Imaging a putative marker of brain cortisol regulation in alcohol use disorder.

Background: Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans. We used positron emission tomography (PET) brain imaging with the radiotracer [18F]AS2471907 to measure 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), a cortisol-regenerating enzyme, in people with AUD compared to healthy controls. Methods: We imaged 9 individuals with moderate to severe AUD (5 men, 4 women; mean age = 38 years) and 12 healthy controls (8 men, 4 women; mean age = 29 years). Participants received 93.5 ± 15.6 MBq of the 11ß-HSD1 inhibitor radiotracer [18F]AS2471907 as a bolus injection and were imaged for 150-180 min on the High-Resolution Research Tomograph. 11ß-HSD1 availability was quantified by [18F]AS2471907 volume of distribution (VT; mL/cm3). A priori regions of interest included amygdala, anterior cingulate cortex (ACC), hippocampus, ventromedial PFC (vmPFC) and caudate. Results: Individuals with AUD consumed 52.4 drinks/week with 5.8 drinking days/week. Healthy controls consumed 2.8 drinks/week with 1.3 drinking days/week. Preliminary findings suggest that [18F]AS2471907 VT was higher in amygdala, ACC, hippocampus, vmPFC, and caudate of those with AUD compared to healthy controls (p < 0.05). In AUD, vmPFC [18F]AS2471907 VT was associated with drinks per week (r = 0.81, p = 0.01) and quantity per drinking episode (r = 0.75, p = 0.02). Conclusions: This is the first in vivo examination of 11ß-HSD1 availability in individuals with AUD. Our data suggest higher brain availability of the cortisol-regenerating enzyme 11ß-HSD1 in people with AUD (vs. controls), and that higher vmPFC 11ß-HSD1 availability is related to greater alcohol consumption. Thus, in addition to the literature suggesting that people with AUD have elevated peripheral cortisol, our findings suggest there may also be heightened central HPA activity. These findings set the foundation for future hypotheses on mechanisms related to HPA axis function in this population.

The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption.

Sex steroid hormone levels associated with dopamine D2/3 receptor availability in people who smoke cigarettes.

Introduction: Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls. Methods: Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [11C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D2R availability (BPND) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone. Results: Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BPND. Discussion/conclusion: This study demonstrated that lower estradiol levels are associated with lower dlPFC D2R availability in women which may underlie difficulty resisting smoking.

Liquor consumption is associated with other medical conditions in females who consume alcohol.

Background: Our group previously identified that females with AUD and females engaging in heavy or extreme binge drinking were more likely to report cancers and other medical conditions compared to their male counterparts. This analysis aimed to extend our previous findings to examine relationships between sex and consumption of alcohol by type on past year medical condition diagnoses. Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol type (liquor, wine, beer, coolers) on past year self-reported doctor-confirmed medical conditions, controlling for frequency of alcohol consumption. Results: A significant interaction demonstrated that females who consumed liquor were more likely to have other medical conditions (OR=1.95) compared to males who consumed liquor. Females who consumed wine in the past year were less likely to have cardiovascular conditions (OR=0.81) compared to males who consumed wine. Those who consumed liquor had increased odds of pain, respiratory, and other conditions (OR=1.11 - 1.21). Females were 1.5 times more likely to have cancers or pain, respiratory, and other medical conditions compared to males (OR=1.36 - 1.81). Conclusions: Results identify that consumption of higher alcohol content drinks (i.e., liquor) is associated with past year self-reported doctor- or health-professional confirmed medical conditions in females compared to males consuming the same high alcohol content beverage. Not only should AUD status and risky drinking be considered in the clinical care of individuals with poorer health but also alcohol type, especially higher alcohol content beverages.

Lower Dopamine D2/3 Receptor Availability is Associated With Worse Verbal Learning and Memory in People Who Smoke Cigarettes.

