Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

A Brief Screening Tool for Risk of Self-Medication of Pain With Substance Use.

OBJECTIVES: Substance use and pain are both growing public health concerns globally. Evidence suggests that individuals may use substances in order to self-medicate their pain. The Catastrophizing, Anxiety, Negative Urgency, and Expectancy model was developed to provide a theoretical foundation for the modifiable risk factors implicated in self-medication of pain with substance use. This study aimed to use the outcomes in the Catastrophizing, Anxiety, Negative Urgency, and Expectancy model to develop a brief clinical screening tool to identify individuals at risk for self-medication. METHODS: Participants (N = 520; M age = 38.8) were adults who endorsed the past three-month use of at least one substance and completed an online questionnaire. Logistic regression and receiver operator characteristic analyses were used to reduce the initial 104-item questionnaire to the items needed to achieve a minimum accuracy score of 0.95 and 0.90. RESULTS: A 14-item and a 7-item questionnaire were derived from the initial larger questionnaire. Both of these questionnaires were significantly correlated with the outcome variables and were significantly associated with health risk and percent of use because of pain. The R2 values between the 14- and 7-item versions were only significantly different for the percent of alcohol use because of pain. CONCLUSIONS: The study provides two brief screening tools to screen for individuals at risk for self-medication of pain with substance use that can be easily implemented within clinical settings. Further, the screening tools provide insight into modifiable risk factors for self-medication and may also be valuable to monitor treatment response.

Metformin Cessation and Dementia Incidence.

Importance: Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin. Objective: To investigate the association of terminating metformin treatment for reasons unrelated to kidney dysfunction with dementia incidence. Design, Setting, and Participants: This cohort study was conducted at Kaiser Permanente Northern California, a large integrated health care delivery system, among a cohort of metformin users born prior to 1955 without history of diagnosed kidney disease at metformin initiation. Dementia follow-up began with the implementation of electronic health records in 1996 and continued to 2020. Data were analyzed from November 2021 through September 2023. Exposures: A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration. Main outcomes and measures: The outcome of interest was all-cause incident dementia. Follow-up for early terminators and their matched routine users was started at age of termination for the early terminator. Survival models adjusted for sociodemographic characteristics and comorbidities at the time of metformin termination (or matched age). Mediation models with HbA1c level and insulin usage 1 and 5 years after termination tested whether changes in blood glucose or insulin usage explained associations between early termination of metformin and dementia incidence. Results: The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage. Conclusions and Relevance: In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan.

BACKGROUND AND OBJECTIVES: The associations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model nonlinearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data. METHODS: Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia before the survey, and had laboratory measurements of cholesterol within 2 years after survey completion were followed up through December 2020 for incident dementia (Alzheimer disease-related dementia [ADRD]; Alzheimer disease, vascular dementia, and/or nonspecific dementia) based on ICD-9 or ICD-10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years postsurvey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated nonlinearities using B-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use. RESULTS: A total of 184,367 participants [mean age at survey = 69.5 years, mean HDL-C = 53.7 mg/dL (SD = 15.0), mean LDL-C = 108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared with the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI 1.03-1.11), and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI 1.11-1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with a slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase = 1.01, 95% CI 1.01-1.02) and a lower risk for nonusers (HR per 10 mg/dL increase = 0.98; 95% CI 0.97-0.99). There was evidence for effect modification by age with linear HDL-C (p = 0.003) but not LDL-C (p = 0.59). DISCUSSION: Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.

The association between prescription drug monitoring programs and controlled substance prescribing: a cross-sectional study using data from 2019 National Electronic Health Records Survey.

