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

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

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 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 \u3c 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD (OR = 2.10, p \u3c 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 \u3c 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD (OR = 1.40, 1.70, respectively; p \u3c 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/seda-tives/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

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

Intersection of Stress and Gender in Association With Transitions in Past Year DSM-5 Substance Use Disorder Diagnoses in the United States

Background Stress contributes to the development and maintenance of substance use disorders, with some research suggesting that the impact of stress on substance use disorders is greater in women. However, this has yet to be evaluated in a national dataset, across major substances of abuse. Methods Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n  = 36,309), we evaluated relationships among past year stressful life events (0 or 1 vs. 2+ events, range 0–16) and gender, and their association with transitions (new vs. absent cases; ongoing vs. remitted cases) in Diagnostic and Statistical Manual of Mental Disorders Fifth Edition alcohol use disorder, tobacco use disorder, cannabis use disorder, and nonmedical prescription opioid use disorder diagnoses. Results Having two or more stressful life events in the past year increased the odds of having a new alcohol use disorder, tobacco use disorder, cannabis use disorder, and opioid use disorder (OR = 3.14, 2.15, 5.52, and 3.06, respectively) or ongoing alcohol use disorder, tobacco use disorder, and cannabis use disorder (OR = 2.39, 2.62, and 2.95, respectively) compared to zero or one stressful life event. A stress by gender interaction for new vs. absent alcohol use disorder demonstrated that having two or more stressful life events was associated with increased odds of new alcohol use disorder in men (OR = 2.51) and even greater odds of new alcohol use disorder in women (OR = 3.94). Conclusions Results highlight that stress is a robust factor in both men and women with new or ongoing substance use disorders, and that effective treatments for substance use should consider the role of stress in addiction etiology and maintenance. There was little evidence for gender differences in the role of stress on transitions in substance use disorders, except for the onset of alcohol use disorders. Given that rates of alcohol use disorders are increasing in women, the impact of stress needs to be considered

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 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-HSD1 inhibitor radiotracer [18F]AS2471907 as a bolus injection and were imaged for 150–180 min on the High-Resolution Research Tomograph. 11β-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 11β-HSD1 availability in individuals with AUD. Our data suggest higher brain availability of the cortisol-regenerating enzyme 11β-HSD1 in people with AUD (vs. controls), and that higher vmPFC 11β-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

Psychiatric Disorders and Crime in the US Population: Results From the National Epidemiologic Survey on Alcohol and Related Conditions Wave III

Objective: Current knowledge regarding the intersection of psychiatric disorders and crime in the United States is limited to psychiatric, forensic, and youth samples. This study presents nationally representative data on the relationship of DSM-5 psychiatric disorders, comorbid substance and mental health disorders, and multimorbidity (number of disorders) with criminal behavior and justice involvement among non-institutionalized US adults. Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions Wave III (NESARC-III; 2012-2013; N = 36,309). Logistic regressions were used to examine the association of specific disorders (eg, mood, anxiety, eating, posttraumatic stress, substance use), comorbid substance use and mental health disorders, and multimorbidity with lifetime criminal behavior, incarceration experience, and past-12-month general, alcohol-related, and drug-related legal problems. Results: Overall, 28.5% of participants reported a history of criminal behavior, 11.4% reported a history of incarceration, 1.8% reported current general legal problems, 0.8% reported current alcohol-related legal problems, and 2.7% reported current drug-related legal problems. The presence of any disorder was associated with a 4 to 5 times increased risk of crime outcomes. Drug use disorders were associated with the highest risk of lifetime crime (adjusted odds ratio [AOR] = 6.8; 95% CI, 6.1-7.6) and incarceration (AOR = 4.7; 95% CI, 4.1-5.3) and current legal problems (AOR = 3.3; 95% CI, 2.6-4.2). Multimorbidity and comorbid substance use and mental health disorders were associated with additional risk. Controlling for antisocial personality disorder did not change the findings. Conclusions: Community adults with substance use disorders, comorbid substance use and mental health disorders, and increasing multimorbidity are most at risk of crime and justice involvement, highlighting the importance of community-based addiction treatment