INTRODUCTION: Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control. We recently showed that dlPFC dopamine D2/3-type receptor (D2R) availability was significantly lower in people who smoke than in healthy-controls and that dlPFC amphetamine-induced dopamine release was lower in females who smoke relative to males who smoke and female healthy-controls. However, we did not examine whether the smoking-related dopamine deficits were related to cognitive deficits. AIMS AND METHODS: The goal of this study was to relate dopamine metrics to cognitive performance in people who smoke and healthy-controls. In total 24 (12 female) people who smoke cigarettes and 25 sex- and age-matched healthy-controls participated in two same-day [11C]FLB457 positron emission tomography (PET) scans before and after amphetamine administration. Two outcome measures were calculated-D2R availability (non-displaceable binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND). Cognition (verbal learning and memory) was assessed with a computerized test from the CogState battery (International Shopping List). RESULTS: People who smoke had significantly worse immediate (p = .04) and delayed (p = .03) recall than healthy-controls. Multiple linear regression revealed that for people who smoke only, lower D2R availability was associated with worse immediate (p = .04) and delayed (p < .001) recall. %ΔBPND was not significantly related to task performance. CONCLUSION: This study demonstrated that lower dlPFC D2R availability in people who smoke is associated with disruptions in cognitive function that may underlie difficulty with resisting smoking. IMPLICATIONS: This is the first study to directly relate dopamine metrics in the prefrontal cortex to cognitive function in people who smoke cigarettes compared to healthy-controls. The current work included a well-characterized subject sample with regards to demographic and smoking variables, as well as a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature by relating dopamine metrics to cognition in people who smoke, providing a better understanding of brain-behavior relationships.

Adverse Childhood Experiences and Pathways to Violent Behavior for Women and Men.

Childhood maltreatment is associated with risk for committing future violence, but the relationship between subgroups and biological sex is unknown. The relationship between adverse childhood experiences (ACEs), violence, and sex was examined using a nationally representative sample. Results from a latent class analysis suggested a four-class model (low adversity; moderate maltreatment with high household dysfunction; severe maltreatment with moderate household dysfunction; severe multi-type adversities). When compared to low adversity, all typology groups were at significantly higher risk to engage in violence (odds ratio > 2.10, ps < .013). The data supported a linear trajectory, meaning increased childhood trauma was associated with increased risk for violence. Although men endorsed more violent behavior, the relationship between ACEs and violence was significantly stronger among women. Prior findings identify that women are more negatively impacted by ACEs and the current findings newly identify that this extends to violent crime.

A novel human laboratory alcohol self-administration paradigm for medication screening: Modeling the ability to resist drinking and heavy drinking.

Background: Human laboratory analogues of drinking behavior provide an efficient, cost-effective mechanistic evaluation of a medication signal on drinking. We developed a novel alcohol self-administration paradigm which models the ability to resist drinking and heavy drinking. Methods: We compared a de-escalating schedule of monetary reinforcement (n=16, 50% female) to no schedule (n=16, 50% female) on the ability to resist drinking (i.e., latency to start drinking) and subsequent ad-libitum alcohol consumption of preferred alcoholic beverage in participants with alcohol use disorder (AUD). Participants completed two laboratory sessions designed to model the ability to resist drinking using stress (versus neutral imagery, within-subject factor) as a prime for drinking. Results: Participants consumed more alcohol with no schedule (74.2%) versus with the de-escalating reinforcement schedule (40.3%,). The de-escalating schedule reduced alcohol consumption by 49%. Eighty-one percent of participants drank heavily with no schedule and this was reduced with the schedule. Use of the de-escalating schedule also increased the latency to pour and sip the first drink. Participants poured and sipped alcohol faster following stress imagery (vs. neutral), had greater craving, and consumed more alcohol in the first 30 minutes. Conclusions: Our novel alcohol self-administration model generated heavy drinking. Over 80% of participants without reinforcement consumed more than 2/3 of their preferred alcoholic beverage designed to increase blood alcohol levels to 0.12 mg% within a 2-hour window. Our model was sensitive to stress, and the de-escalating schedule highlighted stress effects on drinking. Thus, this model is ideal for a cross-over design to test medications for AUD.