OBJECTIVE: The use of controlled medications such as opioids, stimulants, anabolic steroids, depressants, and hallucinogens has led to an increase in addiction, overdose, and death. Given the high attributes of abuse and dependency, prescription drug monitoring programs (PDMPs) were introduced in the United States as a state-level intervention. MATERIALS AND METHODS: Using cross-sectional data from the 2019 National Electronic Health Records Survey, we assessed the association between PDMP usage and reduced or eliminated controlled substance prescribing as well as the association between PDMP usage and changing a controlled substance prescription to a nonopioid pharmacologic therapy or nonpharmacologic therapy. We applied survey weights to produce physician-level estimates from the survey sample. RESULTS: Adjusting for physician age, sex, type of medical degree, specialty, and ease of PDMP, we found that physicians who reported "often" PDMP usage had 2.34 times the odds of reducing or eliminating controlled substance prescriptions compared to physicians who reported never using the PDMP (95% confidence interval [CI] 1.12-4.90). Adjusting for physician age, sex, type of doctor, and specialty, we found that physicians who reported "often" use of the PDMP had 3.65 times the odd of changing controlled substance prescriptions to a nonopioid pharmacologic therapy or nonpharmacologic therapy (95% CI: 1.61-8.26). DISCUSSION: These results support the continued use, investment, and expansion of PDMPs as an effective intervention for reducing controlled substance prescription and changing to nonopioid/pharmacologic therapy. CONCLUSION: Overall, frequent usage of PDMPs was significantly associated with reducing, eliminating, or changing controlled substance prescription patterns.

Pain Acceptance Among Retired National Football League Athletes: Implications for Clinical Intervention.

Over 80% of National Football League (NFL) retirees experience daily pain. Pain acceptance is an important psychological construct implicated in the intensity of chronic pain, though these findings have not been extended to NFL retirees. Therefore, the current study examined the association between pain acceptance and pain intensity among former NFL athletes. NFL retirees (N = 90) recruited from 2018 to 2019 completed questionnaires that assessed pain, substance use, and NFL career information. Multiple linear regression examined the association between current pain acceptance and pain intensity while adjusting for other risk factors of pain. NFL retirees reported average scores of 33.31 (SD = 10.00), and 2.18 (SD = 2.40) on measures of pain acceptance and pain intensity, respectively. After covariate adjustment, greater pain acceptance (ß = -0.538, p < .001) was associated with lower pain intensity. These findings can further inform the behavioral and mental health care of retired NFL athletes.

Association of therapeutic and recreational reasons for alcohol use with alcohol demand.

Motives for alcohol use and behavioral economic measures of demand are associated with alcohol consumption and alcohol-related problems. However, it is unclear how differences in reasons for alcohol use may affect alcohol demand. Additionally, although alcohol is commonly used to self-manage conditions such as pain and sleep problems, the impact of these reasons for alcohol use on alcohol demand is not well characterized. The present study addressed this gap. Participants were adults recruited via Amazon Mechanical Turk as part of a larger study investigating health behaviors. Analyses included participants who reported alcohol use in the past year (N = 637). Participants were categorized as having recreational, therapeutic, or both recreational and therapeutic reasons for using alcohol. A brief, three-item measure of alcohol demand was administered. Multivariate analysis of variance (MANOVA) analyses revealed that alcohol drinkers endorsing both recreational and therapeutic reasons for use had significantly higher average intensity, Omax, and breakpoint indices compared to those who only reported recreational or therapeutic drinking motives (ps < .05; Cohen's d = .09-.17). Secondary analyses revealed differences in demand according to therapeutic reason for alcohol use endorsed. Significant main effects were found for use to relieve pain and anxiety/depression/stress, while interactive effects were detected for use to relieve pain and improve sleep and use to relieve pain and anxiety/depression/stress. Overall, results suggest that alcohol demand is highest in drinkers who consume alcohol for both therapeutic and recreational reasons. This group may be at elevated risk for alcohol use disorder and alcohol-related consequences. Continued research is necessary to examine this possibility. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reliability of an adaptive marijuana purchase task.

Purchase tasks are used to measure the value, or demand, for various substances by assessing the amount of a substance individuals would purchase across a series of escalating prices. Marijuana purchase task (MPT) has been previously developed; however, cannabis can be consumed in various forms and measurements, thus raising questions about the applicability of the MPT across cannabis users. An adaptive MPT was developed to allow participants to select their preferred product (e.g., herbal, dabs) and division (e.g., hits, grams). Little research has been done to assess the temporal stability of these measures. Participants (N = 50, Mage = 35.3) who reported at least monthly cannabis use were recruited via Amazon's Mechanical Turk and completed a baseline and repeated original and adaptive MPT. Seventy-two percent (N = 36) of the sample reported the same preferred product and division. Results indicated that the baseline and repeated original MPT were significantly correlated across all indices (rrange = .37-.73), while the baseline and repeated adaptive MPT was significantly correlated with Pmax (r = .31, p = .029) and Omax (r = .57, p < .001). Permutation testing comparing the difference between the original and adaptive MPT on all indices demonstrated a difference for break point (rdifference = .52, p = .004) and elasticity (rdifference = .94, p = .005). Correlations were lower between participants who switched their preferences on the adaptive MPT. Only elasticity was significantly different (rdifference = .93, p = .012) between tasks among participants who did not switch their preferences. Results provide support that both the original and adaptive MPT are reliable across repeated measurement and demonstrate the importance of assessing cannabis product and division preferences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Longitudinal associations between pain and substance use disorder treatment outcomes.

