and wanting over time than the low AUD subgroup.

    “For alcohol reward, there were main effects of AUD subgroup: relative to the low AUD subgroup, the high and intermediate AUD subgroups had persistently higher alcohol liking and wanting over time than the low AUD subgroup.”
    Quote in the paperSubstantial claim
  • Findingown data

    The HD comprised three AUD subgroups over time, derived by trajectory analysis which differentiated those with low, intermediate, and high symptoms.

    “In contrast, the HD comprised three AUD subgroups over time, derived by trajectory analysis which differentiated those with low, intermediate, and high symptoms (see Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    At both phases, relative to LD, HD exhibited higher sensitivity to alcohol stimulating and rewarding effects.

    “In brief, at both phases, relative to LD, HD exhibited higher sensitivity to alcohol stimulating and rewarding effects (Fig 2A–2C).”
    Quote in the paperSubstantial claim
  • Findingown data

    The relationships of stimulation, liking and wanting were positive for the high and intermediate AUD subgroups.

    “The relationships of stimulation, liking and wanting were positive for the high and intermediate AUD subgroups, suggesting that stimulation is pleasurable; these correlations were not significant in the low AUD subgroup (Supplemental Results).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 29

  • May combine two claims.

    Findingcitation

    The LD largely continued with low-risk drinking; while they consumed alcohol more frequently over time, binge drinking and alcohol problems were rare, and they formed one low-risk trajectory group.

    “In brief, the LD largely continued with low-risk drinking. While they consumed alcohol more frequently over time, binge drinking and alcohol problems were rare, and they formed one low-risk trajectory group(34).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] King, 2014, Alcohol challenge responses predict future alcohol use disorder symptoms: A 6-year prospective study, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    BrAC peak levels at 60 minutes were slightly higher at initial testing in the HD vs. LD (94 vs. 85 mg/dl, respectively, p<.001) but at re-examination there were no differences [89 vs. 85 mg/dl, p=.126].

    “BrAC peak levels at 60 minutes were slightly higher at initial testing in the HD vs. LD (94 vs. 85 mg/dl, respectively, p<.001) but at re-examination there were no differences [89 vs. 85 mg/dl, p=.126].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For the HD subgroups, there was a subgroup x phase interaction for stimulation such that the high AUD subgroup persisted with heightened stimulation at re-examination and the intermediate group persisted at intermediate levels, but the low AUD subgroup showed a reduction in stimulation over time.

    “For the HD subgroups, there was a subgroup x phase interaction for stimulation such that the high AUD subgroup persisted with heightened stimulation at re-examination and the intermediate group persisted at intermediate levels, but the low AUD subgroup showed a reduction in stimulation over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Within-subject associations of each alcohol response between initial and re-examination phases were positive and significant [stimulation (r=.30, p<.001), liking (r=.26, p<.001), wanting (r=.30, p<.001), sedation (r=.42, p<.0001), and cortisol (r=.18, p<.05)].

    “Within-subject associations of each alcohol response between initial and re-examination phases were positive and significant [stimulation (r=.30, p<.001), liking (r=.26, p<.001), wanting (r= .30, p<.001), sedation (r=.42, p<.0001), and cortisol (r= .18, p<.05)].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HD had lower sensitivity to sedation and cortisol response versus LD.

    “HD also had lower sensitivity to sedation (Fig 3A) and cortisol response versus LD (Fig 3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The majority of persons in this subgroup either maintained heightened stimulation or increased further at re-examination, with only 2 of 9 high AUD individuals showing a lessening of response.

    “the majority of persons in this subgroup either maintaining heightened stimulation or increasing further at re-examination, with only 2 of 9 high AUD individuals showing a lessening of response.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The AUD subgroups did not differ on alcohol sedation or cortisol response.

    “The AUD subgroups did not differ on alcohol sedation or cortisol response (Fig 3A, 3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At the declining limb, stimulating and rewarding responses were lower in magnitude than at the earlier time points but heightened responses remained in HD, particularly for wanting in the high AUD subgroup.