Licit and illicit drug use across trimesters in pregnant women endorsing past-year substance use: Results from National Survey on Drug Use and Health (2009-2019).

PURPOSE: Given the health consequences, perinatal substance use is a significant public health concern, especially as substance use rates increase among women; ongoing data regarding the rates of substance use across trimesters of pregnancy is needed. METHODS: The present study utilized cross-sectional population-based data from the National Survey of Drug Use and Health (NSDUH) between 2009 and 2019. We aimed to explore both licit and illicit substance use assessed within each trimester among women endorsing past-year substance use. The NSDUH sample included 8,530 pregnant women. RESULTS: Perinatal substance use was less prevalent among women in later trimesters; however, past-month substance use was observed for all substances across trimesters. The prevalence of past-month licit substance use among pregnant women ranged from 5.77 to 22.50% and past-month illicit substance use ranged from 4.67 to 14.81%. In the second trimester, lower odds of past-month substance use were observed across tobacco, alcohol, and marijuana (odds ratios [ORs] ranging from 0.29 to 0.47), when compared to the first trimester. A similar lower rate of past-month substance use was observed in the third trimester compared to the first trimester, across tobacco, alcohol, and marijuana use, as well as cocaine, prescription pain medication, and tranquilizer use (ORs ranging from 0.02 to 0.42). The likelihood of polysubstance use was lower among women in the second and third trimesters compared to the first trimester (ORs ranging from 0.09 to 0.46). CONCLUSION: Findings indicate that a minority of women continue to use substances across all trimesters. This is especially true among women using licit substances and marijuana. These results highlight the need for improved interventions and improved access to treatment for these women.

Sex Differences across Retrospective Transitions in Posttraumatic Stress and Substance Use Disorders.

Objectives: Concurrent substance use disorder (SUD) and posttraumatic stress disorder (PTSD) occur at high rates and are typically associated with poor treatment outcomes in both sexes. However, women have a propensity to cope with increased negative affect via substance use in comparison to men; thus, it is important to elucidate the sex-specific bidirectional relationships between SUD and PTSD to improve our understanding of concurrent SUD/PTSD in men and women. Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-Wave 3; n = 36,309), the present study evaluated the impact of sex on the relationship between past-year SUDs (new, remitted, ongoing), including alcohol and drug use, and retrospective transitions in new vs. absent and ongoing vs. remitted diagnoses of PTSD. Additionally, the impact of sex was explored in models examining past year PTSD (new, remitted, ongoing) and retrospective transitions in new vs. absent and ongoing vs. remitted diagnosis of SUDs. Diagnostic transitions were based on retrospective reporting. Results: Results indicated that new, remitted, and ongoing SUDs increase the likelihood of new PTSD diagnoses (OR range = 2.53-8.11; p < 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD (OR = 2.10, p < 0.01). When examining the relationship reciprocally, new, remitted, and ongoing PTSD increased the likelihood of new SUDs (OR range = 2.50-8.22; p < 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD (OR = 1.40, 1.70, respectively; p < 0.05). Sex-specific analyses revealed that the relationship between PTSD and SUDs varies between sexes, particularly among women. For instance, women with new PTSD had higher odds of SUDs, and women with ongoing PTSD were almost 2.5 times more likely to have an ongoing DUD. Women with a new PTSD diagnosis were more likely to be diagnosed with a new SUD (OR = 3.27) and an ongoing DUD (OR = 3.08). Conclusions: Results indicate a bidirectional relationship between PTSD and SUD that is in many instances larger in women. Thus, illustrating potential sex-specific differences in underlying mechanisms implicated in SUD/PTSD, warranting additional research.

Prospective Associations of Pain Intensity and Substance Use in the United States Population: A Cross-Lagged Panel Analysis.