INTRODUCTION: Pain is commonly reported among those in treatment for substance use disorders (SUD) and is associated with poorer SUD treatment outcomes. The current study examined the trajectory of pain over the course of SUD treatment and associations with substance use outcomes. METHODS: This observational study included adults seeking treatment for alcohol, cannabis, or opioid use disorders (N = 811). Participants completed a battery of assessments at treatment admission, 30 days post admission, and at discharge, including measures of demographics, pain, quality of life, abstinence self-efficacy, and craving. RESULTS: Analyses indicated linear reductions in pain intensity and interference over time. Significant interactive effects were observed for opioid use disorder (OUD) and time, such that participants with OUD had greater reductions in pain intensity and interference over time compared to those without OUD. Elevated pain intensity was associated with negative treatment outcomes, including reduced quality of life and abstinence self-efficacy, and greater craving and negative affect. CONCLUSIONS: Reductions in pain occur over the course of SUD treatment, particularly for those with OUD. Greater pain was also associated with adverse SUD treatment outcomes. Results suggest that treatment and associated abstinence may be beneficial for those with co-occurring pain and SUD, highlighting an additional benefit of improving access to SUD treatment for patients and health care systems. Future research should replicate these findings among diverse samples and further characterize the trajectory of pain during and after SUD treatment.

Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.

Sex differences in associations between delay discounting and expectancies for alcohol analgesia.

Self-medication of pain with alcohol is prevalent, and expectancies for alcohol analgesia likely influence pain relief and alcohol consumption. Hazardous alcohol use has been associated with greater delay discounting rates; however, little is known about the relationship between delay discounting and expectancies for alcohol analgesia. Therefore, the present study examined sex differences in associations between delay discounting and expectancies for alcohol analgesia. Healthy drinkers without chronic pain (N = 53) completed measures of expectancies for alcohol analgesia, alcohol use, and alcohol outcome expectancies. A five-trial adjusting-delay discounting task (DDT) for monetary outcomes was also administered. Regression analyses revealed that sex moderated the relationship between delay discounting and expectancies for alcohol analgesia. Steeper delay discounting rates were associated with weaker expectancies for alcohol analgesia among men when adjusting for average alcohol consumption. Among women, nonsignificant associations between delay discounting rates and expectancies for alcohol analgesia were observed. These findings provide initial evidence of sex differences in associations between delay discounting and expectancies for alcohol analgesia. The directionality of these associations was unexpected and may have implications for patterns of self-medication with alcohol. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sex-specific mechanisms of tolerance for the cannabinoid agonists CP55,940 and delta-9-tetrahydrocannabinol (Δ9-THC).

RATIONALE: Tolerance to cannabinoids could limit their therapeutic potential. Male mice expressing a desensitization-resistant form (S426A/S430A) of the type-1 cannabinoid receptor (CB1R) show delayed tolerance to delta-9-tetrahydrocannabinol (∆9-THC) but not CP55,940. With more women than men using medical cannabis for pain relief, it is essential to understand sex differences in cannabinoid antinociception, hypothermia, and resultant tolerance. OBJECTIVE: Our objective was to determine whether female mice rely on the same molecular mechanisms for tolerance to the antinociceptive and/or hypothermic effects of cannabinoids that we have previously reported in males. We determined whether the S426A/S430A mutation differentially disrupts antinociceptive and/or hypothermic tolerance to CP55,940 and/or Δ9-THC in male and female S426A/S430A mutant and wild-type littermates. RESULTS: The S426A/S430A mutation conferred an enhanced antinociceptive response for ∆9-THC and CP55,940 in both male and female mice. While the S426A/S430A mutation conferred partial resistance to ∆9-THC tolerance in male mice, disruption of CB1R desensitization had no effect on tolerance to ∆9-THC in female mice. The mutation did not alter tolerance to the hypothermic effects of ∆9-THC or CP55,940 in either sex. Interestingly, female mice were markedly less sensitive to the antinociceptive effects of 30 mg/kg ∆9-THC and 0.3 mg/kg CP55,940 compared with male mice. CONCLUSIONS: Our results suggest that disruption of the GRK/ßarrestin2 pathway of desensitization alters tolerance to Δ9-THC but not CP55,940 in male but not female mice. As tolerance to Δ9-THC appears to develop differently in males and females, sex should be considered when assessing the therapeutic potential and dependence liability of cannabinoids.

The effect of next day responsibilities and an adaptive purchase task on cannabis demand.

BACKGROUND: The marijuana purchase task (MPT) is a commonly used behavioral economic measure of relative cannabis value (i.e. demand) that presents specific methodological concerns due to non-standardized measurement, variability in modality of use, and evolving legalization policies. Refinement of the task is critical to improve task ecological validity and accurate measurement of cannabis demand. The present study examined the construct validity of an adaptive MPT that allowed for participant selection of their preferred cannabis-based product and unit of measurement and the effect of next-day responsibilities on demand. METHODS: Participants reporting at least monthly cannabis use (N = 186, 40.3 % women, Mage = 33.59) were recruited via Amazon Mechanical Turk and completed the original MPT and our adaptive form with 2 next-day responsibilities scenarios (no responsibilities vs. morning job interview) for each MPT. Cannabis use motives, problems, and risk for cannabis use disorder were also assessed. RESULTS: Cannabis demand was sensitive to next-day responsibility, with higher hypothetical consumption observed in the no responsibilities condition. Responsibility-related decreases in Omax (F(1,185) = 4.83, p = .029, η2p = .03) were significantly greater on the adaptive MPT than the original MPT. Demand indices derived from the adaptive MPT were significantly correlated with cannabis problems (rbreakpoint = .19, rPmax = 0.18, relasticity=-0.18) and motives (rrange=-.32-.25), and demand metrics from the original MPT. CONCLUSIONS: Results provide preliminary support for the construct validity of an adaptive MPT and suggest that early-morning work responsibilities may reduce cannabis demand. Continued research is needed to further refine this task and determine implications for cannabis use disorder intervention and prevention approaches.

Acute Tolerance to the Analgesic Effects of Alcohol.

OBJECTIVE: The goal of this study was to determine whether the acute analgesic effects of alcohol intake are moderated by acute alcohol tolerance, characterized by differing subjective and neurobehavioral effects of a given blood alcohol concentration (BAC) depending on whether BAC is rising or falling. METHOD: Twenty-nine healthy drinkers (20 women) completed two laboratory sessions in which they consumed a study beverage: active alcohol (target BAC= .08 g/dl) and placebo. Acute alcohol tolerance was assessed by examining the main and interactive effects of beverage condition and assessment limb (ascending vs. descending) on quantitative sensory testing measures collected using slowly ramping heat stimuli and perceived relief ratings at comparable breath alcohol concentrations on the ascending and descending limbs. RESULTS: BAC limb moderated the effect of condition on pain threshold, such that the threshold was significantly elevated in the alcohol condition on the ascending limb. The alcohol condition produced greater ratings of perceived pain relief than the placebo condition, and pain relief ratings were greater on the ascending versus descending limb of the BAC curve. Alcohol intake did not significantly affect pain tolerance or aftersensation ratings on either BAC limb. CONCLUSIONS: This study provides initial experimental evidence that alcohol's analgesic and pain-relieving effects are subject to acute tolerance following acute alcohol intake. These findings suggest that self-medicating pain via alcohol intake may be associated with high-risk drinking topography, increasing the risk for alcohol-related consequences. Further research is needed to determine if these effects extend to the context of clinical and chronic pain.

Sex moderates the effects of experimentally induced musculoskeletal pain on alcohol demand in healthy drinkers.

BACKGROUND: Pain may serve as an antecedent for alcohol use, increasing risk for hazardous drinking and associated consequences. Delayed onset muscle soreness (DOMS) induction produces clinically relevant but time-limited musculoskeletal pain. This study was conducted to determine whether DOMS induction on the dominant elbow flexors influenced alcohol demand using the Alcohol Purchase Task (APT). We hypothesized DOMS would increase alcohol demand relative to a sham control. Based on existing studies of pain self-medication, we expected DOMS-related increases in alcohol demand would be greatest in men. METHODS: Participants (N = 53; 57 % women) were randomly assigned to a DOMS (eccentric exercise) or sham condition (concentric exercise). Participants completed the APT pre-exercise and 48 -hs post-exercise. Repeated measures GLM was used to characterize group by sex by time interactions on APT indices, including intensity, breakpoint, essential value (EV), Omax, and Pmax. RESULTS: The DOMS procedure significantly increased pain ratings at the elbow flexors. Men had significantly higher demand intensity than women across groups and time points. Significant interactive effects were detected for breakpoint and EV. From pre- to post-test, breakpoint significantly increased in men in the DOMS group. However, breakpoint and EV significantly decreased in women in the DOMS group. CONCLUSIONS: Increased alcohol demand in men in the DOMS group was consistent with epidemiological data suggesting men are at higher risk for self-medicating pain with alcohol than women. However, decreased demand in women was unexpected. Taken together, results indicate DOMS induction may be a useful means to characterize pain as an antecedent for alcohol use.

CANUE: A Theoretical Model of Pain as an Antecedent for Substance Use.

BACKGROUND: Pain and substance use are frequently comorbid and have been shown to exert bidirectional effects. Self-medication of pain and distress via substance use is common and can be understood via negative reinforcement, ultimately strengthening the pathway between pain to substance use over time. As such, a testable model of the potentially modifiable candidate mechanisms that underlie the pain to substance use pathway is needed. PURPOSE: This review proposes a testable model of pain as an antecedent to substance use to guide future research and inform clinical practice. METHODS: An integrative review of current evidence regarding pain, substance use, and associated risk factors (i.e., negative affect, pain-related attitudes, negative urgency, and substance use outcome expectancies) was conducted. RESULTS: The Catastrophizing, Anxiety, Negative Urgency, and Expectancy (CANUE) model highlights modifiable risk factors for self-medicating pain with substance use, including increased negative affect and maladaptive pain-related attitudes (i.e., pain catastrophizing, pain anxiety, and fear of pain), negative urgency, and substance-related outcome expectancies for pain relief and enhanced pain coping. CONCLUSIONS: Targeted behavioral and psychological interventions that address these factors may facilitate more adaptive pain-coping responses, thereby reducing the impacts of pain on substance use. Systematic research is needed to evaluate the validity and clinical utility of this model.

Symptoms of generalized anxiety disorder as a risk factor for substance use among adults living with HIV.

This study examined the association between symptoms of generalized anxiety disorder (GAD) and substance use among 932 people living with HIV (PLWH) in Florida. PLWH completed a 45-minute questionnaire assessing demographics, symptoms of GAD and depression, and use of substances including alcohol, cigarettes, marijuana, crack/cocaine, and injection drugs. The GAD-7 measured symptoms of anxiety and participants were categorized as experiencing none/mild anxiety (score 0-9) or moderate/severe symptoms (score ≥10). Adjusted binary logistic regressions assessed the association between moderate-severe GAD symptoms and substance use while controlling for covariates, including depressive symptoms. Approximately one-third (31.4%) of the sample reported experiencing moderate/severe symptoms of GAD. After controlling for covariates, PLWH with moderate/severe symptoms of GAD had greater odds of reporting current cigarette use (AOR = 1.70, 95% CI = 1.18-2.45 p = 0.004), past 30-day hazardous alcohol consumption (AOR = 1.50, 95% CI = 1.04-2.16, p = 0.028), and past 12-month non-injection crack/cocaine use (AOR = 1.75, 95% CI = 1.13-2.69, p = 0.011) compared to PLWH reporting none/mild symptoms. Findings demonstrate that moderate/severe GAD symptoms were common among this sample of PLWH in Florida and were associated with use of cigarettes, crack/cocaine, and hazardous alcohol consumption. Future studies should explore interventions to reduce comorbid anxiety and substance use.