    “At the declining limb, stimulating and rewarding responses were lower in magnitude than at the earlier time points but heightened responses remained in HD, particularly for wanting in the high AUD subgroup.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Light drinkers largely continued low-risk drinking and rare AUD symptoms over time with an overall protective alcohol response 'footprint': persistently low sensitivity to alcohol stimulation and reward and high sensitivity to alcohol sedative and stress hormone effects.

    “Light drinkers largely continued low-risk drinking and rare AUD symptoms over time with an overall protective alcohol response “footprint”: persistently low sensitivity to alcohol stimulation and reward and high sensitivity to alcohol sedative and stress hormone effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The results did not support sensitization theory, as heavy drinkers with progressive AUD maintained but did not further increase their already heightened sensitivity to stimulation.

    “Finally, the results did not support sensitization theory, as heavy drinkers with progressive AUD subjects maintained but did not further increase their already heightened sensitivity to stimulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Alcohol response differences between heavy drinkers and light drinker controls observed at initial testing remained 5-6 years later, with greater alcohol stimulating and rewarding effects and lower sedation and cortisol excretion in heavy drinkers.

    “Alcohol response differences between these groups observed at initial testing remained 5–6 years later, with greater alcohol stimulating and rewarding effects and lower sedation and cortisol excretion in heavy drinkers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Human studies in this area have been limited to retrospective patient reports, post mortem brain tissue methods, or cross-sectional laboratory paradigms, none of which directly measure alcohol responses in the same individuals over time.

    “Human studies in this area have been limited to retrospective patient reports(23), post mortem brain tissue methods(24), or cross-sectional laboratory paradigms(2, 3, 25–29), none of which directly measure alcohol responses in the same individuals over time.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [23] Edwards, 1976, Alcohol dependence: Provisional description of a clinical syndrome, Br Med J source

      Not checked in the free run.

    • cites [24] Hutchison, 2008, The incentive salience of alcohol: Translating the effects of genetic variant in CNR1, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [2] Corbin, 2013, Early subjective response and acquired tolerance as predictors of alcohol use and related problems in a clinical sample, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [3] Morean, 2008, Subjective alcohol effects and drinking behavior: The relative influence of early response and acquired tolerance, Addict Behav source

      Not checked in the free run.

    • cites [25] Ostafin, 2010, Testing the incentive-sensitization theory with at-risk drinkers: Wanting, liking, and alcohol consumption, Psychol Addict Behav source

      Not checked in the free run.

    • cites [26] Hobbs, 2005, Dissociation of wanting and liking for alcohol in humans: A test of the incentive-sensitisation theory, Psychopharmacology (Berl) source

      Not checked in the free run.

    • cites [27] Newlin, 1991, Chronic tolerance and sensitization to alcohol in sons of alcoholics, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [28] Schuckit, 1996, An 8-year follow-up of 450 sons of alcoholic and control subjects, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [29] King, 2011, Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking, Arch Gen Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Tolerance theory implies that attenuation of subjective alcohol responses over time plays a key role in the development of addiction.

    “Tolerance, a diagnostic criteria for AUD from DSM-III (1980) to DSM-5 (2013)(8), implies that attenuation of subjective alcohol responses over time plays a key role in the development of addiction.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [2] Corbin, 2013, Early subjective response and acquired tolerance as predictors of alcohol use and related problems in a clinical sample, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [3] Morean, 2008, Subjective alcohol effects and drinking behavior: The relative influence of early response and acquired tolerance, Addict Behav source

      Not checked in the free run.

    • cites [4] Schuckit, 2008, Clinical implications of tolerance to alcohol in nondependent young drinkers, Am J Drug Alcohol Abuse source

      Not checked in the free run.

    • cites [5] Matson, 2014, Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [6] Tabakoff, 1988, Tolerance and the etiology of alcoholism: Hypothesis and mechanism, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [7] Ramsay, 1997, Biological consequences of drug administration: Implications for acute and chronic tolerance, Psychol Rev source

      Not checked in the free run.

    • cites [8] 2013

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Hedonic reward ('liking') may not sensitize over time.

