Extrastriatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder and Individuals at High Risk

2022 ◽  
pp. 1-10
Author(s):  
Gianna Spitta ◽  
Tobias Gleich ◽  
Kristin Zacharias ◽  
Oisin Butler ◽  
Ralph Buchert ◽  
...  

<b><i>Introduction:</i></b> Reduced striatal dopamine D2/3 receptor availability in alcohol use disorder (AUD) has been demonstrated in recent clinical studies and meta-analyses. However, only a limited number of studies investigated extrastriatal D2/3 availability in AUD or in at-risk populations. In line with a dimensional understanding of addiction, extrastriatal dopaminergic neuroadaptations have been suggested to be relevant from a pathobiological perspective. <b><i>Methods:</i></b> We investigated D2/3 receptor availability via <sup>18</sup>F-fallypride positron emission tomography applying a region of interest (ROI) approach. We selected ROIs for the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC). Our sample included 19 healthy controls (low risk [LR]), 19 individuals at high risk (HR) to develop addiction, and 20 recently detoxified AUD patients. <b><i>Results:</i></b> We found significantly higher D2/3 receptor availability of HR compared to AUD in the left and right rostral ACC (rACC), as well as in the left ventrolateral PFC (vlPFC). We did not observe a significant difference between AUD and LR. After corrections for multiple comparisons none of the ROIs reached significance throughout the group comparison. The D2/3 receptor availability in the left rACC was inversely correlated with symptom severity assessed with the Alcohol Dependency Scale. <b><i>Discussion:</i></b> To our knowledge, the present work is the first study investigating extrastriatal D2/3 receptor availabilities in individuals at HR and patients with AUD. The observation that D2/3 receptor availabilities are highest in HR might suggest that their pathobiology differs from subjects with AUD. Future studies are necessary to clarify the intraindividual course of this biomarker over different disease stages and its possible role as a risk or protective factor.

2020 ◽  
Author(s):  
Tobias Gleich ◽  
Gianna Spitta ◽  
Oisin Butler ◽  
Kristin Zacharias ◽  
Semiha Aydin ◽  
...  

2018 ◽  
Vol 47 (4) ◽  
pp. 462-468 ◽  
Author(s):  
Kurt Jensen ◽  
Charlotte Nielsen ◽  
Claus Thorn Ekstrøm ◽  
Kirsten K. Roessler

Aim: The aim of this study is to compare the effect of exercise training on physical capacity and alcohol consumption in alcohol use disorder (AUD) patients. Methods: One hundred and five AUD patients were randomly assigned to treatment as usual combined with running and brisk walking for 30–45 min twice a week, either in small supervised groups (GR) or individually (IND), or to a control group with no running (C). Assessments were made after 6 and 12 months of training. Results: Training volume was estimated as 36 min per training bout at an intensity of 78% of HRmax with no differences between GR and IND ( p>.05). A highly significant reduction in training frequency was seen in both training groups after the first month ( p<.0001). Only IND increased VO2max, by 5.7% ( p<.05), while no differences were seen between GR, IND and C. Alcohol intake decreased from 219 to 41 units per 30 days as the average for the entire sample with no significant difference of drinking outcomes between groups ( p<.0001). Conclusions: We saw an effect on drinking habits after running in both groups. However, no additional effect was seen when compared with the control group. A drop in the training frequency during the intervention might have resulted in an insignificant training stimulus.


2018 ◽  
Vol 49 (4) ◽  
pp. 675-684 ◽  
Author(s):  
Rebecca Waller ◽  
Laura Murray ◽  
Daniel S. Shaw ◽  
Erika E. Forbes ◽  
Luke W. Hyde

AbstractBackgroundAlcohol use is commonly initiated during adolescence, with earlier onset known to increase the risk for alcohol use disorder (AUD). Altered function in neural reward circuitry is thought to increase the risk for AUD. To test the hypothesis that adolescent alcohol misuse primes the brain for alcohol-related psychopathology in early adulthood, we examined whether adolescent alcohol consumption rates predicted reward responsivity in the ventral striatum (VS), and in turn, AUD symptoms in adulthood.MethodsA total of 139 low income, racially diverse urban males reported on their alcohol use at ages 11, 12, 15, and 17; completed self-reports of personality, psychiatric interviews, and a functional magnetic resonance imaging (fMRI) scan at age 20; and completed a psychiatric interview at age 22. We measured adolescent alcohol use trajectories using latent growth curve modeling and measured neural responses to monetary reward using a VS region of interest. We tested indirect effects of adolescent alcohol use on AUD symptoms at age 22 via VS reward-related reactivity at age 20.ResultsGreater acceleration in adolescent alcohol use predicted increased VS response during reward anticipation at age 20. VS reactivity to reward anticipation at age 20 predicted AUD symptoms at age 22, over and above concurrent symptoms. Accelerated adolescent alcohol use predicted AUD symptoms in early adulthood via greater VS reactivity to reward anticipation.ConclusionsProspective findings support a pathway through which adolescent alcohol use increases the risk for AUD in early adulthood by impacting reward-related neural functioning. These results highlight increased VS reward-related reactivity as a biomarker for AUD vulnerability.


2020 ◽  
Author(s):  
Vanessa Morris ◽  
Luciano Minuzzi ◽  
Nicholas Bock ◽  
James MacKillop ◽  
Michael Amlung

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&lt;.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.


