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Objective: The authors examined the initial implementation of the Indiana Adolescent Addiction Access (AAA) program, modeled on the widely disseminated Child Psychiatry Access Program framework. The AAA program developed a statewide consultation helpline to connect health care providers with adolescent addiction specialists., Methods: The AAA line was staffed by a coordinator, who fielded initial questions, and on-call clinical specialists (social workers, nurse practitioners, psychiatrists, and psychologists), who were paged to complete telephone consultations and provide care recommendations. When necessary, AAA providers offered urgent clinical assessments and initiated treatment. Descriptive analyses were performed for key variables over the first 21 months of AAA operations., Results: From July 2021 to March 2023, a total of 125 consultations were completed. Most callers were health care providers (71%) or parents (27%). Calls pertained to youths ages 10-18 years (mean±SD age=16.4±1.3; 62% of callers were male, 84% White, and 11% Black), with concerns around cannabis (63%), opioids (38%), and other substances. About 26% of calls related to an overdose, and 41% of cases were rated as severe. Recommendations included starting new medications (17%) or outpatient therapy (86%), and 17% of consultations resulted in urgent evaluations., Conclusions: The Indiana AAA program helps overcome key barriers to adolescent substance use treatment. Increasing the capacity to initiate medication for opioid use disorder and other treatment rapidly through consultation and direct care is a promising, scalable approach for preventing overdose deaths among youths., Competing Interests: The authors report no financial relationships with commercial interests.

Importance: Prescribing medications for opioid use disorders (MOUD), including buprenorphine, naltrexone, and methadone, to adolescents remains an underused evidence-based strategy for reducing harms associated with opioid use., Objective: To identify potential associations between clinician- and community-level characteristics regarding clinicians' self-reported willingness to prescribe MOUD to adolescents., Design, Setting, and Participants: This cross-sectional study included a phone survey of Indiana clinicians and spatial analysis of community-level characteristics. Clinicians were eligible for inclusion in analyses if actively providing health care and listed on the Buprenorphine Practitioner Locator website, a publicly available national registry of clinicians possessing a waiver to legally prescribe buprenorphine (ie, waivered clinicians)., Exposures: Community-level characteristics, including total population, rurality or urbanicity, percentage with incomes below the federal poverty line, and racial or ethnic makeup., Main Outcomes and Measures: Clinicians were asked about their willingness to prescribe MOUD to adolescents younger than 18 years if clinically indicated. Responses were recorded as no, yes, or yes with conditions., Results: Among the 871 clinicians listed on the website as of July 2022, 832 were eligible for inclusion and contacted by phone. Among waivered clinicians, 759 (91.2%) reported being unwilling to prescribe MOUD to adolescents, 73 clinicians (8.8%) reported willingness to prescribe MOUD to adolescents, and only 24 (2.9%) would do so without conditions. A multivariable logistic regression model including spatially lagged community-level variables showed that, among areas with waivered clinicians, clinicians practicing in more populated areas were significantly less likely to prescribe to adolescents (β = 0.65; 95% CI, 0.49-0.87; P = .003). Similarly, those in more rural areas were significantly more likely to prescribe to adolescents (β = 1.27; 95% CI, 1.02-1.58; P = .03). Variation in clinician willingness to prescribe was not explained by other community-level characteristics. Among all waivered clinicians, advanced practice clinicians were less likely than physicians to report willingness to prescribe (β = 0.58; 95% CI, 0.35-0.97; P = .04), as were physicians without any specialty training relevant to MOUD prescribing when compared with family medicine clinicians (β = 0.40; 95% CI, 0.18-0.89; P = .03). A small subgroup of waivered clinicians had training in pediatrics (13 clinicians [1.6%]), and none were willing to prescribe MOUD to adolescents., Conclusions and Relevance: From this cross-sectional study, it appears that Indiana adolescents continued to face gaps in access to MOUD treatment, despite its well-established efficacy. Programs that support primary care practitioners, including family medicine clinicians and pediatricians, in safe and appropriate use of MOUD in adolescents may bridge these gaps.

Background: Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth., Methods: Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training)., Results: Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD., Conclusions: These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally., (© 2024. The Author(s).)

Introduction: Rates of substance use are high among youth involved in the legal system (YILS); however, YILS are less likely to initiate and complete substance use treatment compared to their non legally-involved peers. There are multiple steps involved in connecting youth to needed services, from screening and referral within the juvenile legal system to treatment initiation and completion within the behavioral health system. Understanding potential gaps in the care continuum requires data and decision-making from these two systems. The current study reports on the development of data dashboards that integrate these systems' data to help guide decisions to improve substance use screening and treatment for YILS, focusing on end-user feedback regarding dashboard utility., Methods: Three focus groups were conducted with n = 21 end-users from juvenile legal systems and community mental health centers in front-line positions and in decision-making roles across 8 counties to gather feedback on an early version of the data dashboards; dashboards were then modified based on feedback., Results: Qualitative analysis revealed topics related to (1) important aesthetic features of the dashboard, (2) user features such as filtering options and benchmarking to compare local data with other counties, and (3) the centrality of consistent terminology for data dashboard elements. Results also revealed the use of dashboards to facilitate collaboration between legal and behavioral health systems., Conclusions: Feedback from end-users highlight important design elements and dashboard utility as well as the challenges of working with cross-system and cross-jurisdiction data., (© 2024. The Author(s).)

Purpose: Computerized adaptive tests (CATs) are highly efficient assessment tools that couple low patient and clinician time burden with high diagnostic accuracy. A CAT for substance use disorders (CAT-SUD-E) has been validated in adult populations but has yet to be tested in adolescents. The purpose of this study was to perform initial evaluation of the K-CAT-SUD-E (i.e., Kiddy-CAT-SUD-E) in an adolescent sample compared to a gold-standard diagnostic interview., Methods: Adolescents ( N  = 156; aged 11-17) with diverse substance use histories completed the K-CAT-SUD-E electronically and the substance related disorders portion of a clinician-conducted diagnostic interview (K-SADS) via tele-videoconferencing platform. The K-CAT-SUD-E assessed both current and lifetime overall SUD and substance-specific diagnoses for nine substance classes., Results: Using the K-CAT-SUD-E continuous severity score and diagnoses to predict the presence of any K-SADS SUD diagnosis, the classification accuracy ranged from excellent for current SUD (AUC = 0.89, 95% CI = 0.81, 0.95) to outstanding (AUC = 0.93, 95% CI = 0.82, 0.97) for lifetime SUD. Regarding current substance-specific diagnoses, the classification accuracy was excellent for alcohol (AUC = 0.82), cannabis (AUC = 0.83) and nicotine/tobacco (AUC = 0.90). For lifetime substance-specific diagnoses, the classification accuracy ranged from excellent (e.g., opioids, AUC = 0.84) to outstanding (e.g., stimulants, AUC = 0.96). K-CAT-SUD-E median completion time was 4 min 22 s compared to 45 min for the K-SADS., Conclusions: This study provides initial support for the K-CAT-SUD-E as a feasible accurate diagnostic tool for assessing SUDs in adolescents. Future studies should further validate the K-CAT-SUD-E in a larger sample of adolescents and examine its acceptability, feasibility, and scalability in youth-serving settings.

This review summarizes treatments for cannabis use disorder (CUD) in adolescents. The best supported CUD treatments are cognitive behavioral psychotherapies, including family-based models that facilitate environmental changes and youth-focused models that incorporate skills training, motivational interviewing, and contingency management to promote reductions in cannabis use. Some medications show promise in reducing cannabis craving and withdrawal symptoms. Further research is needed on the efficacy and implementation of existing treatments given the changes in cannabis use trends over time and on emerging technologies that may expand access to evidence-based CUD treatments., Competing Interests: Disclosure The authors have nothing to disclose. Acknowledgement The authors wish to acknowledge support from NIH grant K12DA000357 (JH) and SAMHSA grant H79TI083595 (ZWA, LAH)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Youth with traumatic injury experience elevated risk for behavioral health disorders, yet posthospital monitoring of patients' behavioral health is rare. The Telehealth Resilience and Recovery Program (TRRP), a technology-facilitated and stepped access-to-care program initiated in hospitals and designed to be integrated seamlessly into trauma center operations, is a program that can potentially address this treatment gap. However, the TRRP was originally developed to address this gap for mental health recovery but not substance use. Given the high rates of substance and opioid use disorders among youth with traumatic injury, there is a need to monitor substance use and related symptoms alongside other mental health concerns., Objective: This study aimed to use an iterative, user-guided approach to inform substance use adaptations to TRRP content and procedures., Methods: We conducted individual semistructured interviews with adolescents (aged 12-17 years) and young adults (aged 18-25 years) who were recently discharged from trauma centers (n=20) and health care providers from two level 1 trauma centers (n=15). Interviews inquired about reactions to and recommendations for expanding TRRP content, features, and functionality; factors related to TRRP implementation and acceptability; and current strategies for monitoring patients' postinjury physical and emotional recovery and opioid and substance use. Interview responses were transcribed and analyzed using thematic analysis to guide new TRRP substance use content and procedures., Results: Themes identified in interviews included gaps in care, task automation, user personalization, privacy concerns, and in-person preferences. Based on these results, a multimedia, web-based mobile education app was developed that included 8 discrete interactive education modules and 6 videos on opioid use disorder, and TRRP procedures were adapted to target opioid and other substance use disorder risk. Substance use adaptations included the development of a set of SMS text messaging-delivered questions that monitor both mental health symptoms and substance use and related symptoms (eg, pain and sleep) and the identification of validated mental health and substance use screening tools to monitor patients' behavioral health in the months after discharge., Conclusions: Patients and health care providers found the TRRP and its expansion to address substance use acceptable. This iterative, user-guided approach yielded novel content and procedures that will be evaluated in a future trial., (©Zachary W Adams, Brigid R Marriott, Swathi Karra, Elizabeth Linhart-Musikant, Jodi L Raymond, Lydia J Fischer, Kristina A Bixler, Teresa M Bell, Eric A Bryan, Leslie A Hulvershorn. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.11.2023.)