    “which may not sensitize over time.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Robinson, 1993, The neural basis of drug craving: An incentive-sensitization theory of addiction, Brain Res Brain Res Rev source

      Not checked in the free run.

    • cites [17] Robinson, 2001, Incentive-sensitization and addiction, Addiction source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The present study provided the first comprehensive repeated evaluation of alcohol responses in at-risk drinkers to test these neurobiological theories of AUD progression.

    “The present study provided the first comprehensive repeated evaluation of alcohol responses in at-risk drinkers to test these neurobiological theories of AUD progression.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sensitization theory asserts that greater stimulant effects over time underlie addictive processes.

    “In contrast, the sensitization theory asserts that greater stimulant effects over time underlie addictive processes(9), based on rodent data showing that stimulant-like and locomotor alcohol responses increase after repeated exposures(10, 11).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Wise, 1987, A psychomotor stimulant theory of addiction, Psychol Rev source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Allostatic theory asserts heightened brain reward sensitivity and positive reinforcement characterize the early stages of addiction.

    “Finally, allostatic theory asserts heightened brain reward sensitivity and positive reinforcement characterize the early stages of addiction(18), but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Koob, 2001, Drug addiction, dysregulation of reward, and allostasis, Neuropsychopharmacology source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Allostatic theory asserts reward insensitivity and negative reinforcement underlie the later and more severe stages of addiction.

    “but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Koob, 2001, Drug addiction, dysregulation of reward, and allostasis, Neuropsychopharmacology source

      Not checked in the free run.

    • cites [19] Volkow, 2010, Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit, Bioessays source

      Not checked in the free run.

    • cites [20] Koob, 2008, Addiction and the brain antireward system, Annu Rev Psychol source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Incentive-sensitization theory specifies that repeated use of a drug produces neuroadaptations that sensitize motivational reward to drugs and associated drug stimuli ('wanting') distinct from the neurocircuitry mediating hedonic reward ('liking').

    “The incentive-sensitization theory of addiction(16, 17) also emphasizes sensitization process, but specifies that repeated use of a drug produces neuroadapations that sensitize motivational reward to drugs and associated drug stimuli (i.e.., processes of “wanting”) distinct from the neurocircuitry mediating hedonic reward (liking) which may not sensitize over time.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Robinson, 1993, The neural basis of drug craving: An incentive-sensitization theory of addiction, Brain Res Brain Res Rev source

      Not checked in the free run.

    • cites [17] Robinson, 2001, Incentive-sensitization and addiction, Addiction source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    At the 5-year follow-up, 187 individuals (98.4%) continued to participate.

    “At the 5-year follow-up, 187 individuals (98.4%) continued to participate, and telephone re-screening was conducted to determine eligibility for re-examination.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    From the eligible subject pool, 156 (88% of those eligible, 83% of the original sample) returned to participate in re-examination sessions.

    “From this eligible subject pool, 156 (88% of those eligible, 83% of the original sample) returned to participate in re-examination sessions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    To reduce alcohol expectancy, the Alternative Substance Paradigm was used: participants were informed that their allocated beverage might contain a stimulant, sedative, alcohol, or a placebo, or a combination of these substances.

    “To reduce alcohol expectancy, the Alternative Substance Paradigm(51) was used: participants were informed that their allocated beverage might contain a stimulant, sedative, alcohol, or a placebo, or a combination of these substances.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Conrad, 2012, Alternative substance paradigm: Effectiveness of beverage blinding and effects on acute alcohol responses, Exp Clin Psychopharmacol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The instructions asked for current mood state at each time point and did not reveal that alcohol was ingested.

    “The instructions asked for current mood state at each time point and did not reveal that alcohol was ingested (60).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Rueger, 2009, Expanding the utility of the Biphasic Alcohol Effects Scale (BAES) and initial psychometric support for the Brief-BAES (B-BAES), Alcohol Clin Exp Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Salivary cortisol was assayed by high sensitivity enzyme immunoassay; inter- and intra-assay coefficients of variation at initial testing were 6.88% and 7.12%, respectively, and at re-examination were 6.60% and 7.99%, respectively.

