Stress, Endogenous Opioid Peptides, and the Reinforcement Value of Nicotine

Clinical Psycholog

Reduced executive and default network functional connectivity in cigarette smokers

Altered functional connectivity has been associated with acute and chronic nicotine use. Connectivity alterations, specifically in the right and left executive control networks (RECN/LECN) and the default mode network (DMN), may contribute to the addiction cycle. The objective of this study was to determine if executive control network (ECN) and DMN connectivity is different between non‐smokers and smokers and whether reductions in connectivity are related to chronic cigarette use. The RECN, LECN, and DMN were identified in resting state functional magnetic resonance imaging data in 650 subjects. Analyses tested for group differences in network connectivity strength, controlling for age and alcohol use. There was a significant group effect on LECN and DMN connectivity strength with smokers (n = 452) having lower network strengths than non‐smokers (n = 198). Smokers had lower connectivity than non‐smokers associated with key network hubs: the dorsolateral prefrontal cortex, and parietal nodes within ECNs. Further, ECN connectivity strength was negatively associated with pack years of cigarette use. Our data suggest that chronic nicotine use negatively impacts functional connectivity within control networks that may contribute to the difficulty smokers have in quitting. Hum Brain Mapp 36:872–882, 2015. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110754/1/hbm22672.pd

Reduced Left Executive Control Network Functional Connectivity Is Associated with Alcohol Use Disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108693/1/acer12505.pd

Effects of naltrexone on cortisol levels in heavy drinkers

The primary objectives of this study were to: (a) examine the neuroendocrine effects of naltrexone vs. placebo by comparing serum cortisol levels; and (b) test the biobehavioral correlates of naltrexone-induced changes in cortisol. Non-treatment seeking heavy drinkers (n = 37) completed two intravenous alcohol administrations, one after naltrexone (50 mg) and one after placebo. Cortisol levels were measured at baseline and after alcohol intake (BrAC = 0.06 g/dl) on both sessions, as were subjective responses to alcohol. Analyses revealed that naltrexone significantly raised overall cortisol levels compared to placebo. Cortisol levels decreased during alcohol administration and a stronger decrease was observed in the naltrexone condition. Cortisol levels were, in turn, inversely related to some of alcohol's the reinforcing effects (i.e., alcohol 'high,' vigor) and positively associated with some of its unpleasant effects (i.e., sedation and subjective intoxication). These results suggest that naltrexone alters cortisol levels in heavy drinkers and that its effects on subjective responses to alcohol may be related, in part, to naltrexone's ability to activate the HPA-axis

Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention

Alcohol use disorder (AUD) is a devastating public health problem in which both genetic and environmental factors play a role. Growing evidence supports that epigenetic regulation is one major mechanism in neuroadaptation that contributes to development of AUD. Meanwhile, epigenetic patterns can be modified by various stimuli including exercise. Thus, it is an intriguing question whether exercise can lead to methylation changes that are opposite to those related to drinking. We herein conducted a comparative study to explore this issue. Three cohorts were profiled for DNA methylation (DNAm), including a longitudinal exercise intervention cohort (53 healthy participants profiled at baseline and after a 12-months exercise intervention), a cross-sectional case-control cohort (81 hazardous drinkers and 81 healthy controls matched in age and sex), and a cross-sectional binge drinking cohort (281 drinkers). We identified 906 methylation sites showing significant DNAm differences between drinkers and controls in the case-control cohort, as well as, associations with drinking behavior in the drinking cohort. In parallel, 341 sites were identified for significant DNAm alterations between baseline and follow-up in the exercise cohort. Thirty-two sites overlapped between these two set of findings, of which 15 sites showed opposite directions of DNAm associations between exercise and drinking. Annotated genes of these 15 sites were enriched in signaling pathways related to synaptic plasticity. In addition, the identified methylation sites significantly associated with impaired control over drinking, suggesting relevance to neural function. Collectively, the current findings provide preliminary evidence that exercise has the potential to partially reverse DNAm differences associated with drinking at some CpG sites, motivating rigorously designed longitudinal studies to better characterize epigenetic effects with respect to prevention and intervention of AUD

The Effects of Exercise Duration and Intensity on Breast Cancer-Related DNA Methylation: A Randomized Controlled Trial

