Search

Background and Aims: The brain age gap (BAG), calculated as the difference between a machine learning model‐based predicted brain age and chronological age, has been increasingly investigated in psychiatric disorders. Tobacco and alcohol use are associated with increased BAG; however, no studies have compared global and regional BAG across substances other than alcohol and tobacco. This study aimed to compare global and regional estimates of brain age in individuals with substance use disorders and healthy controls. Design: This was a cross‐sectional study. Setting: This is an Enhancing Neuro Imaging through Meta‐Analysis Consortium (ENIGMA) Addiction Working Group study including data from 38 global sites. Participants: This study included 2606 participants, of whom 1725 were cases with a substance use disorder and 881 healthy controls. Measurements: This study used the Kaufmann brain age prediction algorithms to generate global and regional brain age estimates using T1 weighted magnetic resonance imaging (MRI) scans. We used linear mixed effects models to compare global and regional (FreeSurfer lobestrict output) BAG (i.e. predicted minus chronological age) between individuals with one of five primary substance use disorders as well as healthy controls. Findings Alcohol use disorder (β = −5.49, t = −5.51, p < 0.001) was associated with higher global BAG, whereas amphetamine‐type stimulant use disorder (β = 3.44, t = 2.42, p = 0.02) was associated with lower global BAG in the separate substance‐specific models. Conclusions: People with alcohol use disorder appear to have a higher brain‐age gap than people without alcohol use disorder, which is consistent with other evidence of the negative impact of alcohol on the brain. [ABSTRACT FROM AUTHOR]

Objective: Conflicting evidence exists regarding the effects of cannabis on alcohol consumption, with some studies suggesting that cannabis is a substitute for alcohol, whereas others suggest that cannabis complements alcohol, thereby increasing drinking. Cannabidiol (CBD) has shown preclinical promise in decreasing alcohol consumption. This study explores the effects of cannabis containing different potencies of CBD and delta-9-tetrahydrocannabinol (THC) on alcohol consumption. Method: In this naturalistic observational study, 120 cannabis and alcohol-using adults (mean age = 33.2 years, 39.2% female, 83.3% white) were assigned to use one of three legal-market cannabis strains (predominantly THC, predominantly CBD, and CBD + THC) ad libitum for 5 days. Timeline Followback data on drinking and cannabis use were collected at a baseline session pertaining to the 30 days prior to the ad libitum period, and data regarding alcohol and cannabis use during the 5-day period were collected at follow-up (FU), immediately following the 5-day period. Results: Regression models tested strain differences in drinking outcomes during the ad libitum period. Orthogonal contrast codes were created comparing the CBD group with the other two groups and comparing the THC group with the CBD + THC group. The CBD group drank fewer drinks per drinking day (p < .05), had fewer alcohol use days (p < .05), and fewer alcohol and cannabis co-use days (p < .05) compared with the other groups. No differences emerged between the THC and the CBD + THC group. Conclusions: Cannabinoid content should be considered in studies of alcohol and cannabis co-use. Findings are consistent with preclinical work, suggesting that CBD may be associated with decreased alcohol consumption. [ABSTRACT FROM AUTHOR]

The most common causes of morbidity and mortality in the western world can be accounted for by unhealthy patterns of behavior (e.g. smoking, sedentary lifestyle, unhealthy diet, and alcohol consumption). Interventions to improve health behavior are sorely needed. To fully realize the potential of health behavior change interventions, be they individual level, community level, social structural, or policy-based, a greater understanding of the extent to which genomics can inform efforts at health behavior change is warranted. In this commentary, we explore three relatively novel possible routes to the integration of genomics and health behavior: (1) genomics may influence health behavior indirectly through intermediate phenotypes, requiring well-defined theory-based and mechanistic models of health behavior, (2) genomics may moderate response to interventions to change health behavior, and (3) genomics, specifically epigenetic variation, may be influenced by health behavior. The integration of genomics into research on interventions to change health behavior is not without challenges and will certainly require transdisciplinary collaborative science to succeed. We provide specific action points for moving the science forward to explore the extent to which genomic information can be harnessed to ultimately decrease morbidity and mortality associated with unhealthy behavior., (Copyright © 2012 S. Karger AG, Basel.)

Gamma-aminobutyric acid A (GABA(A)) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have shown an association between the gene for the alpha2-subunit of the GABA(A) receptor (GABRA2) and alcoholism. In the present study, we examined the functional relevance of the GABRA2 gene in alcohol dependence by assessing brain GABRA2 mRNA and GABA(A)alpha2-subunit protein levels in post-mortem prefrontal cortical tissue collected from control and alcohol-dependent individuals. In addition, using an endophenotype approach, we tested whether the GABRA2 gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms (rs573400, rs279871 and rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 x breath alcohol concentration on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, reanalysis of a previous intravenous alcohol administration study confirmed the results of the oral alcohol challenge study. In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.