    “Samples were stored at −20°C and later assayed for levels of the stress hormone cortisol by high sensitivity enzyme immunoassay at the University of Chicago CRC Core Laboratory. The inter- and intra-assay coefficients of variation at initial testing were 6.88% and 7.12%, respectively, and at re-examination were 6.60% and 7.99%, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Participants were interviewed to confirm compliance with 3-hour abstinence from food, caffeine, and smoking.

    “Participants were interviewed to confirm compliance with 3-hour abstinence from food, caffeine, and smoking.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The CSDP is a within-subject, double-blind, randomized-order study of responses to alcohol and placebo beverages in 190 young adult non-alcohol dependent drinkers.

    “The CSDP is a within-subject, double-blind, randomized-order study of responses to alcohol and placebo beverages in 190 young adult non-alcohol dependent drinkers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Most participants (95%, 178/187) remained eligible: they were current drinkers with no major medical or psychiatric contraindications.

    “Most participants (95%, 178/187) remained eligible: they were current drinkers with no major medical or psychiatric contraindications.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All analyses controlled for peak BrAC levels at each testing phase.

    “All analyses controlled for peak BrAC levels at each testing phase.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Urine samples were collected prior to one session, chosen randomly, for toxicology in all participants, and prior to each session for women to verify non-pregnancy.

    “Urine samples were collected prior to one session, chosen randomly, for toxicology in all participants, and prior to each session for women to verify non-pregnancy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Analyses were repeated including FH as a covariate with FH coded by 2 dummy variables: FH positive vs. negative, and FH not sure vs. negative.

    “Since FH is as a potential risk factor for development of alcohol problems(64), analyses were repeated including FH as a covariate with FH coded by 2 dummy variables: FH positive vs. negative, and FH not sure vs. negative.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Goodwin, 1973, Alcohol problems in adoptees raised apart from alcoholic biological parents, Arch Gen Psychiatry source

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  • May combine two claims.

    Premisecitation

    Compared with light drinkers, heavy drinkers exhibited higher alcohol sensitivity in subjective stimulation and reward (liking and wanting), as well as lower sensitivity in subjective sedation and salivary cortisol reactivity.

    “Our previously published results showed that compared with light drinkers, heavy drinkers exhibited both higher alcohol sensitivity, in terms of subjective stimulation and reward (liking and wanting)(29), as well as lower sensitivity, in terms of subjective sedation(29), and salivary cortisol reactivity(29, 32).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] King, 2011, Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking, Arch Gen Psychiatry source

      Not checked in the free run.

    • cites [32] King, 2006, Attenuated cortisol response to alcohol in heavy social drinkers, Int J Psychophysiol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Participants completed measures before and after ingesting a blinded beverage that contained either 0.8 g/kg alcohol or placebo administered in random order at each phase.

    “Participants completed measures before and after ingesting a blinded beverage that contained either 0.8 g/kg alcohol or placebo administered in random order at each phase.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Upon arrival, the participant completed self-report measures and engaged in objective breath tests to confirm compliance with recent alcohol abstinence.

    “Upon arrival, the participant completed self-report measures and engaged in objective breath tests to confirm compliance with recent alcohol abstinence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The few published test-retest studies of alcohol responses have included only brief between-session intervals with a focus on measurement reliability.

    “The few published test-retest studies of alcohol responses have included only brief between-session intervals with a focus on measurement reliability(30, 31).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [30] Mundt, 1997, Individual differences in alcohol responsivity: Physiological, psychomotor and subjective response domains, J Stud Alcohol source

      Not checked in the free run.

    • cites [31] Wilson, 1987, One-month repeatability of alcohol metabolism, sensitivity and acute tolerance, J Stud Alcohol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The DSM-IV criteria are similar to those in DSM-5 with the former including an item for alcohol-related legal problems that has since been dropped and excluding the DSM-5 item for craving that had not yet been developed.

    “The DSM-IV criteria are similar to those in DSM-5(8, 62) with the former including an item for alcohol-related legal problems that has since been dropped and excluding the DSM-5 item for craving that had not yet been developed.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] 2013

      Not checked in the free run.