OBJECTIVE: Pain is associated with increased risk for harmful substance use. Substance use also may increase levels of pain, suggesting that these two factors may reciprocally increase risk. The current study examined the reciprocal association between pain and substance use outcomes (i.e., alcohol, cannabis, and painkillers/sedatives/tranquilizers [PSTs]) longitudinally in a nationally representative cohort of non-incarcerated U.S. citizens. METHOD: Adult (≥18 years old) survey data from Waves 2-4 of the Population Assessment of Tobacco and Health (PATH) study were used. The PATH is a nationally representative multiwave cohort survey (Wave 2: October 2014-October 2015, Wave 3: October 2015-October 2016, Wave 4: December 2016-January 2018). Cross-lagged panel models were used to estimate the reciprocal effects of pain intensity and substance use on subsequent changes in both variables. Substance use outcomes were substance use problems and greater-than-weekly use for cannabis and PSTs, total past-month drinks, and alcohol use exceeding moderate drinking guidelines. All models controlled for autoregressive effects and demographic covariates. RESULTS: Pain intensity showed a positive prospective association with all substance use outcomes. All cannabis and PST use were positively associated with subsequent pain intensity. Alcohol use problems also predicted higher levels of pain intensity. Neither total past-month drinks nor exceeding moderate drinking guidelines predicted subsequent pain intensity. CONCLUSIONS: Pain and substance use show a reciprocal association and may act in a positive feedback loop to worsen both conditions over time in people with a history of use.

Sex and alcohol use disorder predict the presence of cancer, respiratory, and other medical conditions: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III.

BACKGROUND: Women experience greater health consequences of alcohol compared to their male counterparts. In recent years, rates of drinking and heavy alcohol use have increased in women while remaining relatively steady in men. Thus, our aim was to newly examine associations between sex, AUD, and the presence of medical conditions in a large nationally representative, cross-sectional dataset. METHODS: Using data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309), we evaluated relationships among sex and DSM-5 AUD, and their association with past year clinician-confirmed medical conditions. RESULTS: Women were 1.5 to 2 times more likely to be diagnosed with a past year cancer, pain, respiratory, or other significant medical condition compared to men (odds ratio [OR] = 1.331-2.027). Individuals with an ongoing DSM-5 AUD were nearly 1.5 to 2 times more likely to report a confirmed past year liver, cardiovascular, cancer, or other significant medical condition compared to those without an AUD (OR = 1.437-2.073). Interactive effects demonstrated that women with an ongoing AUD were 2 to 3 times more likely to report a past year doctor- or health professional-confirmed medical condition compared to men; specifically, respiratory conditions and cancers (OR = 1.767-2.713). CONCLUSIONS: Results identify that AUD is a critical factor associated with disease that spans organ systems. Associations between AUD and respiratory conditions or cancers are particularly robust in women. Effective interventions for a broad spectrum of medical conditions should consider the role of problematic alcohol use, especially given that rates of drinking in women are increasing.

Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders.

Stress and trauma exposure disturbs stress regulation systems and thus increases the vulnerability for stress-related disorders which are characterized by negative affect, including major depressive disorder, anxiety disorders and posttraumatic stress disorder. Similarly, stress and trauma exposure results in increased vulnerability to problematic alcohol use and alcohol use disorder, especially among women, who are more likely to drink to cope with negative affect than their male counterparts. Given these associations, the relationship between stress-related disorders and alcohol use is generally stronger among women leading to complex comorbidities across these disorders and alcohol misuse. This review highlights the therapeutic potential for progestogen- and androgen-derived neurosteroids, which affect both stress- and alcohol-related disorders, to target the overlapping symptoms related to negative affect. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'

Gender and past year serious psychological distress are associated with past year AUD: Time-varying results from the National Survey on Drug Use and Health (NSDUH; 2008-2017).