Although cannabis is a naturally occurring plant with a long history of use by humans, the chemicals it contains, called cannabinoids, can act on the human body in many ways. Use of cannabis during important periods of development, such as during pregnancy and adolescence, can have a long-lasting impact on the way the brain forms and develops its systems to control emotions and other functions. This article gives an overview of some of the effects of cannabinoids on the developing brain, before birth and as teenagers, and provides information about how young people can prevent or minimize the negative effects of cannabis on their brains., Competing Interests: CONFLICT OF INTEREST: KG has provided consultation to Jazz Pharmaceuticals. The remaining 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.

A significant gap remains in the availability and accessibility of evidence-based treatments (EBTs) in community substance use disorder (SUD) treatment. This study describes a 2-year statewide training initiative that sought to address this gap by training community-based therapists in motivational enhancement/cognitive behavioral therapy (MET/CBT). Therapists (N = 93) participated in a 2-day MET/CBT workshop followed by bi-weekly clinical consultation, fidelity monitoring, guided readings, and online resources. Therapists completed pre-training and follow-up assessments measuring knowledge, attitudes, confidence, and implementation barriers. Most therapists attended 10 or more consultation calls. Submission of session recordings for feedback was the least utilized training element. Therapists reported increased confidence in their ability to implement MET/CBT for SUD and demonstrated improvement in MI and CBT knowledge. Therapists reported several implementation barriers, including lack of time and opportunity to treat patients with MET/CBT. Recommendations for future training initiatives and addressing the barriers identified in this study are discussed., (© 2023. National Council for Mental Wellbeing.)

Background: Risky decision-making is associated with the development of substance use behaviors during adolescence. Although prior work has investigated risky decision-making in adolescents at familial high risk for developing substance use disorders (SUDs), little research has controlled for the presence of co-morbid externalizing disorders (EDs). Additionally, few studies have investigated the role of parental impulsivity in offspring neurobiology associated with risky decision-making., Methods: One-hundred twenty-five children (28 healthy controls, 47 psychiatric controls with EDs without a familial history of SUD, and 50 high-risk children with co-morbid EDs with a familial history of SUD) participated in the Balloon Analog Risk Task while undergoing functional magnetic resonance imaging. Impulsivity for parents and children was measured using the UPPS-P Impulsive Behavior Scale., Results: We found that individuals in the psychiatric control group showed greater activation, as chances of balloon explosion increased, while making choices, relative to the healthy control and high-risk groups in the rostral anterior cingulate cortex (rACC) and lateral orbitofrontal cortex (lOFC). We also found a positive association between greater activation and parental impulsivity in these regions. However, within rACC, this relationship was moderated by group, such that there was a positive relationship between activation and parental impulsivity in the HC group, but an inverse relationship in the HR group., Conclusions: These findings suggest that there are key differences in the neurobiology underlying risky decision-making in individuals with EDs with and without a familial history of SUD. The current findings build on existing models of neurobiological factors influencing addiction risk by integrating parental factors. This work paves the way for more precise risk models in which to test preventive interventions., Competing Interests: JN is an investigator for Janssen. The remaining 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. MA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Aloi, Kwon, Hummer, Crum, Shah, Pratt, Aalsma, Finn, Nurnberger and Hulvershorn.)

Purpose: Age of first exposure to tackle football and head impact kinematics have been used to examine the effect of head impacts on mental health outcomes. These measures coupled with retrospective and cross-sectional designs have contributed to conflicting results. The purpose of this study was to identify the effect of one season of head impact exposure, age of first exposure to football, and psychological need satisfaction on acute mental health outcomes in adolescent football players., Methods: This prospective single-season cohort study used sensor-installed mouthguards to collect head impact exposure along with surveys to assess age of first exposure to football, psychological satisfaction, depressive symptoms, anxiety symptoms, and thriving from football players at four high schools (n = 91). Linear regression was used to test the association of head impact exposure, age of first exposure, and psychological satisfaction with acute mental health outcomes., Results: A total of 9,428 impacts were recorded with a mean of 102 ± 113 impacts/player. Cumulative head impact exposure and age of first exposure were not associated with acute mental health outcomes at postseason or change scores from preseason to postseason. Greater psychological satisfaction was associated with fewer depressive symptoms (β = -0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (β = -0.021, SE = 0.008, p = .010), and greater thriving scores (β = 0.278, SE = 0.040, p = < .001) at postseason., Discussion: This study does not support the premise that greater single-season head impact exposure or earlier age of first exposure to tackle football is associated with worse acute mental health indicators over the course of a single season in adolescent football players., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD., Methods: Offspring of a parent with BD (oBD; n  = 266) or no psychiatric disorders ( n  = 174), aged 12-21 at recruitment, participated in the US and Australia. Empirically-derived profiles of FE classified offspring by their perceived levels of familial cohesion, flexibility, and conflict. Offspring BD-PRS were derived from Psychiatric Genomics Consortium BD-GWAS. Lifetime DSM-IV bipolar disorders were derived from the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. We used a novel stepwise approach for latent class modeling with predictors and distal outcomes., Results: Fifty-two offspring were diagnosed with BD. For those with well-functioning FE (two-thirds of the sample), higher BD-PRS tracked positively with liability for BD. However, for those with high-conflict FEs, the relationship between BD-PRS and liability to BD was negative, with highest risk for BD observed with lower BD-PRS. In exploratory analyses, European-ancestry offspring with BD had elevated history of suicidal ideation in high-conflict FE compared to well-functioning-FE, and of suicide attempt with low-BD-PRS and high-conflict FE., Conclusions: The data suggest that the relationship of BD-PRS and offspring liability for BD differed between well-functioning versus high-conflict FE, potentially in line with a multifactorial liability threshold model and supporting future study of and interventions improving family dynamics., Competing Interests: John I. Nurnberger, MD, is an investigator for Janssen. Philip Mitchell has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for advisory board membership or lectures. The remaining authors have declared that they have no competing or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

As adolescent vaping reaches epidemic rates in the United States, it is imperative that pediatric clinicians have access to medical knowledge on best practices for screening, assessing, and treating vaping-related substance use. The Teen Vaping ECHO (Extension for Community Healthcare Outcomes) program was developed to offer practical learning sessions focused on clinical management of adolescent vaping. This study describes the development, implementation, and evaluation of the program's impact on participants' knowledge, attitudes, and practices regarding treatment of adolescent vaping from registration to the end of the series. Participants were generally knowledgeable about vaping at registration and reported significant increases in comfort talking with patients about vaping, counseling patients on nicotine replacement products, and frequency of implementing best-practice screening strategies at the end of the series. This study suggests ECHO programs focused on improving clinical management of adolescent vaping may increase accessibility of evidence-based care and reduce harms associated with vaping in youth.

Background: Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics., Methods: We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213)., Results: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples., Conclusions: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations., (© 2022 Association for Child and Adolescent Mental Health.)

Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10 -7 ) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction. Overall, BD-PRS appeared to broadly impact epigenetic processes, with 1,183 genes mapped to nominal DMPs (p < 0.05); these displayed convergence with genes previously associated with BD, schizophrenia, chronotype, and risk taking. We tested poly-methylomic epigenetic profiles derived from nominal DMPs in two independent samples (n = 54 and n = 82, respectively), and conducted an exploratory evaluation of the effects of family environment, indexing cohesion and flexibility. This study highlights an important interplay between heritable risk and epigenetic factors, which warrant further exploration., (© 2022. The Author(s).)

Introduction: The Computerized Adaptive Test for Substance Use Disorder (CAT-SUD), an adaptive test based on multidimensional item response theory, has been expanded to include 7 specific Diagnostic and Statistical Manual, 5th edition (DSM-5) defined SUDs. Initial testing of the new measure, the CAT-SUD expanded (CAT-SUD-E) is reported here., Methods: 275 Community-dwelling adults (ages 18-68) responded to public and social-media advertisements. Participants virtually completed both the CAT-SUD-E and the Structured Clinical Interview for DSM-5, Research Version (SCID) to assess the validity of the CAT-SUD-E in determining whether participants met criteria for specific DSM-5 SUDs. Diagnostic classifications were based on 7 SUDs, each with 5 items, for current and lifetime SUDs., Results: For SCID-based presence of any lifetime SUD, predictions based on the overall CAT-SUD-E diagnosis and severity score were AUC=0.92, 95% CI = 0.88, 0.95 for current and AUC=0.94, 95% CI = 0.91, 0.97 for lifetime. For individual diagnoses, classification accuracy for current SUDs ranged from an AUC=0.76 for alcohol to AUC=0.92 for nicotine/tobacco. Classification accuracy for lifetime SUDs ranged from an AUC=0.81 for hallucinogens to AUC=0.96 for stimulants. Median CAT-SUD-E completion time was under 4 min., Conclusions: The CAT-SUD-E quickly produces similar results as lengthy structured clinical interviews for overall SUD and substance-specific SUDs, with high precision and accuracy, through a combination of fixed-item responses for diagnostic classification and adaptive SUD severity measurement. The CAT-SUD-E harmonizes information from mental health, trauma, social support and traditional SUD items to provide a more complete characterization of SUD and provides both diagnostic classification and severity measurement., Competing Interests: Dr. Gibbons has been an expert witness for the U.S. Department of Justice, Merck, Glaxo-Smith-Kline, Pfizer, and Wyeth and is a founder of Adaptive Testing Technologies, which distributes the CAT-MHTM battery of adaptive tests. The terms of this arrangement have been reviewed and approved by the University of Chicago in accordance with its conflict of interest policies. Dr. Hulvershorn has received support from an unrestricted grant to the National Network of Depression Treatment Centers from Greenwich Biosciences., (© 2022 The Author(s). Published by Elsevier B.V.)