    • cites [62] Hasin, 2013, DSM-5 criteria for substance use disorders: Recommendations and rationale, Am J Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    All these aforementioned effects remained after controlling for covariates and other risk factors, such as FH, and group differences were largely apparent on the rising and declining limbs as well as at peak BrAC.

    “All these aforementioned effects remained after controlling for covariates and other risk factors, such as FH, and group differences were largely apparent on the rising and declining limbs as well as at peak BrAC.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Altering euphoric and pleasurable effects of alcohol is hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene.

    “The findings may have relevance to medication development, as altering euphoric and pleasurable effects of alcohol would be important targets for novel treatments and are hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene(67–76).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [67] Anton, 2006, Combined pharmacotherapies and behavioral interventions for alcohol dependence: The COMBINE study: A randomized controlled trial, JAMA source

      Not checked in the free run.

    • cites [68] Drobes, 2004, Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment-seeking alcoholics and social drinkers, Alcohol Clin Exp Res source

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    • cites [69] Garbutt, 1999, Pharmacological treatment of alcohol dependence: A review of the evidence, JAMA source

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    • cites [70] Mason, 1999, A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence, Arch Gen Psychiatry source

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    • cites [71] Swift, 1995, Effect of naltrexone on human alcohol consumption, J Clin Psychiatry

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    • cites [72] Volpicelli, 1995, Effect of naltrexone on alcohol “high” in alcoholics, Am J Psychiatry source

      Not checked in the free run.

    • cites [73] King, 1997, Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence, Psychopharmacology (Berl) source

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    • cites [74] Swift, 1994, Naltrexone-induced alterations in human ethanol intoxication, Am J Psychiatry source

      Not checked in the free run.

    • cites [75] Anton, 2004, Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: Temporal effects of drinking, Psychopharmacology (Berl) source

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    • cites [76] Ray, 2007, Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: A double-blind placebo-controlled study, Arch Gen Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    While there are multiple pathways to development of a disorder as complex as AUD, maintenance of alcohol stimulatory and rewarding effects may play an important role in the continuation and progression of alcohol addiction.

    “While there are multiple pathways to development of a disorder as complex as AUD, maintenance of alcohol stimulatory and rewarding effects may play an important role in the continuation and progression of alcohol addiction.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol.

    “Limitations included that the reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol(18)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Koob, 2001, Drug addiction, dysregulation of reward, and allostasis, Neuropsychopharmacology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Koob and colleagues have coined the later stage of addiction as 'the dark side of addiction' because it is characterized by development of reward insensitivity and drinking behaviors related to negative reinforcement.

    “Koob and colleagues have coined the later stage of addiction as “the dark side of addiction”(65) because it is characterized by development of reward insensitivity and drinking behaviors related to negative reinforcement.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Koob, 2005, Plasticity of reward neurocircuitry and the ’dark side’ of drug addiction, Nat Neurosci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Trajectory analyses resulted in unequal subgroup sample sizes.

    “Further, trajectory analyses resulted in unequal subgroup sample sizes”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Beverages were consumed over a short interval to capture direct alcohol effects and minimize variability, but this may not translate to typical drinking situations.

    “beverages were consumed over short interval to capture direct alcohol effects and minimize variability but this may not translate to typical drinking situations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The present study includes one of the largest samples to date.

    “Thus, while the present study includes one of the largest samples to date and the only investigation of alcohol responses over time, replication will be a necessary next step to assure confidence in the main findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Participants under age 21 were not enrolled due to legal restrictions of alcohol administration in the U.S., precluding study of alcohol responses in earlier developmental periods.

    “participants under age 21 were not enrolled due to legal restrictions of alcohol administration in the U.S. precluding study of alcohol responses in earlier developmental periods.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Heavy drinkers have also shown reduced alcohol-related stimulation and ventral striatal brain activation relative to social drinkers.