BACKGROUND: Rates of alcohol use disorder (AUD) have increased in women in the last decade. Women may be more likely to engage in alcohol use to regulate stress and negative affect compared to men. Findings from our group found that life event stress was more strongly associated with new AUD in women vs. men. Our aim was to extend these findings to psychological distress, a potentially related construct to stress, using a second nationally representative dataset. METHODS: Using data from the National Survey on Drug Use and Health (NSDUH; 2008-2017, total n = 562,072), we examined time-varying associations between gender and past year serious psychological distress (SPD; Kessler-6 distress scale: scores > 13 yes, <13 no) with past year vs. absent DSM-IV AUD. RESULTS: A significant (p < 0.0001) gender by SPD interaction for past year vs. absent AUD demonstrated that past year SPD was associated with increased odds of past year AUD in men (OR = 3.33, 95% CI = 3.15, 3.52) and even greater odds of past year AUD in women (OR = 4.39, 95% CI = 4.14, 4.66). The gender by SPD by time interaction was not significant (p = 0.06). CONCLUSIONS: Results highlight that while men with past year SPD were 3 times more likely to have a past year AUD, women with past year SPD were nearly 4.5 times more likely to have a past year AUD. Psychological distress is clearly an important factor in AUD in both men and women, but results suggest that other factors may be driving the increase in rates of AUD in women.

Risk drinking levels and sex are associated with cancer and liver, respiratory, and other medical conditions.

Background: Heavy alcohol use is associated with increased risk of alcohol-related health consequences. Alcohol consumption has increased in females in the last fifteen years and females are more likely to experience exacerbated health risks due to drinking. Our group identified that females with AUD were more likely to report respiratory conditions or cancers compared to their male counterparts. This analysis sought to further examine relationships between sex and alcohol use on medical conditions by using the new 2020 U.S. Dietary Guidelines risk drinking levels. Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol risk drinking levels (abstainer, binge, heavy, extreme binge vs. moderate drinking) on past year self-reported doctor-confirmed medical conditions). Results: Females were 1.5 to 2 times more likely to have pain, respiratory, or other medical conditions in the past year (odds ratio [OR]=1.46-2.11) vs. males. Significant interactions demonstrated that heavy drinking females or extreme binge drinking females were 2 to 3 times more likely to have cancers or other conditions (OR=1.95-2.69) vs. males at the same risk drinking level. Female abstainers were more likely than male abstainers to have other medical conditions (OR=1.77). Conclusions: Consistent with our previous findings, results identify that higher risk drinking levels are associated with the presence of past year self-reported doctor-confirmed medical conditions spanning organ systems, particularly in females. Treatment for high-risk drinking should be considered in the clinical care of individuals with significant medical conditions.

Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years.

Over the last 10 years, rates of alcohol use disorder (AUD) have increased in women by 84% relative to a 35% increase in men. Rates of alcohol use and high-risk drinking have also increased in women by 16% and 58% relative to a 7% and 16% increase in men, respectively, over the last decade. This robust increase in drinking among women highlights the critical need to identify the underlying neural mechanisms that may contribute to problematic alcohol consumption across sex/gender (SG), especially given that many neuroimaging studies are underpowered to detect main or interactive effects of SG on imaging outcomes. This narrative review aims to explore the recent neuroimaging literature on SG differences in brain function and structure as it pertains to alcohol across positron emission tomography, magnetic resonance imaging, and functional magnetic resonance imaging modalities in humans. Additional work using magnetic resonance spectroscopy, diffusion tensor imaging, and event-related potentials to examine SG differences in AUD will be covered. Overall, current research on the neuroimaging of AUD, alcohol consumption, or risk of AUD is limited, and findings are mixed regarding the effect of SG on neurochemical, structural, and functional mechanisms associated with AUD. We address SG disparities in the neuroimaging of AUD and propose a call to action to include women in brain imaging research. Future studies are crucial to our understanding of the neurobiological underpinnings of AUD across neural systems and the vulnerability for AUD among women and men.

A Critical Review of Alcohol Administration Guidelines in Laboratory Medication Screening Research: Is It Time to Include Treatment Seekers?

