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Cigarette smoking and smoking cessation are associated with changes in cognition and DNA methylation; however, the neurobiological correlates of these effects have not been fully elucidated, especially in long-term cessation. Cognitive performance, percent methylation of the aryl hydrocarbon receptor repressor ( AHRR ) gene, and abstinence duration were used as references to supervise a multimodal fusion analysis of functional, structural, and diffusion magnetic resonance imaging (MRI) data, in order to identify associated brain networks in smokers and ex-smokers. Correlations among these networks and with smoking-related measures were performed. Cognition-, methylation-, and abstinence duration-associated networks discriminated between smokers and ex-smokers and correlated with differences in fractional amplitude of low frequency fluctuations (fALFF) values, gray matter volume (GMV), and fractional anisotropy (FA) values. Long-term smoking cessation was associated with more accurate cognitive performance, as well as lower fALFF and more GMV in the hippocampus complex. The methylation- and abstinence duration-associated networks positively correlated with smoking-related measures of abstinence duration and percent methylation, respectively, suggesting they are complementary measures. This analysis revealed structural and functional co-alterations linked to smoking abstinence and cognitive performance in brain regions including the insula, frontal gyri, and lingual gyri. Furthermore, AHRR methylation, a promising epigenetic biomarker of smoking recency, may provide an important complement to self-reported abstinence duration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qi, Fu, Wu, Calhoun, Zhang, Daughters, Hsu, Jiang, Vergara, Sui and Addicott.)

Only a small minority of people with substance use disorders (SUDs) receive treatment. A focus on abstinence is pervasive in SUD treatment, defining success in both research and practice, and punitive measures are often imposed on those who do not abstain. Most adults with SUD do not seek treatment because they do not wish to stop using substances, though many also recognize a need for help. This narrative review considers the need for increased research attention on nonabstinence psychosocial treatment of SUD - especially drug use disorders - as a potential way to engage and retain more people in treatment, to engage people in treatment earlier, and to improve treatment effectiveness. We describe the development of nonabstinence approaches within the historical context of SUD treatment in the United States, review theoretical and empirical rationales for nonabstinence SUD treatment, and review existing models of nonabstinence psychosocial treatment for SUD among adults to identify gaps in the literature and directions for future research. Despite significant empirical support for nonabstinence alcohol interventions, there is a clear gap in research examining nonabstinence psychosocial treatment for drug use disorders. Future research must test the effectiveness of nonabstinence treatments for drug use and address barriers to implementation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There is a need for parsimonious behavioral interventions to support HIV and substance use treatment outcomes for low-income, Black/African American individuals living with HIV. This randomized clinical trial (N = 61) evaluated Act Healthy (AH), an integrated behavioral intervention to reduce substance use and improve medication adherence, compared to supportive counseling (SC) plus Life-Steps medication adherence counseling on substance use, craving, adherence-related outcomes, and depression over one year. Participants in AH had significantly steeper decreases in cravings compared to SC, but no significant differences in substance use. Across both groups, there was a significant increase in probability of being on antiretroviral therapy (ART) (86% on ART at 12 months vs. 56% at baseline), and a significant decrease in medication nonadherence. Findings provide preliminary support for an intervention to reduce cravings and strategies to improve ART use in a hard-to-reach, vulnerable population at high risk for poor treatment outcomes and ongoing HIV transmission. TRIAL REGISTRATION: ClinicalTrials.gov trial registration number: identifier: NCT01351454. Retrospectively registered on May 10, 2011., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Deficits in the ability to experience reward from natural, substance-free activities and stimuli is a common mechanism contributing to both opiate use disorder and depressive symptoms, and is a target of behavioral-focused treatments for substance use and depression. Although the neural response to monetary, positive affect-eliciting and social images has been investigated, the neural response to images representing substance-free activity engagement remains untested. The current study tested the neural response to anticipation and receipt of substance-free activity engagement images and monetary reward in opiate use disorder patients with elevated depressive symptoms compared to healthy controls., Methods: Sixteen male opiate use disorder detoxification patients with elevated depressive symptoms (Beck Depression Inventory (BDI-II) ≥ 14) (OUDD M age  = 32.19 years, SD = 8.17 years) and seventeen male healthy controls (BDI-II < 14) (HC: M age  = 26.82 years, SD = 5.29 years) completed the Monetary Incentive Delay (MID) and newly developed Activity Incentive Delay (AID) tasks. Within- and between-group whole-brain contrasts tested activation during anticipation ([reward]-[non-reward]) and receipt ([win]-[non-win]) of substance-free activity image, monetary, and substance-free activity relative to monetary (AID-MID), reward., Results: OUDD demonstrated significantly lower activation in reward regions during anticipation and significantly greater activation during receipt of substance-free activity image reward compared to HC. OUDD demonstrated significantly lower activation during anticipation of substance-free activity reward relative to monetary reward, compared to HC., Conclusions: The observed reduction in frontostriatal response to reward anticipation of substance-free activity engagement images in OUDD, yet increased neural response to reward receipt, supports theory linking reductions in reward processing with deficits in motivation for substance-free activity engagement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Research examining directionality of the relationship between depressive symptoms and substance use following treatment entry is limited. Furthermore, substances differ in their neurobiological effects on mood. The relationship between depression and substance use following treatment entry may be moderated by dependence on specific substances. The study tested (a) lagged effects between depressive symptoms and substance use frequency following substance use treatment entry through a 1-year post-treatment follow-up and (b) if substance dependence type moderates these effects., Methods: Participants (N = 263) entering residential treatment were assessed for DSM-IV substance dependence, depressive symptoms (Beck Depression Inventory), and percentage of substance use days at post-treatment, 1-, 3-, 6- and 12-month follow-up assessments (time t 0 to t 4 ). Linear mixed effects models tested lagged effects between depressive symptoms and substance use frequency and the impact of substance type (i.e., dependence on alcohol, cannabis, opioid, cocaine, hallucinogen/PCP) on this relationship., Results: After controlling for concurrent effects, substance type moderated each longitudinal relationship. Depressive symptoms significantly predicted substance use frequency at the subsequent follow-up assessment, only among individuals with pre-treatment opioid dependence (B = 5.55, SE = 0.89, z = 6.21, p < 0.01). Substance use frequency significantly predicted depressive symptoms at the subsequent follow-up assessment, but not among individuals with cannabis dependence at pre-treatment (B = 1.01, SE = 0.22, t (524) = 4.49, p < 0.01)., Conclusions: The directionality of depression-substance use comorbidity may differ based on the substance of dependence at pre-treatment. Opioid users may especially benefit from treating both depression and substance use., (Copyright © 2019. Published by Elsevier B.V.)

Distress tolerance is the capacity to withstand negative affective states in pursuit of a goal. Low distress tolerance may bias an individual to avoid or escape experiences that induce affective distress, but the neural mechanisms underlying the bottom-up generation of distress and its relationship to behavioral avoidance are poorly understood. During a neuroimaging scan, healthy participants completed a mental arithmetic task with easy and distress phases, which differed in cognitive demands and positive versus negative auditory feedback. Then, participants were given the opportunity to continue playing the distress phase for a financial bonus and were allowed to quit at any time. The persistence duration was the measure of distress tolerance. The easy and distress phases activated auditory cortices and fronto-parietal regions. A task-based functional connectivity analysis using the left secondary auditory cortex (i.e., planum temporale) as the seed region revealed stronger connectivity to fronto-parietal regions and anterior insula during the distress phase. The distress-related connectivity between the seed region and the left anterior insula was negatively correlated with distress tolerance. The results provide initial evidence of the role of the anterior insula as a mediating link between the bottom-up generation of affective distress and top-down behavioral avoidance of distress., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To compare outcomes for a behavioral activation group treatment for substance use [life enhancement treatment for substance use (LETS ACT)] versus a time and group size-matched control condition delivered in a residential treatment setting., Design: Single-site two-arm parallel-group randomized clinical trial with follow-up assessment at 3, 6 and 12 months post-treatment., Setting: Residential substance use treatment facility in the United States., Participants: Participants were 263 adults [mean age 42.7 (11.8); 29.5% female; 95.4% African American; 73.2% court mandated] whose insurance dictated 30-day (65.9%) or 90-day (34.1%) treatment duration., Intervention and Comparator: LETS ACT (n = 142) is a treatment developed originally for depression and modified for substance use. It teaches participants to increase positively reinforcing value-driven activities in order to counter depression and relapse. The control group [supportive counseling (SC); n = 121] received time and group size-matched supportive counseling. Treatment was delivered in five or eight 1-hour sessions depending on patient length of stay., Measurements: Percentage abstinent at follow-up, percentage of substance use days among those reporting use, depressive symptoms [Beck Depression Inventory (BDI)] and adverse consequences of drug use [Short Inventory of Problems-Alcohol and Drug (SIP-AD)]., Findings: LETS ACT had significantly higher abstinence rates at 3 months [odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.3-3.7], 6 months (OR = 2.6, 95% CI= 1.3-5.0) and 12 months (OR = 2.9, 95% CI = 1.3-6.1) post-treatment compared with SC. LETS ACT participants reported significantly fewer adverse consequences from substance use at 12 months post-treatment [B = 4.50, standard error (SE) = 2.17, 95% CI = 0.22-8.78]. Treatment condition had no effect on percentage substance use days among those who resumed use or on change in depressive symptoms; the latter decreased over time only in those who remained abstinent after residential treatment irrespective of condition (B = 0.43, SE = 0.11, 95% confidence interval = 0.22-0.65)., Conclusions: A behavioral activation group treatment for substance use (LETS ACT) appears to increase the likelihood of abstinence and reduce adverse consequences from substance use up to 12 months post-treatment., (© 2017 Society for the Study of Addiction.)

Distress tolerance (DT), defined as the ability to persist in goal-directed behavior while experiencing psychological distress, is associated with greater frequency of substance use and poor treatment outcomes. To examine a potential causal role substance use may play in DT, we developed a rodent model of DT in which rats had to press a lever within a continuously decreasing time window for reward while receiving negative feedback on failure trials. DT was defined as the time rats continued to seek reward before quitting the task. We assessed the relationship of DT with cocaine seeking/taking by measuring DT before cocaine self-administration (SA), and after 1 week and 1 month of drug abstinence. We found that DT prior to cocaine SA did not predict cocaine seeking/taking, yet DT measured after 1 month abstinence significantly predicted subsequent high levels of early session cocaine taking. Additionally, high DT measured after abstinence protected against high cocaine seeking, but this protective effect was blocked in rats with high impulsivity. Finally, while a decrease in 1 month-abstinent DT was observed following SA across treatment conditions, among cocaine-exposed rats, greater cocaine SA correlated with a steeper decrease in DT. These results show that low DT after drug abstinence is associated with heightened levels of cocaine seeking and taking behavior and that impulsivity influences this effect. Collectively, these results support the validity of our rodent DT model while extending the human literature and set the foundation for future animal studies designed to determine neural mechanisms underlying DT., (© 2017 Society for the Study of Addiction.)

Background: An estimated 40% to 70% of individuals treated for a substance use disorder relapse within one year following treatment (Walitzer and Dearing, 2006). Relapse is often driven by the need to cope with intense negative affect (Koob, 2013). Emotion differentiation, defined as the ability to distinguish among various emotion states, has been linked to better behavioral control in the face of negative affect (Kashdan et al., 2015). The aim of the current study was to determine if higher levels of emotion differentiation are associated with the risk of experiencing an initial lapse following entry into residential substance use treatment., Methods: A total of 213 substance users (69.5% male, 94.4% African American, M age=43.01±11.35years) entering residential treatment were assessed on study variables at pre- and post-treatment, and at 1-, 3-, 6- and 12-month post-treatment. Emotion differentiation was calculated using ratings on five negative affect items derived from the Positive and Negative Affect Schedule (PANAS; Watson et al., 1988) at five assessment points., Results: A Cox proportional-hazards regression model adjusting for age and negative affect intensity demonstrates that for every unit increase in emotion differentiation, there is a 27% reduction in the likelihood of initial lapse on any given day (OR=0.73; 95% CIs [0.56, 0.95])., Conclusions: The ability to differentiate among negative emotion states protects against initial lapse following treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Our understanding of the conditions that influence substance abuse treatment retention in urban African American substance users is limited. This study examined the interacting effect of circumstances, motivation, and readiness (CMR) with distress tolerance to predict substance abuse treatment retention in a sample of urban African American treatment-seeking substance users., Methods: Data were collected from 81 African American substance users entering residential substance abuse treatment facility in an urban setting. Participants completed self-reported measures on CMR and distress tolerance. In addition, participants were assessed on psychiatric comorbidities, substance use severity, number of previous treatments, and demographic characteristics. Data on substance abuse treatment retention were obtained using administrative records of the treatment center., Results: Logistic regression analysis found that the interaction of CMR and distress tolerance was significant in predicting substance abuse treatment retention. Higher score on CMR was significantly associated with increased likelihood of treatment retention in substance users with higher distress tolerance, but not in substance users with lower distress tolerance., Conclusions: Findings of the study indicate that at higher level of distress tolerance, favorable external circumstances, higher internal motivation, and greater readiness to treatment are important indicators of substance abuse treatment retention. The study highlights the need for assessing CMR and distress tolerance levels among substance users entering treatment, and providing targeted interventions to increase substance abuse treatment retention and subsequent recovery from substance abuse among urban African American substance users., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Research indicates that increased risk-taking propensity (RTP) is associated with higher alcohol use. There is also some evidence to suggest that it is not just a state factor or 'scar,' but instead a vulnerability factor. If this is the case, increased RTP should be evident in healthy individuals that are at risk for alcohol use. To date, few studies have examined whether RTP is a familial vulnerability factor and thus, the aim of the current study was to test whether RTP aggregates within families and if increased RTP is evident in biological family members at risk for alcohol use. Sample 1 included 87 biological, adult sibling pairs and Sample 2 included 111 biological mother and adolescent dyads (total N = 396). All participants completed a behavioral measure of RTP and were assessed for alcohol use. Results in both samples were strikingly consistent. In Sample 1, RTP was correlated among siblings and greater frequency of proband alcohol use predicted greater sibling RTP, over and above sibling alcohol use. In Sample 2, RTP was correlated among mothers and their offspring and greater maternal alcohol use problems predicted greater adolescent RTP over and above adolescent substance use. Together, these findings suggest that RTP may be a familial vulnerability factor for alcohol use as it aggregates within families and is increased in relatives of individuals with higher levels of alcohol use., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Depression is associated with substance use problems; however, the specific individual characteristics influencing this association are not well identified. Empirical evidence and theory suggest that gender and distress tolerance-defined behaviorally as an individual's ability to persist in goal-directed behavior while experiencing negative affective states-are important underlying factors in this relationship. Hence, the purpose of the current study was to examine whether gender and distress tolerance moderate the relationship between depressive symptoms and substance use problems., Methods: Participants included 189 substance users recruited from a residential substance abuse treatment center. The Short Inventory of Problems-Alcohol and Drugs scale was used to measure self-reported substance use problems. The Beck Depression Inventory was used to assess self-reported depressive symptoms. Gender was self-reported, and distress tolerance was behaviorally indexed by the Computerized Paced Auditory Serial Addition Task., Results: Hierarchical linear regression analysis indicated a significant three-way interaction of depressive symptoms, gender, and distress tolerance on substance use problems, adjusting for relevant demographic variables, anxiety symptoms, impulsivity, as well as DSM-IV psychiatric disorders. Probing of this three-way interaction demonstrated a significant positive association between depressive symptoms and substance use problems among females with low distress tolerance., Conclusion: Findings indicate that female treatment-seeking substance users with high levels of depressive symptoms exhibit greater substance use problems if they also evidence low distress tolerance. Study implications are discussed, including the development of prevention and intervention programs that target distress tolerance skills., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Impaired tolerance to distress may help explain part of the cognitive and functional impairments in schizophrenia (SZ). This project investigated distress intolerance in SZ patients as compared to controls, and whether distress intolerance represented an independent domain in relationship to symptoms, cognition, and functional capacity. Healthy controls (n=43) and SZ (n=65) completed a psychological distress challenge experiment and their levels of intolerance to distress were estimated. SZ showed increased distress intolerance such that they were significantly more likely to terminate the distress challenge session early compared to controls. Greater distress intolerance was associated with reduced functional capacity and worse cognitive performance in SZ. Mediation analyses suggested that distress intolerance had an independent effect on functional capacity, while some of this effect was mediated by cognitive performance. Our results suggest that distress intolerance is a promising domain for treatment research, and functional capacity may be improved by targeting treatments towards SZ patient׳s ability to tolerate distress., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Antiretroviral therapy to treat HIV/AIDS has substantially improved clinical outcomes among patients living with HIV/AIDS, but only in the presence of very consistent adherence. One of the most prevalent and impactful individual-level predictors of poor adherence is depressive symptoms, even at subthreshold levels. Evidence-based cognitive behavioral interventions exist to address improvements in depressive symptoms and adherence in this population, yet these techniques have largely been designed and tested as individual treatments for delivery in mental health settings. This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits) and few hands-on resources exist to guide this process. As such, primary aims of this study were to adapt and implement evidence-based cognitive behavioral techniques for depression (behavioral activation; BA) and HIV medication adherence (Life-Steps) that have potential for dissemination in an outpatient community health center. The intervention incorporated feedback from health center staff and utilized a modular, group format that did not rely on sequential session attendance. Feasibility was examined over 8 weeks ( n = 13). Preliminary effects on depression, health-related quality of life, and medication adherence were examined and exit interviews were conducted with a subset of participants ( n = 4) to inform future modifications. Treatment descriptions and recommendations for effective clinical implementation based on patient and clinician feedback are provided along with case material of two individual patients and an example group session. Current efforts are an important next step for disseminating evidence-based techniques for depression and HIV medication adherence to community health center or AIDS service organization settings.

Distress tolerance (DT) is an established construct contributing to the onset and maintenance of psychopathology in adulthood; however, few studies have examined the role of DT in older adolescent psychopathology. Emerging data suggest that gender and race may influence this relation. Therefore, the current study examined the relation between gender, race, and DT on parent-reported internalizing and externalizing DSM-oriented symptoms among a community sample of 128, 14-18 year old adolescents. Results indicated a moderating effect of gender on affective problems, such that females with low DT, but not males, displayed significantly greater affective problems. Findings also indicated a significant moderating effect of race, such that Caucasians with low DT, but not African Americans, displayed significantly higher somatic, oppositional defiant, and conduct problems. These findings suggest that DT is an important clinical variable in older adolescence, particularly among Caucasians and females., (Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

The two most common comorbid conditions with HIV are substance use disorders and depression, and individuals with comorbid HIV, depression, and substance dependence face a more chronic and treatment-resistant course. As an example of how to adapt evidence-based approaches to a complex comorbid population, the current case study examined the integration of a combined depression and HIV medication adherence treatment. The resulting intervention, ACT HEALTHY, combines a brief behavioral activation approach specifically developed to treat depression in individuals receiving residential substance abuse treatment (LETS ACT; Daughters et al., 2008) with a brief cognitive-behavioral approach to improving HIV medication adherence (Life-Steps; Safren et al., 1999; Safren et al., 2009). The current case series demonstrates the use of ACT HEALTHY among 3 depressed HIV-positive, low-income African Americans entering residential substance abuse treatment.

The current study aimed to develop a measure for assessing the various motivations for sexual risk behavior (SRB) across commercial (involving the exchange of sex for money or drugs) and casual (nonregular) partners in a sample of inner-city, primarily African American drug users, and to examine the relationship of these motivations with a history of childhood trauma, as well as current symptoms of depression, posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). Exploratory factor analysis indicated a 5-factor solution for commercial partner type, and a 4-factor solution for casual partner type, including the motivations of sexual sensation-seeking, intimacy seeking, reassurance-seeking, emotional avoidance, and emotional expressivity. Emotional avoidance and emotional expressivity were strongly related to childhood trauma and PTSD and BPD symptoms. These results provide initial results for mechanisms underlying the relationship between SRB and a history of trauma and psychopathology.