Alcoholism, clinical and experimental research最新文献

Background: The period of college represents a particularly risky developmental stage with regard to alcohol use, as college students engage in more risky drinking behaviors than their noncollege peers, and such problematic alcohol use is associated with far-reaching negative consequences. Existing findings from genome-wide association studies (GWAS) indicate that alcohol consumption has a complex polygenic etiology. Currently, there is a lack of studies examining genetic risk for alcohol consumption using polygenic risk scores (PRS) in college samples. In this study, we examined whether alcohol-specific and risky behavior-related PRS were longitudinally associated with alcohol consumption among college students and whether this effect might be partially mediated by impulsivity domains.

Methods: The sample included n = 2,385 European ancestry (EA) and n = 1,153 African ancestry (AA) college students assessed over the course of 4 years. To indicate genetic risk, 2 PRS were created based on recent large-scale GWAS: alcohol consumption (Liu et al., 2019) -drinks per week (DPW)-PRS and risky behaviors (Linnér et al., 2019) -RISK-PRS. The main outcome was alcohol consumption, measured across 4 waves of follow-up data. The UPPS-P impulsivity subscales were examined as mediators of the genetic effect on alcohol consumption.

Results: The results from structural equation modeling showed that among EA students, both DPW-PRS and RISK-PRS had significant positive effects on alcohol consumption above and beyond UPPS dimensions and control variables. RISK-PRS explained larger portion of variance in alcohol consumption than DPW-PRS. RISK-PRS showed a significant indirect effect on alcohol consumption through sensation seeking and lack of perseverance; no significant indirect effect of DPW-PRS was found. No significant association of either PRS or alcohol consumption was found for AA participants.

Conclusions: The current results found that PRS related to more broadly defined risky behaviors predicted alcohol consumption across college years and that this association was partially mediated via dimensions of impulsivity.

Alcohol use disorder (AUD) is a chronic relapsing condition that represents a significant public health concern. Pharmacological treatment development for AUD is a top research priority, and many studies are being conducted to evaluate potential AUD treatments. Understanding the brain circuitry impacted by addiction is crucial for the development of efficacious pharmacological interventions. These neuroadaptations can be probed noninvasively using functional magnetic resonance neuroimaging (fMRI). fMRI may be an effective tool to identify biomarkers for AUD pharmacotherapies, evaluating changes associated with pharmacological treatment. Thus, the present qualitative review of the literature focuses on the role of fMRI as a tool for medication development for AUD. The aim of this review was to assemble research across a range of fMRI paradigms to study the effectiveness of pharmacological treatments of adult AUD. First, we present a qualitative review of fMRI AUD pharmacotherapy studies, differentiating studies based on their dosing regimen. Second, we provide recommendations for the field to improve the use of fMRI as a biomarker for AUD pharmacotherapy.

Background: Acute alcohol produces effects on cerebral metabolism and blood flow. Alcohol is converted to acetate, which serves as a source of energy for the brain and is an agonist at G protein-coupled receptors distributed in different cell types in the body including neurons. Acetate has been hypothesized to play a role in the cerebral blood flow (CBF) response after alcohol ingestion. We tested whether administration of acetate would alter CBF in a pattern similar to or different from that of alcohol ingestion in healthy individuals.

Methods: Twenty-four healthy participants were assigned by convenience to receive either 0.6 g/kg alcohol orally (n = 12) or acetate intravenously (n = 12). For each participant, CBF maps were acquired using an arterial spin labeling sequence on a 3T magnetic resonance scanner after placebo and after drug administration. Whole-brain CBF maps were compared between placebo and drug using a paired t-test, and set at a threshold of p < 0.05 corrected for multiple comparisons (k ≥ 142 voxels, ≥3.78 cm³ ), voxel-level p < 0.005. Intoxication was measured after placebo and drug administration with a Subjective High Assessment Scale (SHAS-7).

Results: Compared to placebo, alcohol and acetate were associated with increased CBF in the medial thalamus. Alcohol, but not acetate, was associated with increased CBF in the right orbitofrontal, medial prefrontal and cingulate cortex, and hippocampus. Plasma acetate levels increased following administration of alcohol and acetate and did not differ between the 2 arms. Alcohol, but not acetate, was associated with an increase in SHAS-7 scores (p < 0.001).

Conclusions: Increased thalamic CBF associated with either alcohol or acetate administration suggests that the thalamic CBF response after alcohol could be mediated by acetate. Compared to other brain regions, thalamus may differ in its ability to metabolize acetate or expression of receptors responsive to acetate. Increased prefrontal and limbic CBF associated with alcohol may be linked to alcohol's behavioral effects.