Background: People with opioid use disorders (OUDs) are at heightened risk for involvement with the criminal justice system. Growing evidence supports the safety and effectiveness of providing empirically supported treatments for OUD, such as medications for OUD (M-OUD), to people with criminal justice involvement including during incarceration or upon reentry into the community. However, several barriers limit availability and accessibility of these treatment options for people with OUDs, including a shortage of healthcare and justice professionals trained in how to implement them. This study evaluated a novel education program, the Indiana Jail OUD Treatment ECHO, designed to disseminate specialty knowledge and improve attitudes about providing M-OUD in justice settings. Methods: Through didactic presentations and case-based learning (10 bimonthly, 90-min sessions), a multidisciplinary panel of specialists interacted with a diverse group of community-based participants from healthcare, criminal justice, law enforcement, and related fields. Participants completed standardized surveys about OUD knowledge and attitudes about delivering M-OUD in correctional settings. Thematic analysis of case presentations was conducted. Results: Among 43 participants with pre- and post-series evaluation data, knowledge about OUD increased and treatment was viewed as more practical after the ECHO series compared to before. Cases presented during the program typically involved complicated medical and psychiatric comorbidities, and recommendations addressed several themes including harm reduction, post-release supports, and integration of M-OUD and non-pharmacological interventions. Conclusions: Evaluation of future iterations of this innovative program should address attendance and provider behavior change as well as patient and community outcomes associated with ECHO participation.

Bipolar disorder (BD) is associated with a 20-30-fold increased suicide risk compared to the general population. First-degree relatives of BD patients show inflated rates of psychopathology including suicidal behaviors. As reliable biomarkers of suicide attempts (SA) are lacking, we examined associations between suicide-related polygenic risk scores (PRSs)-a quantitative index of genomic risk-and variability in brain structures implicated in SA. Participants (n = 206; aged 12-30 years) were unrelated individuals of European ancestry and comprised three groups: 41 BD cases, 96 BD relatives ("high risk"), and 69 controls. Genotyping employed PsychArray, followed by imputation. Three PRSs were computed using genome-wide association data for SA in BD (SA-in-BD), SA in major depressive disorder (SA-in-MDD) (Mullins et al., 2019, The American Journal of Psychiatry, 176(8), 651-660), and risky behavior (Karlsson Linnér et al., 2019, Nature Genetics, 51(2), 245-257). Structural magnetic resonance imaging processing employed FreeSurfer v5.3.0. General linear models were constructed using 32 regions-of-interest identified from suicide neuroimaging literature, with false-discovery-rate correction. SA-in-MDD and SA-in-BD PRSs negatively predicted parahippocampal thickness, with the latter association modified by group membership. SA-in-BD and Risky Behavior PRSs inversely predicted rostral and caudal anterior cingulate structure, respectively, with the latter effect driven by the "high risk" group. SA-in-MDD and SA-in-BD PRSs positively predicted cuneus structure, irrespective of group. This study demonstrated associations between PRSs for suicide-related phenotypes and structural variability in brain regions implicated in SA. Future exploration of extended PRSs, in conjunction with a range of biological, phenotypic, environmental, and experiential data in high risk populations, may inform predictive models for suicidal behaviors., (© 2021 Wiley Periodicals LLC.)

Background: Youth in the justice system (YJS) are more likely than youth who have never been arrested to have mental health and substance use problems. However, a low percentage of YJS receive SUD services during their justice system involvement. The SUD care cascade can identify potential missed opportunities for treatment for YJS. Steps along the continuum of the cascade include identification of treatment need, referral to services, and treatment engagement. To address gaps in care for YJS, we will (1) implement a learning health system (LHS) to develop, or improve upon, alliances between juvenile justice (JJ) agencies and community mental health centers (CMHC) and (2) present local cascade data during continuous quality improvement cycles within the LHS alliances., Methods/design: ADAPT is a hybrid Type II effectiveness implementation trial. We will collaborate with JJ and CMHCs in eight Indiana counties. Application of the EPIS (exploration, preparation, implementation, and sustainment) framework will guide the implementation of the LHS alliances. The study team will review local cascade data quarterly with the alliances to identify gaps along the continuum. The study will collect self-report survey measures longitudinally at each site regarding readiness for change, implementation climate, organizational leadership, and program sustainability. The study will use the Stages of Implementation Completion (SIC) tool to assess the process of implementation across interventions. Additionally, the study team will conduct focus groups and qualitative interviews with JJ and CMHC personnel across the intervention period to assess for impact., Discussion: Findings have the potential to increase SUD need identification, referral to services, and treatment for YJS., (Copyright © 2021. Published by Elsevier Inc.)

Background: Sex-specific neurobiological underpinnings of impulsivity in youth with externalizing disorders have not been well studied. The only report of functional connectivity (FC) findings in this area demonstrated sex differences in fronto-subcortical connectivity in youth with attention-deficit/hyperactivity disorder (ADHD)., Methods: The current study used functional magnetic resonance imaging(fMRI) to examine sex differences in resting-state seed-based FC, self-rated impulsivity, and their interactions in 11-12-year-old boys (n = 43) and girls (n = 43) with externalizing disorders. Generalized linear models controlling for pubertal development were used. Seeds were chosen in the ventral striatum, medial prefrontal cortex, middle frontal gyrus and amygdala., Results: Impulsivity scores were greater in boys than girls (p < 0.05). Boys showed greater positive connectivity within a ventromedial prefrontal-ventral striatal network. In addition, boys demonstrated weaker connectivity than girls within two medial-lateral prefrontal cortical networks. However, only boys showed greater medial-lateral prefrontal connectivity correlated with greater impulsivity., Conclusions: The findings provide evidence supporting sex differences in both ventral striatal-ventromedial prefrontal and medial-lateral prefrontal functional networks in youth with externalizing disorders. These important networks are thought to be implicated in impulse control. Medial-lateral prefrontal connectivity may represent a male-specific biomarker of impulsivity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Offspring of parents with substance use disorders (SUD) discount future rewards at a steeper rate on the monetary delay discounting task (DD) than typically developing youth. However, brain activation during DD has yet to be studied in drug naïve youth with a family history (FH) of SUD. Here, we investigate brain activation differences in high-risk youth during DD. We recruited substance naïve youth, aged 11-12, into three groups to compare brain activation during DD: (1) High-risk youth (n = 35) with a FH of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n = 25) who had no FH of SUD, but with equivalent externalizing psychiatric disorders as high-risk youth, and (3) a healthy control group (n = 24) with no FH of SUD and minimal psychopathology. A whole-brain voxel wise analysis of the [Delay > Baseline], [Immediate > Baseline], and [Control > Baseline] contrasts identified functional regions of interest, from which extracted parameter estimates were tested for significant group differences. Relative to control youth, high-risk youth showed stronger activation in the left posterior insula and thalamus when making delayed choices, and stronger activation of the parahippocampal gyrus when making both delayed and control choices (ps < 0.05). Activation in the left posterior insula negatively correlated with both subscales of the Emotion Regulation Checklist, and positively correlated with the Stroop interference effect (ps < 0.05). Our findings suggest possible heritable SUD risk neural markers that distinguish drug naïve high-risk youth from psychiatric and healthy controls., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Suicidality is a leading cause of death among adolescents. In addition to other psychiatric conditions, youths with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs) are at heightened risk for suicide. Decision-making deficits are a hallmark symptom of ADHD and DBDs and are also implicated in suicidal behavior. We examined behavioral and neural differences in decision making among youths with ADHD and DBDs with (SI+) and without (SI-) histories of suicidal ideation., Methods: The Balloon Analog Risk Task, a risky decision-making task, was completed by 57 youths with ADHD and DBDs (38% SI+) during functional magnetic resonance imaging. Mean stop wager (mean wager at which youths bank money) was the primary measure of risk taking. We conducted whole-brain and region-of-interest analyses in the anterior cingulate cortex and orbitofrontal cortex (OFC) during choice (win vs. inflate) and outcome (inflate vs. explode) contrasts using parametric modulators accounting for probability of balloon explosion., Results: There were no differences between SI+ and SI- youths in Balloon Analog Risk Task performance. SI+ youths showed decreasing activation in the right medial frontal gyrus when choosing inflate as explosion probability increased compared with SI- youths. During explosions, SI- youths showed increasing activation in the left OFC as explosions became more likely. SI+ showed increasing left medial OFC activity in response to inflations as explosion probability increased., Conclusions: SI+ youths may show heightened sensitivity to immediate reward and decreased sensitivity to potential loss as evidenced by medial frontal gyrus activity. OFC findings suggest that SI+ youths may be drawn to reward even when there is high probability of loss., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Little is known about how adolescents receive depression follow-up in primary care. The purpose of this study was to describe the rates of symptom assessment and depression treatment over time in a group of adolescents screening positive for moderate or severe depression in the primary care setting., Methods: Retrospective chart reviews were conducted to gather information related to symptom reassessments, antidepressant prescriptions, psychotherapy referrals, and treatment discontinuation. Descriptive statistics were calculated, and a qualitative content analysis was conducted to determine the reasons for treatment discontinuation., Results: Eighty records were reviewed (mean age = 15.3, 73% female, 59% Black). Treatment was initiated for 83% (n = 66) of patients, and 45% (n = 30) of patients discontinued treatment during the review period for a variety of reasons., Discussion: To improve adolescents' adherence to depression treatment, providers should address factors that contribute to treatment discontinuation and use tools to manage depression follow-up care., (Copyright © 2019 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Background: Youth involved in the juvenile justice system (YIJJ) have high rates of substance use problems; however, rates of YIJJ engagement in substance use services is low. Barriers to service engagement include lack of appropriate screening and connection to services by the juvenile justice system, as well as lack of resources for delivering evidence-based treatment in community-based settings. To address these barriers, this paper describes a protocol for a type 1 hybrid design to (1) implement universal substance use screening for YIJJ; (2) implement and evaluate the feasibility and effectiveness of a brief, three-session substance use interventions based in motivational interviewing for youth with mild/moderate substance use: Teen Intervene (an individual-based intervention); (3) implement ENCOMPASS, an evidence-based substance use intervention based in motivational enhancement and cognitive behavioral therapy for youth with severe substance use; and (4) evaluate facilitators and barriers to implementing these interventions for mild to severe substance use among YIJJ in community mental health centers (CMHC)., Methods/design: Using a hybrid type 1 clinical effectiveness-implementation design, we will collaborate with CMHCs and juvenile justice in two rural Indiana counties. Guided by the EPIS (exploration, preparation, implementation, sustainability) framework, we will measure factors that affect implementation of substance use screening in juvenile justice and implementation of substance use interventions in CMHCs utilizing self-reports and qualitative interviews with juvenile justice and CMHC staff pre- and post-implementation. YIJJ with mild/moderate substance use will receive a brief interventions and YIJJ with severe substance use will receive ENCOMPASS. We will measure the effectiveness of a brief and comprehensive intervention by assessing changes in substance use across treatment. We anticipate recruiting 160 YIJJ and their caregivers into the study. We will assess intervention outcomes utilizing baseline, 3-, and 6-month assessments., Discussion: Findings have the potential to improve screening and intervention services for YIJJ.

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12-21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two 'conflict classes' perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics., (Published by Elsevier Ltd.)

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability., (Copyright © 2019. Published by Elsevier B.V.)

Objective: Risk-taking during adolescence is a leading cause of mortality; Neuroscience research examining pubertal effects on decision-making is needed to better inform interventions, particularly among youth with attention-deficit/hyperactivity (ADHD) and disruptive behavior disorders (DBD), who are particularly prone to risky decision-making. We examined effects of pubertal development on risky decision-making and neural activation during decision-making among youth with ADHD/DBDs., Method: Forty-six 11-12-year-olds (29.4% girls; 54.9% white; Tanner M(SD) = 2.08(1.32)) who met DSM-5 criteria for ADHD/DBD completed the Balloon Analog Risk Task (BART) during fMRI scanning. We examined effects of Tanner stage, sex, and age on risky decision-making (mean wager at which individuals stopped balloon inflation) and neural activation in the middle frontal gyrus and the ventral striatum during the choice and outcome phases of decision-making., Results: Those in earlier pubertal stages made riskier decisions during the BART compared to those in later Tanner stages (β=-0.62, p =  .02). Later pubertal stage was associated with greater activation in the left middle frontal gyrus (β=0.61, p = .03) during the choice phase and in the right ventral striatum in response to rewards (β=0.59, p = .03)., Conclusion: Youth with ADHD/DBD in later stages of puberty, regardless of age, show greater ventral striatal activation in response to rewards., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Substance use and unprotected sex are prevalent among adolescents. The link between substance use and unprotected sex is well-established. Research has also highlighted how adolescents' attitudes and risk perceptions regarding unprotected sex, including concerns about pregnancy ("Getting pregnant would force me to grow up too fast"), are associated with unprotected sex and unplanned pregnancy. However, less research has examined the potential relationship between pregnancy concerns and substance use among adolescents., Objectives: The study prospectively examined (1) differences in pregnancy concerns across patterns of substance use and (2) whether pregnancy concerns mediate the relationship between substance use and later unprotected sex among a sample of middle and high school students., Method: 98 adolescents [M(SD) age = 14.28(1.68), 59.4% female, 59.4% black/African American] completed self-report measures of marijuana and alcohol use, pregnancy concerns, and unprotected sex across three time points over 6 months (T1-T3)., Results: Substance users (alcohol/marijuana) reported fewer pregnancy concerns compared to non-substance users (t = 2.99, p = .04). Pregnancy concerns at T2 mediated the relationship between T1 lifetime substance use and later unprotected sex (T3) (indirect effect: b = 0.10, CI[.01-.41]; direct effect: b = 0.15, p = .32), controlling for gender, age, and race. More frequent substance use (T1) was related to fewer pregnancy concerns at T2 (b = -0.10, p = .04); fewer pregnancy concerns were related to increased likelihood of later unprotected sex (b = -1.02, p = .02)., Conclusions: Findings offer new insight into associations between substance use and unprotected sex and suggest that substance use and sexual health interventions should target pregnancy concerns.