Emerging research suggests that one mechanism through which physical activity may decrease cancer risk is through its influence on the methylation of genes associated with cancer. The purpose of the current study was to prospectively test, using a rigorous experimental design, whether aerobic exercise affects DNA methylation in genes associated with breast cancer, as well as whether quantity of exercise completed affects change in DNA methylation in a dose-response manner. 276 women (M age = 37.25, SD = 4.64) were recruited from the Denver metro area for a randomized controlled trial in which participants were assigned to a supervised aerobic exercise program varying in a fully crossed design by intensity (55-65% versus 75-85% of VO2max) and duration (40 versus 20 min per session). DNA methylation was assessed via blood samples provided at baseline, after completing a 16-week supervised exercise intervention, and six months after the intervention. 137 participants completed the intervention, and 81 had viable pre-post methylation data. Contrary to our hypotheses, total exercise volume completed in kcal/kg/week was not associated with methylation from baseline to post-intervention for any of the genes of interest. An increase in VO2max over the course of the intervention, however, was associated with decreased post-intervention methylation of BRCA1, p = 0.01. Higher levels of self-reported exercise during the follow-up period were associated with lower levels of GALNT9 methylation at the six-month follow-up. This study provides hypothesis-generating evidence that increased exercise behavior and or increased fitness might affect methylation of some genes associated with breast cancer to reduce risk. &nbsp;</p

The New Runner's High? Examining Relationships Between Cannabis Use and Exercise Behavior in States With Legalized Cannabis

Scientific literature examining cannabis use in the context of health behaviors, such as exercise engagement, is extremely sparse and has yielded inconsistent findings. This issue is becoming increasingly relevant as cannabis legalization continues, a situation that has been associated with increased initiation of use among adults, and increased potency of available products in legalized states. Physical activity is among the most important health behaviors, but many Americans do not meet minimum exercise recommendations for healthy living. Common issues surrounding low exercise rates include inadequate enjoyment of and motivation to exercise, and poor recovery from exercise. It is unclear whether cannabis use shortly before and/or after exercise impacts these issues, and whether this co-use affects exercise performance. The present online survey study examines attitudes and behaviors regarding cannabis use with exercise among adult cannabis users living in states with full legal access (N = 605). Results indicated that the majority (81.7%) of participants endorsed using cannabis concurrently with exercise, and those who did tended to be younger and more likely to be males (p &lt; 0.0005 for both). Even after controlling for these differences, co-users reported engaging in more minutes of aerobic and anaerobic exercise per week (p &lt; 0.01 and p &lt; 0.05, respectively). In addition, the majority of participants who endorsed using cannabis shortly before/after exercise reported that doing so enhances their enjoyment of and recovery from exercise, and approximately half reported that it increases their motivation to exercise. This study represents an important step in clarifying cannabis use with exercise among adult users in states with legal cannabis markets, and provides guidance for future research directions

Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems

The New Runner's High? Examining Relationships Between Cannabis Use and Exercise Behavior in States With Legalized Cannabis

Scientific literature examining cannabis use in the context of health behaviors, such as exercise engagement, is extremely sparse and has yielded inconsistent findings. This issue is becoming increasingly relevant as cannabis legalization continues, a situation that has been associated with increased initiation of use among adults, and increased potency of available products in legalized states. Physical activity is among the most important health behaviors, but many Americans do not meet minimum exercise recommendations for healthy living. Common issues surrounding low exercise rates include inadequate enjoyment of and motivation to exercise, and poor recovery from exercise. It is unclear whether cannabis use shortly before and/or after exercise impacts these issues, and whether this co-use affects exercise performance. The present online survey study examines attitudes and behaviors regarding cannabis use with exercise among adult cannabis users living in states with full legal access (N = 605). Results indicated that the majority (81.7%) of participants endorsed using cannabis concurrently with exercise, and those who did tended to be younger and more likely to be males (p &lt; 0.0005 for both). Even after controlling for these differences, co-users reported engaging in more minutes of aerobic and anaerobic exercise per week (p &lt; 0.01 and p &lt; 0.05, respectively). In addition, the majority of participants who endorsed using cannabis shortly before/after exercise reported that doing so enhances their enjoyment of and recovery from exercise, and approximately half reported that it increases their motivation to exercise. This study represents an important step in clarifying cannabis use with exercise among adult users in states with legal cannabis markets, and provides guidance for future research directions.</p

Brain volumes in alcohol use disorder : Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxelbased, multi-tissue mega-analytic approach, thereby extending our recent surfacebased region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller groupby- sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD