Clarifying the relationship between mental illness and recidivism using machine learning: A retrospective study.

OBJECTIVE: There is currently inconclusive evidence regarding the relationship between recidivism and mental illness. This retrospective study aimed to use rigorous machine learning methods to understand the unique predictive utility of mental illness for recidivism in a general population (i.e.; not only those with mental illness) prison sample in the United States. METHOD: Participants were adult men (n = 322) and women (n = 72) who were recruited from three prisons in the Midwest region of the United States. Three model comparisons using Bayesian correlated t-tests were conducted to understand the incremental predictive utility of mental illness, substance use, and crime and demographic variables for recidivism prediction. Three classification statistical algorithms were considered while evaluating model configurations for the t-tests: elastic net logistic regression (GLMnet), k-nearest neighbors (KNN), and random forests (RF). RESULTS: Rates of substance use disorders were particularly high in our sample (86.29%). Mental illness variables and substance use variables did not add predictive utility for recidivism prediction over and above crime and demographic variables. Exploratory analyses comparing the crime and demographic, substance use, and mental illness feature sets to null models found that only the crime and demographics model had an increased likelihood of improving recidivism prediction accuracy. CONCLUSIONS: Despite not finding a direct relationship between mental illness and recidivism, treatment of mental illness in incarcerated populations is still essential due to the high rates of mental illnesses, the legal imperative, the possibility of decreasing institutional disciplinary burden, the opportunity to increase the effectiveness of rehabilitation programs in prison, and the potential to improve meaningful outcomes beyond recidivism following release.

Acceptability of Personal Sensing Among People With Alcohol Use Disorder: Observational Study.

BACKGROUND: Personal sensing may improve digital therapeutics for mental health care by facilitating early screening, symptom monitoring, risk prediction, and personalized adaptive interventions. However, further development and the use of personal sensing requires a better understanding of its acceptability to people targeted for these applications. OBJECTIVE: We aimed to assess the acceptability of active and passive personal sensing methods in a sample of people with moderate to severe alcohol use disorder using both behavioral and self-report measures. This sample was recruited as part of a larger grant-funded project to develop a machine learning algorithm to predict lapses. METHODS: Participants (N=154; n=77, 50% female; mean age 41, SD 11.9 years; n=134, 87% White and n=150, 97% non-Hispanic) in early recovery (1-8 weeks of abstinence) were recruited to participate in a 3-month longitudinal study. Participants were modestly compensated for engaging with active (eg, ecological momentary assessment [EMA], audio check-in, and sleep quality) and passive (eg, geolocation, cellular communication logs, and SMS text message content) sensing methods that were selected to tap into constructs from the Relapse Prevention model by Marlatt. We assessed 3 behavioral indicators of acceptability: participants' choices about their participation in the study at various stages in the procedure, their choice to opt in to provide data for each sensing method, and their adherence to a subset of the active methods (EMA and audio check-in). We also assessed 3 self-report measures of acceptability (interference, dislike, and willingness to use for 1 year) for each method. RESULTS: Of the 192 eligible individuals screened, 191 consented to personal sensing. Most of these individuals (169/191, 88.5%) also returned 1 week later to formally enroll, and 154 participated through the first month follow-up visit. All participants in our analysis sample opted in to provide data for EMA, sleep quality, geolocation, and cellular communication logs. Out of 154 participants, 1 (0.6%) did not provide SMS text message content and 3 (1.9%) did not provide any audio check-ins. The average adherence rate for the 4 times daily EMA was .80. The adherence rate for the daily audio check-in was .54. Aggregate participant ratings indicated that all personal sensing methods were significantly more acceptable (all P<.001) compared with neutral across subjective measures of interference, dislike, and willingness to use for 1 year. Participants did not significantly differ in their dislike of active methods compared with passive methods (P=.23). However, participants reported a higher willingness to use passive (vs active) methods for 1 year (P=.04). CONCLUSIONS: These results suggest that active and passive sensing methods are acceptable for people with alcohol use disorder over a longer period than has previously been assessed. Important individual differences were observed across people and methods, indicating opportunities for future improvement.

Alcohol's effects during uncertain and uncontrollable stressors in the laboratory.

Alcohol's effects on reactivity to stressors depends on the nature of the stressor and the reactivity being assessed. Research identifying characteristics of stressors that modulate reactivity and clarifies the neurobehavioral, cognitive, and affective components of this reactivity may help prevent, reduce or treat the negative impacts of acute and chronic alcohol use with implications for other psychopathology involving maladaptive reactivity to stressors. We used a novel, multi-measure, cued electric shock stressor paradigm in a greater university community sample of adult recreational drinkers to test how alcohol (N=64), compared to No-alcohol (N=64), effects reactivity to stressors that vary in both their perceived certainty and controllability. Preregistered analyses suggested alcohol significantly dampened subjective anxiety (self-report) and defensive reactivity (startle potentiation) more during uncertain than during certain stressors regardless of controllability, suggesting that stressor uncertainty -but not uncontrollability- may be sufficient to enhance alcohol's stress reactivity dampening and thus negative reinforcement potential.

Central stress response among deprived and continuing marijuana users and nonusers.

OBJECTIVE: We examined central nervous system [CNS] stress responses among deprived and continuing heavy marijuana users and nonusers. METHOD: Participants (N = 210; 46.7% female; Mage = 21.99; 91.4% White, 94.3% Non-Hispanic) were heavy marijuana users (N = 134) and nonusers (N = 76). Heavy users were randomly assigned to a 3-day marijuana deprivation condition (N = 68) or to continue using regularly (N = 66). Participants completed two threat-of-shock stressor tasks that manipulated stressor predictability by varying shock probability or timing. We measured central stress responses via startle potentiation (stressor conditions minus matched no-stressor condition). We examined two group contrasts (heavy use: all heavy users vs. nonusers; deprivation: deprived vs. continuing heavy users) on startle potentiation overall and moderated by stressor predictability (unpredictable vs. predictable). RESULTS: Deprivation did not affect startle potentiation overall (timing task: p = .184; probability task: p = .328) or differently by stressor predictability (timing task: p = .147; probability task: p = .678). Heavy use did not affect startle potentiation overall (timing task: p = .213; probability task: p = .843) or differently by stressor predictability (timing task: p = .655; probability task: p = .273). Posthoc analyses showed mixed evidence of general startle reactivity × deprivation interaction on startle potentiation overall (timing task: p = .019; probability task: p = .056) and differently by stressor predictability (probability task: p = .024; timing task: p = .364). CONCLUSIONS: A history of marijuana use or acute deprivation did not alter central stress responses despite prominent theoretical expectations. This study adds to growing research on central stress responses in individuals with a history of drug use and begins to parse moderating roles of individual differences and stressor characteristics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Stressor-elicited smoking and craving during a smoking cessation attempt.

Stressors can undermine smokers' attempts to quit smoking. Although contemporary theories and animal models support this idea, human research has struggled to demonstrate definitively the relationship between stressors and smoking. Researchers have employed more ecologically valid methods like ecological momentary assessment to address this question, but studies focusing explicitly on stressors remain sparse and findings inconsistent. The purpose of this study was to examine the effect of stressful event intensity on smoking and craving among cigarette smokers during a quit attempt. We conducted preregistered, complementary concurrent and prospective (i.e., 8-hour lag window between stressful event and outcomes) analyses to maximize statistical power and provide temporal ordering, respectively. We also conducted follow-up moderation (Lag × Stressful Event Intensity) analyses. We hypothesized that smokers would be more likely to report both smoking and craving as the intensity of stressful events increased. Cigarette smokers (N = 125; 77 male) were randomly assigned to take nicotine replacement therapy (NRT) or placebo and provided 4x daily self-reports during the first 2 weeks of a quit attempt. Stressful events increased craving and the probability of smoking in concurrent analyses, and lag moderated the effect of stressful event intensity in follow-up prospective lagged analyses. NRT reduced the probability of smoking but not craving and did not moderate the effect of stressful events on smoking or craving. This study supports a prospective relationship between stressful events and smoking/craving in situ and demonstrates that NRT does not reduce the impact of stressors on smoking or craving. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prospective Prediction of Lapses in Opioid Use Disorder: Protocol for a Personal Sensing Study.

BACKGROUND: Successful long-term recovery from opioid use disorder (OUD) requires continuous lapse risk monitoring and appropriate use and adaptation of recovery-supportive behaviors as lapse risk changes. Available treatments often fail to support long-term recovery by failing to account for the dynamic nature of long-term recovery. OBJECTIVE: The aim of this protocol paper is to describe research that aims to develop a highly contextualized lapse risk prediction model that forecasts the ongoing probability of lapse. METHODS: The participants will include 480 US adults in their first year of recovery from OUD. Participants will report lapses and provide data relevant to lapse risk for a year with a digital therapeutic smartphone app through both self-report and passive personal sensing methods (eg, cellular communications and geolocation). The lapse risk prediction model will be developed using contemporary rigorous machine learning methods that optimize prediction in new data. RESULTS: The National Institute of Drug Abuse funded this project (R01DA047315) on July 18, 2019 with a funding period from August 1, 2019 to June 30, 2024. The University of Wisconsin-Madison Health Sciences Institutional Review Board approved this project on July 9, 2019. Pilot enrollment began on April 16, 2021. Full enrollment began in September 2021. CONCLUSIONS: The model that will be developed in this project could support long-term recovery from OUD-for example, by enabling just-in-time interventions within digital therapeutics. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29563.

Stress Allostasis in Substance Use Disorders: Promise, Progress, and Emerging Priorities in Clinical Research.

Clinicians and researchers alike have long believed that stressors play a pivotal etiologic role in risk, maintenance, and/or relapse of alcohol and other substance use disorders (SUDs). Numerous seminal and contemporary theories on SUD etiology posit that stressors may motivate drug use and that individuals who use drugs chronically may display altered responses to stressors. We use foundational basic stress biology research as a lens through which to evaluate critically the available evidence to support these key stress-SUD theses in humans. Additionally, we examine the field's success to date in targeting stressors and stress allostasis in treatments for SUDs. We conclude with our recommendations for how best to advance our understanding of the relationship between stressors and drug use, and we discuss clinical implications for treatment development.

Acute prazosin administration does not reduce stressor reactivity in healthy adults.

RATIONALE: Norepinephrine plays a critical role in the stress response. Clarifying the psychopharmacological effects of norepinephrine manipulation on stress reactivity in humans has important implications for basic neuroscience and treatment of stress-related psychiatric disorders, such as posttraumatic stress disorder and alcohol use disorders. Preclinical research implicates the norepinephrine alpha-1 receptor in responses to stressors. The No Shock, Predictable Shock, Unpredictable Shock (NPU) task is a human laboratory paradigm that is well positioned to test cross-species neurobiological stress mechanisms and advance experimental therapeutic approaches to clinical trials testing novel treatments for psychiatric disorders. OBJECTIVES: We hypothesized that acute administration of prazosin, a noradrenergic alpha-1 antagonist, would have a larger effect on reducing stress reactivity during unpredictable, compared to predictable, stressors in the NPU task. METHODS: We conducted a double-blind, placebo-controlled, crossover randomized controlled trial in which 64 healthy adults (32 female) completed the NPU task at two visits (2 mg prazosin vs. placebo). RESULTS: A single acute dose of 2 mg prazosin did not reduce stress reactivity in a healthy adult sample. Neither NPU startle potentiation nor self-reported anxiety was reduced by prazosin (vs. placebo) during unpredictable (vs. predictable) stressors. CONCLUSIONS: Further research is needed to determine whether this failure to translate preclinical neuroscience to human laboratory models is due to methodological factors (e.g., acute vs. chronic drug administration, brain penetration, study population) and/or suggests limited clinical utility of noradrenergic alpha-1 antagonists for treating stress-related psychiatric disorders.

Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

RATIONALE: Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. OBJECTIVES: The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. METHODS: Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. RESULTS: Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. CONCLUSIONS: These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

The effects of social contact on cocaine intake in female rats.

BACKGROUND: Studies conducted in male rats report that social contact can either facilitate or inhibit drug intake depending on the behavior of social partners. The purpose of the present study was to: (1) examine the effects of social contact on cocaine intake in female rats, (2) examine the behavioral mechanisms by which social contact influences cocaine intake, and (3) examine whether the estrous cycle moderates the effects of social contact on cocaine intake. METHODS: Female rats were assigned to either isolated or pair-housed conditions in which a social partner either had access to cocaine (cocaine partner) or did not have access to cocaine (abstinent partner). Pair-housed rats were tested in custom-built operant conditioning chambers that allowed both rats to be tested simultaneously in the same chamber. RESULTS: Rats housed with a cocaine partner self-administered more cocaine than isolated rats and rats housed with an abstinent partner. A behavioral economic analysis indicated that these differences were driven by a greater intensity of cocaine demand (i.e., greater intake at lower unit prices) in rats housed with a cocaine partner. Multivariate modeling revealed that the estrous cycle did not moderate the effects of social contact on cocaine intake. CONCLUSIONS: These findings indicate that: (1) social contact influences cocaine self-administration in females in a manner similar to that reported in males, (2) these effects are due to differences in the effects of social contact on the intensity of cocaine demand, and (3) these effects are consistent across all phases of the estrous cycle.

Acute bouts of wheel running decrease cocaine self-administration: Influence of exercise output.

Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration. Female rats were trained to run in automated running wheels, implanted with intravenous catheters, and allowed to self-administer cocaine on a fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test session, subjects engaged in acute bouts of exercise in which they ran for 0, 30, or 60min at 12m/min. Acute bouts of exercise before test sessions decreased cocaine self-administration in an output-dependent manner, with the greatest reduction in cocaine intake observed in the 60-min exercise condition. Exercise did not reduce cocaine self-administration when wheel running and test sessions were separated by 12h, and exercise did not reduce responding maintained by food or responding during a saline substitution test. These data indicate that acute bouts of exercise decrease cocaine self-administration in a time- and output-dependent manner. These results also add to a growing body of literature suggesting that physical activity may be an effective component of drug abuse treatment programs.