Advances in drug and alcohol research最新文献

Background: Adolescents with externalizing (EXT) disorders, such as attention-deficit/hyperactivity disorder and conduct disorder-characterized by impulsivity and rule-breaking, are at elevated risk for substance use disorders (SUDs), partly due to deficits in risky decision-making. Sex differences in this association are understudied. Neuroimaging research shows females and males with EXT disorders exhibit different brain activation patterns during risky decisions. This study will explore how these sex differences relate to the development of problematic substance use in youth with EXT disorders.

Method: A total of 115 (78 males, 37 females) drug-naive adolescents with EXT psychopathology performed the Balloon Analogue Risk Task (BART) during magnetic resonance imaging to assess risky decision-making brain activation. Then, participants and their guardians completed questionnaires at 6-month intervals to assess problematic substance use. Statistical analyses evaluated sex differences in brain activation-both parametrically modulated and unmodulated-within a priori-selected regions associated with risky decision-making and problematic substance use, using Cox proportional hazards models.

Results: Higher modulated brain activation (as explosion probability increased) during the choice phase contrast, Choose Inflate-Choose Win, was associated with a lower hazard of problematic substance use in the right nucleus accumbens (Hazard Ratio (HR) = 0.68, 95% CI [0.49, 0.94], p = 0.01). This association was significant for females, but not for males, with the hazard ratios being significantly different between sexes. In the right nucleus accumbens, higher unmodulated choice phase activation in males was associated with lower hazard of problematic substance use (HR = 0.60, 95% CI [0.37, 0.97], p = 0.03); and in the right subgenual anterior cingulate cortex, higher unmodulated activation in this same contrast in females was associated with a lower hazard of problematic substance use [HR = 0.49, 95% CI (0.24, 0.97), p = 0.03].

Conclusion: This study offers insight into sex differences in risky decision-making neural mechanisms and SUD risk among youth with EXT disorders. Our findings suggest typical risk signaling in the reward-processing network (nucleus accumbens and subgenual anterior cingulate cortex) may protect against substance use, particularly in females with EXT disorders. These findings emphasize the need for further sex-specific research and interventions for youth with EXT disorders.

Background: Alcohol use disorder (AUD) marked by heavy chronic or binge alcohol consumption, causes cerebellar and white matter (WM) atrophy with cognitive-motor impairments. Major pathological features of alcohol-related brain damage (ARBD) include alterations in WM integrity with myelin loss, and cerebellar degeneration with neuronal loss.

Purpose: This study characterizes molecular and biochemical oligodendrocyte-related pathology in cerebellar tissue from donors with AUD to better understand the mechanisms of ARBD in humans.

Methods: Cores of cerebellar vermis, including cortex and underlying WM from adult human postmortem AUD and control brains, were processed for RNA and protein analyses using duplex and multiplex panels.

Results: AUD cerebellar WM had significant alterations in immature and mature oligodendrocyte protein and mRNA expression, and reduced expression of hepatocyte growth factor, Akt and GSK-3β signaling molecules, and Notch pathway activation. Moreover, the only significant AUD-related alteration in cerebellar cytokine/chemokine expression was reduced IL-16 immunoreactivity.

Conclusion: Human AUD WM degeneration is associated with oligodendrocyte dysfunction, which mechanistically could be mediated by impairments in insulin/IGF signaling through Akt/GSK-3β or Notch pathway activation. Future studies should focus on the non-invasive detection and monitoring of AUD-related oligodendrocyte pathology through the analysis of cell-type-specific exosomes isolated from peripheral blood.

During pregnancy, the fetal brain undergoes rapid development and is highly sensitive to environmental influences. Understanding the intricate processes that underlie fetal brain development will be critical for advancing maternal-fetal health and mitigating the risks associated with developmental brain disorders. Nonhuman primate (NHP) animal models provide a unique and highly translational platform for studying brain development during pregnancy due to the close anatomical, physiological, and behavioral resemblance of these animals to humans. Our review explores the use of NHP models in elucidating key milestones of prenatal brain maturation and the mechanisms that govern typical and atypical development. We further examine the impact of environmental insults on fetal brain development, including air pollution, infection, ionizing radiation, and exposure to toxicants, and highlight the ways in which these factors can disrupt brain development and neural circuitry, leading to long-term cognitive and behavioral deficits. Recent studies demonstrate that the baboon (Papio hamadryas) animal model provides a fruitful yet underused translational model for research related to environmental adverse effects on pregnancy. Lastly, we review the effects of drugs of abuse on the developing fetal brain, highlighting the underlying biological mechanisms identified through clinical and laboratory studies. A combined approach offers a comprehensive understanding of the vulnerabilities of the developing nervous system, informing new strategies for the treatment and prevention of neurodevelopmental disorders.

Alcohol withdrawal is characterized by various symptoms that include pain and negative affect in the absence of the drug. The neural underpinnings of these behaviors are not entirely understood, but orexin has emerged as a candidate target for the treatment of substance use disorders. Here, we explored changes in orexin system-related gene expression in brain regions important for mediating reward and stress, including the ventral tegmental area (VTA) and extended amygdala (including the central amygdala, nucleus accumbens shell, and bed nucleus of the stria terminalis), in adolescent and adult female Wistar rats following chronic alcohol exposure. We observed higher numbers of Hcrtr1- (orexin receptor 1)-expressing neurons in the VTA of adolescent and adult female rats during withdrawal from chronic alcohol exposure. The number of Hcrt1+ VTA neurons was negatively correlated with thermal sensitivity in adolescent female rats and anxiety-like behavior in adult female rats. These data suggest that chronic alcohol effects on orexin receptor expression in the VTA are related to specific behaviors that manifest during withdrawal, highlighting potential avenues for targeting alcohol withdrawal-associated behaviors across development.

At-risk alcohol and illicit drug use are risk factors for disease and in-hospital complications. This study investigated whether clinicians document substance use in the electronic records of acutely hospitalized internal medicine patients. Alcohol and illicit drug positive patients were identified using prospectively gathered substance use data from a study sample comprising 2,872 patients included from November 2016 to December 2017 at an internal medicine hospital in Oslo, Norway. These data were unknown to hospital staff. Whether physicians recorded quantitative substance use assessments and interventions was examined in patients with study-verified alcohol use in excess of low-risk guidelines (Alcohol Use Disorder Identification Test-4 scores [AUDIT-4] of ≥5 for women and ≥7 for men) and/or illicit drug use (one or more illicit drug detected by liquid chromatography-mass spectrometry [LC-MS] analysis). Among 548 study-verified alcohol-positive patients, physicians documented quantity and frequency (QF) of use in 43.2% (n = 237) and interventions in 22.0% (n = 121). Alcohol interventions were associated with harmful drinking (AUDIT-4 ≥9 points; adjusted odds ratio [AOR] = 4.87; 95% CI: 2.54-9.31; p < 0.001) and QF assessments (AOR = 3.66; 95% CI: 1.13-11.84; p = 0.02). Among 157 illicit-positive patients, drug use was described quantitatively in 34.4% (n = 54) and interventions in 26.0% (n = 40). The rate of quantitative alcohol and illicit drug use assessment by hospital physicians is poor, with a correspondingly low intervention rate. Important opportunities for attenuating or intervening in at-risk alcohol and illicit drug use are missed.

As part of a broader qualitative study aimed at understanding the experiences and opinions of adolescents and young adults (AYA) who do not drink alcohol in Switzerland, participants were questioned about their perceptions of the term "abstinence" in the context of alcohol non-consumption. Twelve focus groups were conducted with 63 participants (36 females, 27 males), aged between 14 years and 20 years. Participants were grouped by gender, age (based on Swiss alcohol laws), and drinking status (non-drinker or drinker). The discussions were recorded and transcribed, and thematic content analysis was used to identify and categorize key themes. The terms "abstinence," "abstainer," and "abstention" were generally considered unsuitable when describing young people who do not consume alcohol regardless of the drinking status of the participants. The connotation carried by the terms was mostly perceived as religious, sexual, negative and stigmatizing. "Abstinence" was considered more appropriate for adults who have stopped drinking due to alcohol-related issues. When referring to youths, terms such as "non-drinking," "non-drinkers" or "alcohol non-consumption" were preferred, especially to better integrate non-drinking youths and positively highlight their choices in preventive and educational initiatives.

Aims: The objective of this study is to illustrate the application of a machine learning algorithm, K Nearest Neighbor (k-NN) to impute missing alcohol data in a prospective study among pregnant women.

Methods: We used data from the Safe Passage study (n = 11,083). Daily alcohol consumption for the last reported drinking day and 30 days prior was recorded using the Timeline Follow back method, which generated a variable amount of missing data per participants. Of the 3.2 million person-days of observation, data were missing for 0.36 million (11.4%). Using the k-NN imputed values were weighted for the distances and matched for the day of the week. Since participants with no missing days were not comparable to those with missing data, segments of non-missing data from all participants were included as a reference. Validation was done after randomly deleting data for 5-15 consecutive days from the first trimester.

Results: We found that data from 5 nearest neighbors (i.e., K = 5) and segments of 55 days provided imputed values with least imputation error. After deleting data segments from the first trimester data set with no missing days, there was no difference between actual and predicted values for 64% of deleted segments. For 31% of the segments, imputed data were within +/-1 drink/day of the actual. Imputation accuracy varied by study site because of the differences in the magnitude of drinking and proportion of missing data.

Conclusion: k-NN can be used to impute missing data from longitudinal studies of alcohol during pregnancy with high accuracy.