Background

Subjective responses (SRs) to alcohol have been implicated in alcoholism etiology, yet less is known about the latent factor structure of alcohol responses. The aim of this study was to examine the factor structure of SR using a battery of self-report measures during a controlled alcohol challenge.

Methods

Nontreatment seeking drinkers (N = 242) completed an intravenous alcohol challenge including the following SR measures: Biphasic Alcohol Effects Scale, Subjective High Assessment Scale, Profile of Mood States, Alcohol Urge Questionnaire, and single items assessing alcohol "Liking" and "Wanting." Ascending limb target breath alcohol concentrations were 0.02, 0.04, and 0.06, and descending limb target was 0.04 g/dl. Exploratory factor analyses were conducted separately on estimates of mean and dose responses on the ascending limb and on descending limb data. To examine the generalizability of this factor structure, these analyses were repeated in heavy drinkers (≥14 drinks/wk for men, ≥7 for women; n = 132) and light drinkers (i.e., nonheavy drinkers; n = 110).

Results

In the full sample, a 4-factor solution was supported for ascending limb mean and dose responses and descending limb data representing the following SR domains: Stimulation/Hedonia, Craving/Motivation, Sedation/Motor Intoxication, and Negative Affect. This 4-factor solution was replicated in heavy drinkers. In light drinkers, however, SR was better summarized by a 3-factor solution where ascending mean and descending limb responses consisted of Stimulation/Hedonia, Craving/Motivation, and a general negative valence factor, and dose responses consisted of a general positive valence factor, Sedation/Motor Intoxication, and Negative Affect.

Conclusions

These findings suggest that SR represents a multifaceted construct with consistent factor structure across both ascending and descending limbs. Further, as drinking levels escalate, more defined Craving/Motivation and negative valence dimensions may emerge. Longitudinal studies examining these constructs are needed to further our understanding of SR as potentially sensitive to alcohol-induced neuroadaptation.

Background

Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral striatal functional connectivity during alcohol-cue processing as a function of the A118G single-nucleotide polymorphism of the mu-opioid receptor (OPRM1) gene.

Methods

Seventeen individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional magnetic resonance imaging, while performing an alcohol taste-cues task. Psychophysiological interaction analyses investigated associations of the OPRM1 genotype with ventral and dorsal striatum functional connectivity, using the ventral striatum and the caudate as the seed region, respectively.

Results

Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i) greater activation of the insula and orbitofrontal cortex and (ii) stronger negative fronto-striatal functional connectivity for both ventral and dorsal striatal seed regions during processing of alcohol versus water cues.

Conclusions

These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.

Chronic cigarette smoking and polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) are associated with neurocognition in normal controls and those with various neuropsychiatric conditions. The influence of BDNF and COMT on neurocognition in alcohol dependence is unclear. The primary goal of this report was to investigate the associations of single nucleotide polymorphisms (SNPs) in BDNF Val66Met (rs6265) and COMT Val158Met (rs4680) with neurocognition in a treatment-seeking alcohol dependent cohort and determine if neurocognitive differences between non-smokers and smokers previously observed in this cohort persist when controlled for these functional SNPs. Genotyping was conducted on 70 primarily male treatment-seeking alcohol dependent participants (ALC) who completed a comprehensive neuropsychological battery after 33 ± 9 days of monitored abstinence. After controlling for COMT and BDNF genotypes, smoking ALC performed significantly worse than non-smoking ALC on the domains of auditory-verbal and visuospatial learning and memory, cognitive efficiency, general intelligence, processing speed, and global neurocognition. In smoking ALC, greater number of years of smoking over lifetime was related to poorer performance on multiple domains after controlling for genotypes and alcohol consumption. In addition, COMT Met homozygotes were superior to Val homozygotes on measures of executive skills and showed trends for higher general intelligence and visuospatial skills, while COMT Val/Met heterozygotes showed significantly better general intelligence than Val homozygotes. COMT Val homozygotes performed better than heterozygotes on auditory-verbal memory. BDNF genotype was not related to any neurocognitive domain. The findings are consistent with studies in normal controls and neuropsychiatric cohorts that reported COMT Met carriers demonstrated better performance on measures of executive skills and general intelligence. Results also indicated that the poorer performance of smoking compared to non-smoking ALC across multiple neurocognitive domains was not mediated by COMT or BDNF genotype. Overall, the findings lend support to the expanding clinical movement to make smoking cessation programs available to smokers at the inception of treatment for alcohol/substance use disorders.

Aims

To advance translational studies of the role of reward prediction error (PE) in alcohol use disorder, the present study sought to develop and conduct an initial test of an alcohol-specific PE task paradigm using functional magnetic resonance imaging in humans.

Methods

Alcohol dependent or social drinkers received small tastes of their preferred alcohol beverage or control beverage, with preceding visual cues indicating whether alcohol (or water) would be delivered. To assess both positive and negative PE signals, expectancies were systematically violated in both positive (i.e. expecting water and receiving alcohol) and negative (i.e. expecting alcohol and receiving water) directions. Exploratory trial-by-trial analyses were conducted to explore temporal fluctuations of activation within a priori-defined regions of interest that have been implicated in cue reactivity and PE processing.

Results

Across the entire sample of participants, positive PE-related brain activation was found in a large cluster comprised of frontal lobe regions, as well as insular cortex, and motor/sensory cortices. Compared to social drinking subjects, alcohol dependent subjects had greater positive PE-related brain activity in left superior parietal lobule, lateral occipital cortex and postcentral gyrus. Exploratory trial-by-trial analyses indicated differences in activation specific to type of taste, mostly at earlier trials.

Conclusions

This task-development oriented pilot study found that PE signaling may not be detected in expected brain regions when image analyses average across all PE trials of the task. Rather, a trial-by-trial analysis approach may help detect sparse, temporally distinct PE signaling in expected reward processing regions.

Short summary

This fMRI study of reward prediction error found greater positive prediction error-related activity (i.e. expecting water taste, receiving alcohol taste) in alcohol dependent individuals relative to social drinkers in parietal and occipital cortices. Trial-by-trial analyses may be able to better detect sparse prediction error signaling in expected reward processing regions.

Abstract Background The purpose of this research was to replicate a successful intervention to increase physical activity in a different region of the country, and explore genetic and physiological moderators of intervention efficacy drawn from a transdisciplinary theoretical framework. Method A randomized controlled trial comparing a print-based physical activity intervention (COSTRIDE) to a print-based health and wellness contact control (HW) intervention was conducted. Sedentary participants (n = 219) completed assessments at baseline and follow-up assessments at 3, 6, 9, and 12 months following the initiation of the intervention. Results Participants in both conditions significantly increased exercise behavior in the first six months, and then leveled off or decreased physical activity in the second six months of the study. Those in the COSTRIDE intervention increased significantly more than those in the HW intervention, and were better able to maintain their exercise behavior. Genetic factors (BDNF, rs6265; FTO, rs8044769), but not selected physiological (body temperature, blood lactate, systolic blood pressure, plasma norepinephrine, and heart rate) or subjective (perceived pain, affect) responses to physical activity, moderated response to the intervention. Conclusions There are underlying genetic factors that influence response to behavioral intervention, and a better understanding of these factors has the potential to influence the development, targeting and tailoring of behavioral interventions to increase physical activity. Trial registration Clinicaltrials.gov registration: NCT01091857.

Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned.