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1.
Psychopharmacology (Berl) ; 238(6): 1593-1607, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33660080

ABSTRACT

RATIONALE: Inhibition is a core executive function and refers to the ability to deliberately suppress attention, behavior, thoughts, and/or emotions and instead act in a specific manner. While acute alcohol exposure has been shown to impair response inhibition in the stop-signal and Go/NoGo tasks, reported alcohol effects on attentional inhibition in the Stroop task are inconsistent. Notably, studies have operationalized attentional inhibition variably and there has been intra- and inter-individual variability in alcohol exposure. OBJECTIVE: This study aimed to examine the acute effects of alcohol on attentional inhibition, considering previous limitations. METHODS: In a single-blind, cross-over design, 40 non-dependent participants with a medium-to-high risk drinking behavior performed a Counting Stroop task (CST) under a baseline and an arterial blood alcohol concentration (aBAC) clamp at 80 mg%. Attentional inhibition was assessed as the alteration of reaction times (RT), error rates (ER), and inverse efficiency scores (IES) between incongruent and congruent trials (interference score). Stroop performance was also assessed regardless of trial-type. RESULTS: Compared to saline, acute alcohol exposure via an aBAC clamp did not affect CST interference scores but increased RTs and IES in both incongruent and congruent trials. CONCLUSIONS: Attentional inhibition (Stroop interference score) was not impaired by clamped moderate alcohol exposure. Acute alcohol impaired Stroop performance evidenced by a general increase in response times. Our findings suggest that response and attentional inhibition do not share the same neurocognitive mechanisms and are affected differently by alcohol. Results could also be explained by automated behaviors known to be relatively unaffected by acute alcohol.


Subject(s)
Alcohol Drinking/psychology , Ethanol/pharmacology , Inhibition, Psychological , Adult , Attention/physiology , Blood Alcohol Content , Cross-Over Studies , Executive Function/physiology , Female , Humans , Male , Middle Aged , Reaction Time/drug effects , Single-Blind Method , Stroop Test
2.
Acta Psychiatr Scand ; 137(3): 252-262, 2018 03.
Article in English | MEDLINE | ID: mdl-29377059

ABSTRACT

OBJECTIVE: We investigated the potential of computer-based models to decode diagnosis and lifetime consumption in alcohol dependence (AD) from grey-matter pattern information. As machine-learning approaches to psychiatric neuroimaging have recently come under scrutiny due to unclear generalization and the opacity of algorithms, our investigation aimed to address a number of methodological criticisms. METHOD: Participants were adult individuals diagnosed with AD (N = 119) and substance-naïve controls (N = 97) ages 20-65 who underwent structural MRI. Machine-learning models were applied to predict diagnosis and lifetime alcohol consumption. RESULTS: A classification scheme based on regional grey matter attained 74% diagnostic accuracy and predicted lifetime consumption with high accuracy (r = 0.56, P < 10-10 ). A key advantage of the classification scheme was its algorithmic transparency, revealing cingulate, insular and inferior frontal cortices as important brain areas underlying classification. Validation of the classification scheme on data of an independent trial was successful with nearly identical accuracy, addressing the concern of generalization. Finally, compared to a blinded radiologist, computer-based classification showed higher accuracy and sensitivity, reduced age and gender biases, but lower specificity. CONCLUSION: Computer-based models applied to whole-brain grey-matter predicted diagnosis and lifetime consumption in AD with good accuracy. Computer-based classification may be particularly suited as a screening tool with high sensitivity.


Subject(s)
Alcohol Drinking , Alcoholism/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Gray Matter/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Image Processing, Computer-Assisted/methods , Machine Learning , Magnetic Resonance Imaging/methods , Adult , Aged , Alcohol Drinking/pathology , Alcoholism/pathology , Atrophy/pathology , Cerebral Cortex/pathology , Female , Gray Matter/pathology , Humans , Male , Middle Aged , Young Adult
3.
Transl Psychiatry ; 7(8): e1183, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28763064

ABSTRACT

Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol-dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol.


Subject(s)
Alcoholism/psychology , Conditioning, Operant/physiology , Delay Discounting/physiology , Impulsive Behavior/physiology , Adult , Alcohol Abstinence/psychology , Choice Behavior/physiology , Cues , Female , Humans , Male , Middle Aged , Neuropsychological Tests
5.
Pharmacogenomics J ; 11(5): 368-74, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20585342

ABSTRACT

In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.


Subject(s)
Alcohol Deterrents/therapeutic use , Alcoholism/drug therapy , Alcohols/metabolism , Atrial Natriuretic Factor/genetics , GATA4 Transcription Factor/genetics , Taurine/analogs & derivatives , Acamprosate , Adult , Alcoholism/genetics , Alcoholism/pathology , Atrial Natriuretic Factor/blood , Female , GATA4 Transcription Factor/metabolism , Gene Dosage , Genetic Association Studies , Genetic Variation , Humans , Linkage Disequilibrium , Male , Middle Aged , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Randomized Controlled Trials as Topic , Recurrence , Risk , Taurine/genetics , Taurine/therapeutic use
6.
J Psychopharmacol ; 24(2): 247-55, 2010 Feb.
Article in English | MEDLINE | ID: mdl-18957475

ABSTRACT

Stress is known to induce cigarette craving in smokers, but the underlying mechanisms are widely unknown. We investigated how dependence severity, smoking habits and stress-induced cortisol secretion are associated with increased cigarette craving after a standardised laboratory stressor. Hundred and six healthy participants (50 men, age 18-19 years) underwent a standardised public speaking stress task. In all, 35 smoked daily (DS), 13 smoked occasionally (OS), and 58 never smoked (NS). Smoking was unrestricted until 2 h before stress onset. Plasma cortisol was measured before and up to 95 min after the stressor. All current smokers rated intensity of cigarette craving immediately before and immediately after the stressor using the Brief Questionnaire of Smoking Urges (BQSU). Cortisol levels significantly increased in response to stress in all groups. The magnitude of this stress response was significantly lower in DS compared with OS and NS but did not differ between OS and NS. Baseline BQSU scores were significantly higher in DS than OS. BQSU scores increased significantly during the stress period and were positively correlated to the cortisol response in the DS but were unrelated to their nicotine dependence scores. In OS, no change in cigarette craving could be observed. In daily smokers, cigarette craving is increased after compared with before stress exposure and is related to the magnitude of cortisol stress response rather than to severity of nicotine dependence. This result supports, but does not prove, the concept that hypothalamus-pituitary-adrenal stimulation is one of the mechanisms how stress can elicit cigarette craving.


Subject(s)
Hydrocortisone/blood , Smoking/psychology , Stress, Psychological/metabolism , Tobacco Use Disorder/psychology , Adolescent , Behavior, Addictive/psychology , Female , Humans , Hypothalamo-Hypophyseal System/metabolism , Male , Pituitary-Adrenal System/metabolism , Severity of Illness Index , Speech , Surveys and Questionnaires , Young Adult
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