Rationale: Haloperidol, a D2 antagonist, has been shown to moderate the effects of alcohol consumption on craving., Objective: The present study was designed to determine whether a single 5-mg dose of olanzapine (a D2/5-HT2 antagonist) would influence responses to alcohol cues or an alcohol challenge. It was hypothesized that olanzapine would attenuate cue-elicited urge to drink, attenuate the effects of alcohol consumption on urge to drink, and reduce the rewarding effects of alcohol., Methods: To test these hypotheses, 26 heavy social drinkers were randomized to receive either 5 mg olanzapine or placebo approximately 8 h before each of two experimental sessions. Participants consumed a moderate dose of alcohol in one experimental session and a non-alcohol control beverage in another session., Results: Results indicated that mere exposure to alcohol cues and consumption of alcohol increased urge to drink and that olanzapine attenuated these effects. Results also indicated that alcohol increased subjective stimulation and high while olanzapine did not moderate these effects., Conclusions: These results suggest that olanzapine did not influence the rewarding effects of alcohol but did attenuate the effects of alcohol cues and an alcohol challenge on urge to drink.

The purpose of this study was to conduct a content analysis of smoking craving in order to investigate more precisely the subjective nature of the construct with the goal of informing assessment. Thirty-two smokers interested in cessation treatment provided free response written descriptions of the level of craving they normally experience. These responses were analyzed for subjective content along five theoretical domains: physiological, affective, cognitive, behavioral, and synonyms (of craving). Although there were no differences in the relative proportion of broad content terms smokers used to describe their craving (e.g., cognitive versus affective), this analysis revealed considerable diversity in the specific terms smokers used. Some smokers described their craving in purely physiological terms whereas others used primarily cognitive terms, and still others used affective terms. To assume that smoking craving is qualitatively similar across persons, then, may mask important variations that define the individual experience of craving.

The mechanisms of naltrexone's effects on urges to drink during abstinence are unclear. Naltrexone may suppress either urges to drink specifically or appetitive responses in general. The effects of naltrexone on cue reactivity to alcoholic and sweet nonalcoholic beverages were investigated. Alcohol-dependent men (N = 53) in treatment received naltrexone (50 mg) or placebo. Four hours later, they received baseline assessment, exposure to fruit juice, and exposure to their usual alcoholic beverage in 3-min trials. Naltrexone reduced urge to drink and self-reported attention to the alcohol cues, not at the initial exposure but after repeated exposures to alcohol cues. Naltrexone reduced negative affect across baseline and alcohol trials. No effects of naltrexone on responses to the nonalcoholic appetitive beverage cues were found, suggesting that general appetite suppression does not mediate the effects of naltrexone on urges.

Urge to drink ("craving") has been a central focus of many theories and treatments, but some researchers question the importance of urges during recovery. Several studies assessed reactions to the presence of beverage alcohol (cue-reactivity) or to simulated high-risk situations (role plays). Higher urges in response to role plays predicted more drinking during the 6 months after treatment. However, urges in response to beverage cues were inconsistently predictive of outcome while measures of awareness or attention to cues predicted less drinking. Urge to drink might reflect a conflict between motivation to drink and awareness of danger. Whether urges predict increased risk of drinking should be a function of factors that affect motivation to drink, awareness of risk and effectiveness of coping. Cue-reactivity assessment has recently been used to bridge the gap between psychosocial and biomedical approaches in several ways: (1) salivation to cues predicts increased drinking independent of urge or attention, showing the value of including both physiological and psychosocial measures; (2) naltrexone has been shown to decrease cue-elicited urge to drink, illustrating the value of this assessment methodology for medications evaluation and (3) pre-pulse inhibition of startle response is being used to investigate the role of dopaminergic pathways in cue-elicited urge. Thus, this laboratory based program of research has the potential to add to knowledge of both biomedical and psychosocial mechanisms involved in urge and relapse, leading to greater integration of models.

Rationale: Several previous investigations with animals and humans have suggested that nicotine enhances prepulse inhibition of the startle reflex (PPI). However, the administration of nicotine activates mesolimbic dopamine, and activation of mesolimbic dopamine is known to attenuate prepulse inhibition of the startle reflex (PPI), which might suggest that nicotine would decrease PPI., Objective: The primary aim of this study was to test rigorously the effects of smoking high nicotine cigarettes on PPI and other measures (e.g., heart rate, craving, and mood) when the concentration of nicotine peaks in the brain (i.e., immediately after smoking)., Methods: Thirty smokers participated in two experimental sessions 1 week apart. Two high nicotine cigarettes were smoked in one session, and two control cigarettes were smoked in the other session after overnight deprivation., Results: The results indicated that smoking the high nicotine cigarettes decreased PPI and that PPI increased across trials in both conditions. The interaction between nicotine dose and trial was not significant, although it appeared that high nicotine may have reversed an increase in PPI across trials in the control condition. High nicotine cigarettes also significantly increased heart rate, decreased the latency to peak startle response on control trials, but did not alter the magnitude of the startle response., Discussion: The findings suggest that either high nicotine cigarettes reduced PPI, or possibly, that high nicotine cigarettes may have reversed an increase in PPI across trials as evident in the control condition.

