Irregular Autonomic Modulation Predicts Risky Drinking and Altered Ventromedial Prefrontal Cortex Response to Stress in Alcohol Use Disorder

2021 ◽  
Author(s):  
Seungju Hwang ◽  
Jorge S Martins ◽  
Ryan J Douglas ◽  
Justin J Choi ◽  
Rajita Sinha ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Block Design ◽  
Approximate Entropy ◽  
Ventromedial Prefrontal Cortex ◽  
Risky Drinking ◽  
Social Drinkers ◽  
Response To Stress ◽  
Electrocardiogram Ecg

Abstract Aims Autonomic dysfunction has been associated with risky drinking and alcohol use disorder (AUD). Although autonomic nervous system (ANS) activity has been attributed to the ventromedial prefrontal cortex (VmPFC)-limbic-striatal regions, the specific role of ANS disruption in AUD and its association with these regions remain unclear. Using functional magnetic resonance imaging (fMRI) and concurrent electrocardiogram (ECG), the current study examined neural correlates of ANS activity in AUD and its role in AUD pathology. Methods Demographically matched 20 AUD patients and 20 social drinkers (SD) completed an fMRI task involving repeated exposure to stress, alcohol-cue and neutral-relaxing images in a block design. Based on the known VmPFC-limbic-striatal functions involved in emotions, reward and the ANS, we performed a regions of interest (ROI) analysis to examine the associations between ANS activity and neural responses in the VmPFC, amygdala, and ventral striatum. Results Across conditions, AUD patients showed significantly higher levels of overall heart rate (HR) and approximate entropy (ApEn) compared to SD (Ps < 0.05). In all participants, increased HR was associated with greater drinking volume (P < 0.05). In addition, higher ApEn levels were associated with greater drinking volume (P < 0.05) and decreased right VmPFC response to stress (P < 0.05). Discussion Our findings demonstrate ANS disruption in AUD indexed by high overall HR and ApEn. The association between ApEn and rVmPFC response suggests that ApEn may play a role in modulating drinking via interactions with neural regions of emotion regulation. These findings provide insight into patterns of ANS disruption and their relevance to AUD pathology.

scholarly journals An Initial Investigation of Disrupted Intracortical Myelin as a Novel Brain Marker of Alcohol Use Disorder

2020 ◽  
Author(s):  
Vanessa Morris ◽  
Luciano Minuzzi ◽  
Nicholas Bock ◽  
James MacKillop ◽  
Michael Amlung
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Gray Matter ◽  
Alcohol Use Disorder ◽  
A Priori ◽  
Anterior Cingulate ◽  
Posterior Cingulate ◽  
Cohen’S D ◽  
Cohen's D

Abstract: Although disruption of cortical gray matter and white matter tracts are well-established markers of alcohol use disorder (AUD), this is the first study to examine the specific role of intracortical myelin (ICM; i.e., highly myelinated gray matter in deeper cortical layers) in AUD. The current study used a 3T MRI sequence optimized for high intracortical contrast to examine patterns of ICM-related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Secondary aims included exploring continuous associations with alcohol problem severity and examining sex differences. Surface-based analytic techniques were used to quantify ICM-related MRI signal for a priori region of interest analyses (20 bilateral regions) and exploratory vertex-wise analyses (using Cohen’s d). Although the distribution of ICM-related signal was generally comparable between groups, the AUD group exhibited significantly (p<.05) greater ICM-related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, dorsolateral prefrontal cortex, and posterior cingulate, among other regions (Cohen’s d = .50-.75, indicating medium magnitude effects). Significant positive correlations between ICM signal and AUD severity were found in several frontal, parietal, cingulate, and temporal regions (rs .25-.34). No sex differences in ICM were observed. These findings provide initial proof-of-concept for examining ICM in relation to AUD. Understanding the pathophysiological mechanisms of these associations (e.g., neuroinflammation) and the clinical relevance of ICM is warranted.

scholarly journals Prefrontal cortex eQTLs/mQTLs enriched in genetic variants associated with alcohol use disorder and other diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 789-800
Author(s):  
Honghuang Lin ◽  
Fan Wang ◽  
Andrew J Rosato ◽  
Lindsay A Farrer ◽  
David C Henderson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Genetic Variants ◽  
Alcohol Use Disorder ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Genome Wide ◽  
Morphine Addiction ◽  
Methylation Patterns ◽  
Methylation Quantitative Trait Loci

Aim: This study aimed to investigate the function of genome-wide association study (GWAS)-identified variants associated with alcohol use disorder (AUD)/comorbid psychiatric disorders. Materials & methods: Genome-wide genotype, transcriptome and DNA methylome data were obtained from postmortem prefrontal cortex (PFC) of 48 Caucasians (24 AUD cases/24 controls). Expression/methylation quantitative trait loci (eQTL/mQTL) were identified and their enrichment in GWAS signals for the above disorders were analyzed. Results: PFC cis-eQTLs (923 from cases+controls, 27 from cases and 98 from controls) and cis-mQTLs (9,932 from cases+controls, 264 from cases and 695 from controls) were enriched in GWAS-identified genetic variants for the above disorders. Cis-eQTLs from AUD cases were mapped to morphine addiction-related genes. Conclusion: PFC cis-eQTLs/ cis-mQTLs influence gene expression/DNA methylation patterns, thus increasing the disease risk.

scholarly journals Identifying alcohol problems among suicide attempters visiting the emergency department