Human laboratory studies play an important role in alcohol use disorder (AUD) medication development. Medications that are found to be safe and effective during human laboratory screening will then move to more expensive clinical trials in patient populations. Given the gatekeeping role of human laboratory studies in the medication development pipeline, it is critical that these studies accurately forecast how pharmacotherapies will perform under true-to-life clinical conditions. On the other hand, the design of these studies also must adhere to ethical guidelines: certain aspects of clinical reality cannot be incorporated into screening studies because doing so might place the participant at risk for harm or breach other ethical guidelines. Conventions exist that guide the resolution of these conflicting ideals. This article considers the practice of recruiting non-treatment-seeking heavy drinkers to participate in laboratory screening studies. By convention, volunteers are excluded from laboratory screening studies that involve alcohol administration if they are deemed "treatment seeking," meaning that they recently stopped drinking or are motivated to do so. Although this common practice may reduce risk to participants, findings may not accurately predict medication effects on treatment seekers. Indeed, there is empirical evidence that treatment seekers differ from nontreatment seekers in their responses to medications (Neuropsychopharmacology 2017a; 42: 1776; Am J Drug Alcohol Abuse 2017b; 43: 703; J Psychiatr Res 2006; 40: 383). Here, we argue for the importance of recruiting treatment seekers for this research due to their qualitative difference from nontreatment seekers. We argue that these individuals should be the default population in human laboratory medication screening studies. We conclude by discussing 2 case examples of medication experiments led by our research groups that involved administering medications to treatment seekers.

The Prevalence of Substance Use Disorders among Community-based Adults with Legal Problems in the U.S.

BACKGROUND: Current national prevalence estimates of DSM-5 diagnosed substance use disorders (SUDs) among adults with justice system involvement are lacking. METHODS: This study drew from NESARC-III data (n = 36,309; 2012-2013), a nationally representative U.S. sample, to examine current and lifetime alcohol use disorder (AUD) and drug use disorder (DUD) diagnoses among adults reporting current or prior drug-related, alcohol-related, and general legal problems. RESULTS: Adults reporting current alcohol-related legal problems were 22 times more likely to have a current AUD diagnosis (AOR = 22.0, 95% CI = 12.1; 40.1) and 15 times more likely to have had a lifetime AUD diagnosis (AOR = 15.2, 95% CI = 7.5; 30.9) than adults without alcohol-related legal problems. Adults with lifetime drug-related legal problems were 3-5 times more likely to have a current (AOR = 2.6, 95% CI = 2.1; 3.2) and lifetime (AOR = 5.1, 95% CI = 4.3; 6.1) DUD diagnosis, with stimulant use disorder being the most prevalent (AOR = 5.4, 95% CI = 4.5; 6.5). Adults with general legal problems were around 3 times more likely to have a current AUD (AOR = 3.2, 95% CI = 2.6; 4.0) or DUD (AOR = 3.5, 95% CI = 2.8; 4.4). Women with any type of legal problem were more likely to have SUD diagnoses than men. CONCLUSIONS: SUD diagnoses are prevalent among adults reporting legal problems, particularly those involving alcohol. There is a continued need for community-based addiction prevention and intervention efforts, especially for women with justice system involvement.

A prospective study of the association between rate of nicotine metabolism and alcohol use in tobacco users in the United States.

BACKGROUND: Rate of nicotine metabolism has been identified as a biochemical risk factor for nicotine use and dependence; however, its role in alcohol consumption and related outcomes is not well understood. The current research examined nicotine metabolism rate as a risk factor for alcohol use among current tobacco users. We also examined sex differences in these associations. METHOD: Data were taken from Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study, a national longitudinal study of tobacco use and associated health outcomes. The nicotine metabolite ratio (NMR) was calculated as the ratio of trans-3' hydroxycotinine to cotinine in urine samples provided at wave 1. Alcohol use outcomes included past 30-day NIAAA-defined hazardous drinking status, total drinks, and alcohol-related consequences. All analyses controlled for alcohol use at Wave 1. RESULTS: NMR at Wave 1 predicted increased odds of meeting hazardous drinking criteria, adjusted odds ratio (aOR) = 1.14, 95 % CI = 1.06; 1.23, p = 0.001, greater total alcohol consumption amount, adjusted rate ratio (aRR) = 1.21, 95 % CI = 1.12; 1.30, p < 0.001, and more alcohol consequences, aRR = 1.07, 95 % CI = 1.01; 1.13, p = 0.018, at wave 2. No significant sex differences were identified. NMR remained a significant predictor of alcohol use in models controlling for severity of nicotine exposure in cigarette smokers. CONCLUSIONS: NMR may be a shared risk factor for harmful nicotine and alcohol use that contributes to their co-occurrence.