The aim of the present study was to examine the relationship between measures of novelty and sensation seeking and both psychophysiological and subjective measures of stimulation after a pharmacological challenge with an indirect dopamine agonist, d-amphetamine. Prepulse inhibition (PPI) of the startle reflex and subjective responses were assessed after the challenge. The results indicated that the Novelty Seeking scale of the Tridimensional Personality Questionnaire (TPQ; M. Zuckerman, 1994). TPQ was a significant predictor of lower PPI and greater subjective stimulation. The Disinhibition scale of the Sensation Seeking Scale (SSS; M. Zuckerman, S. B. G. Eysenck, & M. J. Eysenck, 1978) moderated the effects of amphetamine on stimulation and elation, whereas the Boredom Susceptibility and Experience Seeking subscales of the SSS moderated subjective stimulation. These findings indicate that higher scores on novelty and sensation seeking correspond to heightened sensitivity to the effects of a stimulant medication.

The present study investigated whether exposure to smoking cues would attenuate prepulse inhibition (PPI) of the startle reflex and increase craving among smokers across 2 experimental sessions. It was hypothesized that exposure to smoking cues would result in a decrease in PPI. Twenty-six smokers were exposed to smoking cues and control cues in 2 experimental sessions 1 week apart. Results indicate that smoking cues reliably attenuated PPI in both the 1st and 2nd sessions as compared with control cues. Findings also suggest that smoking cues reliably increased craving, increased negative affect, and reduced positive affect relative to baseline measures in both sessions. Results are consistent with the premise that exposure to smoking cues precipitates increases in dopamine activation or changes in information processing that cause a disruption of PPI.

Background: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high-risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory-based, cue-elicited urge to drink among abstinent alcoholics in treatment., Methods: Alcohol-dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After approximately 1 week on medication, all received cue reactivity assessment., Results: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue-elicited decreases in heart rate were not affected by the medication., Conclusions: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments.

The body responds to stress through a hormone system called the hypothalamic-pituitary-adrenal (HPA) axis. Stimulation of this system results in the secretion of stress hormones (i.e., glucocorticoids). Chronic excessive glucocorticoid secretion can have adverse health effects, such as Cushing's syndrome. Alcohol intoxication activates the HPA axis and results in elevated glucocorticoid levels. Ironically, elevated levels of these stress hormones may contribute to alcohol's pleasurable effects. With chronic alcohol consumption, however, tolerance may develop to alcohol's HPA axis-activating effects. Chronic alcohol consumption, as well as chronic glucocorticoid exposure, can result in premature and/or exaggerated aging. Furthermore, the aging process affects a person's sensitivity to alcohol and HPA axis function. Thus, a three-way interaction exists among alcohol consumption, HPA axis activity, and the aging process. The aging process may impair the HPA axis' ability to adapt to chronic alcohol exposure. Furthermore, HPA axis activation may contribute to the premature or exaggerated aging associated with chronic alcohol consumption.

The present study was designed to examine the effects of a low dose of alcohol on prepulse inhibition (PPI) of the startle response and self-report measures of affect. Eighteen subjects participated in a counterbalanced repeated-measures design in which they received a beverage with alcohol during one session and a nonalcohol beverage during a different experimental session. The startle response was probed in two separate 10-min blocks immediately after consumption of the alcohol. Although alcohol significantly suppressed the startle response in general, it did not do so to an extent that compromised detection of PPI. The effects of alcohol on PPI were primarily evident in the first block and were dependent on baseline levels of PPI, such that alcohol resulted in a reduction of PPI in subjects who demonstrated low PPI at baseline and an increase in PPI for subjects with high PPI at baseline. Alcohol also significantly increased self-reported stimulation during the first block and increased negative affect during the second block. These findings suggest that baseline PPI may reflect an important individual difference that is predictive of the direction and magnitude of alcohol-induced changes in sensorimotor gating.

Research has demonstrated that smoking during pregnancy has deleterious effects on the health of the unborn child as well as the mother. The present study examined whether pregnant smokers would have a greater intention to quit smoking, whether the stage of pregnancy would influence the intention to quit, and whether variables which have predicted cessation among pregnant smokers would also predict intention to quit. The results indicated that pregnant women did not have a significantly greater intention to quit smoking compared to nonpregnant smokers, despite the health risks to their child. Women who were further along in their pregnancy and women who smoked more cigarettes on a daily basis demonstrated the least intention to quit. Notably, women in the first trimester showed the greatest intention to quit, suggesting that pregnant women may be most receptive to quitting during their first trimester.