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinhee Lee ◽  
Seongho Min ◽  
Joung-Sook Ahn ◽  
Hyun Kim ◽  
Yong-Sung Cha ◽  
...  
Keyword(s):  
Emergency Department ◽  
Alcohol Use ◽  
Biochemical Markers ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Alcohol Problems ◽  
Self Report ◽  
Risky Drinking ◽  
Psychiatric Interview ◽  
Suicide Attempters

Abstract Background Many suicide attempters brought to our emergency department (ED) have been found to have alcohol problems, and this should be taken serious consideration because alcohol use disorder is a risk factor for suicide reattempt. In this study, we aimed to estimate the effectiveness of alcohol-related biochemical markers and Alcohol Use Disorder Identification Test Consumption (AUDIT-C) in suicide attempters who visited our ED based on the gold standard for clinical diagnosis used by psychiatrists for alcohol use disorder. Moreover, we aimed to search for a significant standard when clinicians make correct predictions about alcohol use disorder using these markers. Methods Among the subjects who visited ED following a suicide attempt, a total of 203 subjects were selected. Following a psychiatric interview, the subjects who met the criteria for alcohol abuse or alcohol dependence according to DSM-IV-TR in the past year were defined as the “alcohol use disorder” group. Although some subjects did not meet these criteria, men with a weekly alcohol intake of ≥14 drinks and women with a weekly alcohol intake of ≥7 drinks were classified as the “risky drinking” group. AUDIT-C was used as a self-report; further, aspartate aminotransferase, gamma-glutamyltransferase (GGT), and carbohydrate-deficient transferrin (CDT) were assayed using standard methods, and GGT–CDT was calculated using this formula: 0.8 × ln(GGT) + 1.3 × ln(%CDT). Results In total, 88 subjects met the criteria for alcohol use disorder and 115 were included in the reference group. In the screening for alcohol use disorder, the AUC of AUDIT-C was 0.89 for men and 0.87 for women. In the screening for risky drinking, the AUC of AUDIT-C was 0.99 for men and 0.93 for women. Compared with other biochemical markers, AUDIT-C showed the highest AUC value for screening for both alcohol use disorder and risky drinking, with the trend being more prominent in men. Conclusions Among the biochemical markers, AUDIT-C yielded the highest sensitivity, specificity, and accuracy in diagnosing alcohol use disorder among suicide attempters in ED. Comparison of results revealed that the use of AUDIT-C with biochemical markers or its use alone can help screen for alcohol use disorder or risky drinking in clinical settings.

scholarly journals Lower Choline Rate in the Left Prefrontal Cortex Is Associated With Higher Amount of Alcohol Use in Alcohol Use Disorder

2018 ◽  
Vol 9 ◽  
Author(s):  
Rodrigo Stênio Moll de Souza ◽  
Marcos Rosa ◽  
Thaísa Malbar Rodrigues ◽  
Thayssa Dalla Costa Escobar ◽  
Emerson Leandro Gasparetto ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Alcohol Use Disorder

scholarly journals Human Plasma BDNF Is Associated With Amygdala-Prefrontal Cortex Functional Connectivity and Problem Drinking Behaviors

2019 ◽  
Vol 23 (1) ◽  
pp. 1-11
Author(s):  
Stephanie M Gorka ◽  
Tara Teppen ◽  
Milena Radoman ◽  
K Luan Phan ◽  
Subhash C Pandey
Keyword(s):  
Prefrontal Cortex ◽  
Individual Differences ◽  
Functional Connectivity ◽  
Alcohol Use ◽  
Medial Prefrontal Cortex ◽  
Neurotrophic Factor ◽  
Alcohol Use Disorder ◽  
Brain Derived Neurotrophic Factor ◽  
Drinking Behaviors ◽  
Threat Of Shock

Abstract Background Preclinical studies suggest that decreased levels of brain-derived neurotrophic factor in the amygdala play a role in anxiety and alcohol use disorder. The association between brain-derived neurotrophic factor levels and amygdala function in humans with alcohol use disorder is still unclear, although neuroimaging studies have also implicated the amygdala in alcohol use disorder and suggest that alcohol use disorder is associated with disrupted functional connectivity between the amygdala and prefrontal cortex during aversive states. Methods The current study investigated whether plasma brain-derived neurotrophic factor levels in individuals with and without alcohol use disorder (n = 57) were associated with individual differences in amygdala reactivity and amygdala-prefrontal cortex functional connectivity during 2 forms of aversive responding captured via functional magnetic resonance imaging: anxiety elicited by unpredictable threat of shock and fear elicited by predictable threat of shock. We also examined whether brain-derived neurotrophic factor and brain function were associated with binge drinking episodes and alcohol use disorder age of onset. Results During anxiety, but not fear, lower levels of plasma brain-derived neurotrophic factor were associated with less connectivity between the left amygdala and the medial prefrontal cortex and the inferior frontal gyrus. In addition, within individuals with alcohol use disorder (only), lower levels of brain-derived neurotrophic factor and amygdala-medial prefrontal cortex functional connectivity during anxiety were associated with more binge episodes within the past 60 days and a lower age of alcohol use disorder onset. There were no associations between brain-derived neurotrophic factor levels and focal amygdala task reactivity. Conclusions Together, the results indicate that plasma brain-derived neurotrophic factor levels are related to amygdala circuit functioning in humans, particularly during anxiety, and these individual differences may relate to drinking behaviors.

scholarly journals Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder

2020 ◽  
Vol 44 (7) ◽  
pp. 1488-1496 ◽  
Author(s):  
Verica Milivojevic ◽  
Gustavo A. Angarita ◽  
Gretchen Hermes ◽  
Rajita Sinha ◽  
Helen C. Fox
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Alcohol Craving ◽  
Neuroendocrine Response ◽  
Response To Stress
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