    “However, heavy drinkers have also shown reduced alcohol-related stimulation and ventral striatal brain activation relative to social drinkers(82).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [82] Gilman, 2012, Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns, Neuropsychopharmacology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The results support prior work showing high alcohol-induced stimulation, reward, and craving in heavy drinkers or alcoholics as well as low alcohol-induced sedation and cortisol in other at-risk drinkers.

    “The results support prior work showing high alcohol-induced stimulation, reward, and craving in heavy drinkers or alcoholics(33, 79, 80) as well as low alcohol-induced sedation and cortisol in other at-risk drinkers(81).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [33] Roche, 2014, Acute alcohol response phenotype in heavy social drinkers is robust and reproducible, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [79] Ray, 2013, Subjective response to alcohol among alcohol-dependent individuals: Effects of the mu-opioid (OPRM1) gene and alcohol severity, Alcohol Clin Exp Res source

      Not checked in the free run.

    • cites [80] Thomas, 2004, Following alcohol consumption, nontreatment-seeking alcoholics report greater stimulation but similar sedation compared with social drinkers, J Stud Alcohol source

      Not checked in the free run.

    • cites [81] Schuckit, 1994, Low level of response to alcohol as a predictor of future alcoholism, Am J Psychiatry source

      Not checked in the free run.

46 of 46

  • The paper relies on this without support.

    The early phase of the allostasis model most closely matches a five-year interval in young adults.

    “The allostasis model’s early phase of addiction, which may most closely match a five-year interval in young adults, would be supported if alcohol reward sensitivity was maintained, and the later stage would be supported if reward sensitivity was diminished.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In humans, a dissociation has been found between 'liking' and 'wanting' for alcohol where small doses of alcohol cause spikes in 'wanting' yet leave 'liking' unaffected, and heavy drinkers show higher sensitivity to alcohol's stimulating and rewarding effects.

    “Similarly in humans, a dissociation has been found between ‘liking’ and ‘wanting’ for alcohol where small doses of alcohol cause spikes in ‘wanting’ yet leave ‘liking’ unaffected (Hobbs, Remington, & Glautier, 2005; Ostafin, Marlatt, & Troop-Gordon, 2010), and heavy drinkers show higher sensitivity to alcohol’s stimulating and rewarding effects (A. C. King, Hasin, O'Connor, McNamara, & Cao, 2016).”

    From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as A. C. King, Hasin, O'Connor, McNamara, & Cao, 2016

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Fridberg, 2014, Integrating alcohol challenge feedback in a brief intervention for young adult heavy drinker-smokers: A pilot study, Alcohol Clin Exp Res, 38

Cited by

Sorted by citations

Related

Authors
King, A. C., Hasin, D., O’Connor, S. J., McNamara, P. J., & Cao, D.
Affiliations
  • University of Chicago (US)
  • Columbia University (US)
  • Purdue University in Indianapolis (US)
  • University of Illinois Chicago (US)
Corresponding author
King, Andrea C.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2016-03
Volume
79
Issue
6
Pages
489-498
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2015.05.007
PMC
PMC4644521
OpenAlex
W1232293211
Semantic Scholar
fa803d290aac459f54e02209304659e2f93dcd77
Cited by
132
References
80
Citations by year
2026: 6 · 2025: 10 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 9 · 2020: 18 · 2019: 18 · 2018: 16 · 2017: 11 · 2016: 15 · 2015: 3
FWCI
11.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR001108)
  • National Institute on Alcohol Abuse and Alcoholism (R01AA013746, P60 AA07611-27, K05AA014223, P60AA007611)
  • National Cancer Institute (P30‐CA14599, P30CA014599)
  • National Center for Research Resources (UL1RR024999)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
alcoholism, heavy drinking, alcohol response, allostasis, incentive sensitization, alcohol reward, cortisol response, neuroendocrine response, alcohol tolerance, young adults
MeSH terms
Adult, Ethanol, Alcoholic Intoxication, Alcoholism, Double-Blind Method, Female, Humans, Hydrocortisone, Hypnotics and Sedatives, Male, Prospective Studies, Psychiatric Status Rating Scales, Reward, Young Adult

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