2019 ◽  
pp. 088626051988386
Author(s):  
Kaitlin E. Bountress ◽  
Daniel Bustamante ◽  
Christina Sheerin ◽  
Danielle M. Dick ◽  
Ananda B. Amstadter ◽  
...  

College is a high-risk time for interpersonal trauma (IPT) exposure (e.g., physical or sexual abuse/assault), a potent form of trauma exposure. College is also a high-risk time for alcohol misuse, as use begins and increases in adolescence and peaks in the early/mid-20s. In addition, although IPT is associated with alcohol misuse, less clear is whether distal (prior to college) or proximal (during college) IPT impacts alcohol use disorder (AUD) symptoms at the beginning of college and/or changes in symptoms during college. Data were collected from a large, longitudinal study of college students, attending a large public university in the southeast, who had reported lifetime IPT as well as lifetime alcohol use. Participants in the current study were 18.5 years old ( SD = 0.46), primarily female (67.2%), and of diverse racial backgrounds (e.g., 53.4% White, 18.5% Black, 12.7% Asian, 15.4% Other). Latent change score analyses were employed to test the impact of IPT prior to college and IPT during college on initial levels of, and changes in, AUD symptoms during college. Those who experienced an IPT prior to college reported more AUD symptoms at the beginning of college and less changes in AUD symptoms during the first year of college. Those who experienced an IPT in the first 2 and last 2 years of college reported greater increases in symptoms in the first 2 and last 2 years of college, respectively. Findings suggest that prevention and intervention efforts for those who experience an IPT prior to or during college may be useful in reducing AUD symptoms during that time period.


2020 ◽  
Vol 10 (2) ◽  
pp. 115 ◽  
Author(s):  
Chella Kamarajan ◽  
Babak A. Ardekani ◽  
Ashwini K. Pandey ◽  
Sivan Kinreich ◽  
Gayathri Pandey ◽  
...  

Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD (n = 30) from healthy controls (CTL, n = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS). The RF model, with a classification accuracy of 76.67%, identified fourteen DMN connections, two neuropsychological variables (memory span and total correct scores of the forward condition of the VST), and all impulsivity factors as significantly important for classifying participants into either the AUD or CTL group. Specifically, the AUD group manifested hyperconnectivity across the bilateral anterior cingulate cortex and the prefrontal cortex as well as between the bilateral posterior cingulate cortex and the left inferior parietal lobule, while showing hypoconnectivity in long-range anterior–posterior and interhemispheric long-range connections. Individuals with AUD also showed poorer memory performance and increased impulsivity compared to CTL individuals. Furthermore, there were significant associations among FC, impulsivity, neuropsychological performance, and AUD status. These results confirm the previous findings that alterations in specific brain networks coupled with poor neuropsychological functioning and heightened impulsivity may characterize individuals with AUD, who can be efficiently identified using classification algorithms such as Random Forest.


2014 ◽  
Vol 38 (7) ◽  
pp. 2015-2023 ◽  
Author(s):  
Vivia V. McCutcheon ◽  
John R. Kramer ◽  
Howard J. Edenberg ◽  
John I. Nurnberger ◽  
Samuel Kuperman ◽  
...  

2020 ◽  
Author(s):  
Adeline Rose Dozois ◽  
Paulina Nkondora ◽  
Erin E Noste ◽  
Juma Mfinanga ◽  
Hendry R Sawe ◽  
...  

Abstract Background Road traffic accidents (RTAs) have emerged as an important public health problem in low and middle-income countries, where 90% of RTA deaths occur. The World Health Organization has suggested strategies to address excess mortality from RTAs including efforts to combat driving while intoxicated. The association between substance use and RTAs is well known in high-income countries, but data is more limited in low-resource settings including Tanzania. The objective of this study is to examine the prevalence of drug use, alcohol use, and substance use disorders in Tanzanian RTA drivers. Methods This prospective observational study was conducted in the Emergency Department of Muhimbili National Hospital, a national referral hospital in Dar es Salaam, Tanzania. Research assistants available 24 hours per day enrolled adult drivers who presented within 24 hours of an RTA. In eligible patients, research assistants collected a saliva test of blood alcohol content (BAC) and a urine drug screen (UDS), and administered a validated substance abuse screening tool, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Patients were excluded from individual analyses if they could not produce a saliva or urine test or answer questions. Primary outcomes were rates of positive BAC, UDS and self-reported high-risk alcohol and drug use patterns. Descriptive statistics were calculated using Excel. Results We screened 5264 trauma patients and enrolled 538, in whom 191 had a BAC, 362 had a UDS, and 417 had a complete ASSIST. Fifteen of 191 patients (7.8%) had a positive BAC, and 68/362 (18.7%) patients had a UDS that was positive for at least one drug. Based on the ASSIST, 104/417 (24.5%) of patients were at moderate or high risk for alcohol use disorder. Few were at risk for disordered use of other non-tobacco substances. Conclusion In our population of drivers presenting within 24 hours of an RTA, positive BAC and UDS tests were rare. A substantial portion of the population was at moderate to high risk for an alcohol use disorder. Ideal screening for substance use in trauma populations may involve a verbal screening tool, particularly when the time between injury and hospital arrival is delayed.


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