Changes in excessive alcohol use among older women across the menopausal transition: a longitudinal analysis of the Study of Women's Health Across the Nation.

BACKGROUND: Recent data suggest that excessive alcohol use is increasing among women and older adults. Such trends are concerning, as women are more vulnerable to alcohol-related health consequences, and such health problems may be exacerbated with age. Furthermore, there are sex-specific factors that may influence alcohol consumption among women, including the hormonal changes associated with the menopausal transition and negative affect. The present study sought to investigate transitions in excessive drinking among women across the menopausal transition and included exploration of sex hormones (estradiol; testosterone) and depression. METHODS: The present study utilized publicly available data from the Study of Women Across the Nation (SWAN) and included 3302 women (42-52 years old at baseline), who completed 10 years of annual assessments. National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria were used as guidance when defining excessive drinking within the present dataset. At year 1, 170 women were identified as drinking excessively. Random-effect logistic regressions were used to examine transitions in excessive drinking. RESULTS: Women identified as excessive drinkers were more likely to transition to non-excessive drinking across all menopausal transition stages (ORs range = 3.71-5.11), while women were more likely to transition from non-excessive to excessive drinking during the early peri- and postmenopausal stages (OR = 1.52 and 1.98, respectively). Higher testosterone levels were associated with a decreased likelihood of transitioning to non-excessive drinking (OR = 0.59). Depression and estradiol levels were not related to transitions in drinking. CONCLUSIONS: The present study demonstrates that the menopausal transition marks a period of instability in alcohol use among women. Further research is warranted to understand factors related to transitioning in and out of excessive drinking.

Associations Between Nicotine Metabolite Ratio and Gender With Transitions in Cigarette Smoking Status and E-Cigarette Use: Findings Across Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: Nicotine metabolite ratio (NMR), the ratio of trans 3'-hydroxycotinine to cotinine, is a biomarker of nicotine metabolism. Discrepant findings among clinical trials and population-based studies warrant replication on whether higher NMR, or faster nicotine metabolism, is associated with quitting cigarette smoking. Associations of NMR and e-cigarette use are largely unknown, as well as the relationship between NMR and gender on quitting cigarette smoking or e-cigarette use. METHODS: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal cohort study assessing tobacco use in the US population. In the current study, the PATH (waves 1 and 2; adult interviews) was used to evaluate longitudinal predictions in relationships among NMR and gender and their association with transitions (quit vs. current stable) in cigarette smoking status and e-cigarette use status across waves 1 and 2 of the PATH study. RESULTS: NMR and gender were not significantly associated with quit behavior for combustible cigarettes. Regarding e-cigarettes, a significant two-way interaction demonstrated that women with higher NMR were less likely to quit e-cigarette use compared to women with lower NMR (odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.02-0.57; p = .01). CONCLUSIONS: Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism across waves 1 and 2 of the PATH study. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women. IMPLICATIONS: Findings identify that women with faster nicotine metabolism were 10 times less likely to quit e-cigarettes compared to women with slower nicotine metabolism. Results suggest that NMR may be used as a biomarker for transitions in e-cigarette quit behavior for women. Establishing parameters for NMR collection and for the use of NMR as a biomarker for cigarette smoking behavior and e-cigarette use is an important next step, and may have implications for early intervention and treatment for cessation.