History of opioid use as a risk factor for current use and mental health consequences among retired National Football League athletes: A 9-year follow-up investigation.

BACKGROUND: Many retired National Football League (NFL) athletes manage pain with opioids during their playing careers and in retirement, though the longitudinal association between opioid use and health outcomes pertinent to an NFL career are not yet known. This study aimed to assess the relationship between opioid use in 2010 and current use, depressive symptoms, and health related quality of life (HRQoL) among NFL retirees. METHODS: Former NFL athletes from the Retired NFL Players Association initially recruited in 2010 for a study examining risk factors of opioid use and misuse were re-contacted (N = 89) from 2018 to 2019 and administered measures of pain, opioid use, depressive symptoms, and HRQoL. Binomial regression examined the association between 2010 opioid use with current use, moderate-severe depressive symptoms, and average and above HRQoL (physical and mental) while controlling for covariates. RESULTS: Nearly 50 % of retirees using opioids in 2010 currently used. Compared to non-users, retirees who used opioids in 2010 had greater odds of current use (AOR: 3.71, 95 % CI: 1.02-13.56, p = 0.046) and experiencing moderate-severe depressive symptoms (AOR: 5.93, 95 % CI: 1.15-30.54, p = 0.033). Retirees reporting use in 2010 also evidenced lower odds of reporting average or above mental HRQoL (AOR: 0.13, 95 % CI: 0.03-0.67, p = 0.015) compared to non-users. CONCLUSIONS: This study showed that among NFL retirees, early retirement opioid use predicted current use and deleterious effects on mental health, including moderate-severe depressive symptoms approximately nine years later. This investigation further supports the importance of early intervention of pain and opioid use among this population.

Negative health consequences of pain catastrophizing among retired National Football League athletes.

OBJECTIVE: This study examined the association between pain catastrophizing with pain interference, depressive symptoms, and health-related quality of life (HRQoL) among National Football League (NFL) retirees. METHOD: Former NFL athletes from the Retired NFL Players Association (N = 90) were recruited from 2018 to 2019 via telephone and were administered measures of pain, substance use, depressive symptoms, and HRQoL. Multiple linear and binomial regression analyses examined the association of pain catastrophizing with pain interference, depressive symptoms, and HRQoL while controlling for covariates (i.e., pain intensity, concussions, opioid use, binge alcohol use, years since NFL retirement, and marital status). RESULTS: Many retired NFL athletes reported moderate-severe depressive symptoms as well as poorer perceived physical health compared with general medical patients. Greater pain catastrophizing was associated with more severe pain interference, greater odds of reporting moderate-severe depressive symptoms, and lower odds of reporting average and above physical and mental HRQoL after adjusting for relevant covariates. Concussions were not associated with any of the study outcomes. CONCLUSIONS: Given the findings from this study, health care professionals should monitor symptoms of catastrophizing among current and retired NFL athletes. Assessment and requisite treatment of pain catastrophizing may assist these elite athletes in reducing depressive symptoms, while improving pain interference and HRQoL in this population. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Prevalence and Correlates of Psychological Distress among Retired Elite Athletes: A Systematic Review.

This article presents results of a systematic review of the literature (2000-2017) examining the prevalence and correlates of psychological distress among retired elite athletes. Forty articles were selected and included. Our review suggests the prevalence of psychological distress among retired athletes is similar to that found in the general population. However, subgroups reporting medical comorbidities, significant pain, a greater number of concussions, less social support, and adverse psychosocial factors were at greater risk for psychological distress. Additionally, athletes experiencing psychological distress in retirement often do not seek treatment for their distress. Based on the existing literature, there is a need for greater standardization and use of reliable measures, as well as use of diagnostic interviews in order to assess the most accurate prevalence of psychological distress among these athletes. Longitudinal designs, matched control groups, more heterogeneous samples, and use of multivariate analyses would also help to more accurately determine the prevalence and risk factors of psychological distress in this population. This review suggests a number of different clinical implications and highlights directions for future research to enhance our understanding of the long-term psychological health of former elite athletes.