Objective: The purpose of this open-label study was to examine the effects of long-acting methylphenidate (MPH) treatment on irritability and related emotional symptoms associated with disruptive mood dysregulation disorder (DMDD) in youth with comorbid attention-deficit/hyperactivity disorder (ADHD)., Methods: The sample included 22 medication-free male and female subjects (ages 9-15) who met criteria for both DMDD and ADHD. Participants underwent a 4-week trial of long-acting MPH treatment (Concerta ® ), with weekly dosing increases until a therapeutic dose was reached. Repeated measures t-tests were used to compare pre- and posttreatment ratings of primary and secondary measures. The primary outcome was self-report irritability. Secondary outcomes included parent and child ratings of emotional frequency, emotional lability, and negative affect (NA). Multiple regression was used to examine the impact baseline hyperactivity, age, gender, race, socioeconomic status, or comorbid diagnosis had on treatment outcomes., Results: Significant improvements (medium to large effect sizes) in child-rated irritability as well as parent and child ratings of emotional lability, NA, and anger were found. As anticipated, ADHD symptoms also improved. While a majority of the sample saw improvement in child-rated irritability (71%), symptoms worsened a small proportion (19%), and an even smaller portion experienced no change (10%). No demographics, psychiatric comorbidities, or severity of ADHD symptoms influenced treatment outcomes., Conclusions: Study findings suggest that MPH treatment significantly improved mood and emotional symptoms associated with DMDD comorbid with ADHD. These findings, coupled with good tolerability in this open-label pilot study supports further research into the use of MPH as a first-line treatment for DMDD. Future work examining MPH treatment of youth with DMDD with and without comorbid ADHD is needed.

Purpose of Review: The goal of this paper is to review recent research on the identification and treatment of prodromal periods that precede bipolar and psychotic disorders. We also sought to provide information about current best clinical practices for prodromal youth., Recent Findings: Research in the areas of identifying prodromal periods has rapidly advanced. Calculators that can predict risk are now available for use during both bipolar and psychotic disorder prodromes. Cognitive behavior therapies have emerged as the gold standard psychosocial interventions for the psychosis prodrome, while several other types of therapies hold promise for treatment during the bipolar prodrome. Due to safety and efficacy concerns, pharmacologic treatments are not currently recommended during either prodromal period., Summary: While additional research is needed to develop useful clinical tools to screen and diagnose during prodromal phases, existing literature has identified constellations of symptoms that can be reliably identified in research settings. Specialized psychotherapies are currently recommended to treat prodromal symptoms in clinical settings. They may also be useful to curtail future episodes, although further research is needed., Competing Interests: Conflict of Interest Susan Conroy, Michael Francis and Leslie Hulvershorn declare that they have no conflicts of interest.

Alcohol use, particularly binge drinking (BD), is a major public health concern among adolescents. Recent national data show that the gender gap in alcohol use is lessening, and BD among girls is rising. Considering the increase in BD among adolescent girls, as well as females' increased risk of experiencing more severe biopsychosocial negative effects and consequences from BD, the current review sought to examine gender differences in risk factors for BD. The review highlights gender differences in (1) developmental-related neurobiological vulnerability to BD, (2) psychiatric comorbidity and risk phenotypes for BD, and (3) social-related risk factors for BD among adolescents, as well as considerations for BD prevention and intervention. Most of the information gleaned thus far has come from preclinical research. However, it is expected that, with recent advances in clinical imaging technology, neurobiological effects observed in lower mammals will be confirmed in humans and vice versa . A synthesis of the literature highlights that males and females experience unique neurobiological paths of development, and although there is debate regarding the specific nature of these differences, literature suggests that these differences in turn influence gender differences in psychiatric comorbidity and risk for BD. For one, girls are more susceptible to stress, depression, and other internalizing behaviors and, in turn, these symptoms contribute to their risk for BD. On the other hand, males, given gender differences across the lifespan as well as gender differences in development, are driven by an externalizing phenotype for risk of BD, in part, due to unique paths of neurobiological development that occur across adolescence. With respect to social domains, although social and peer influences are important for both adolescent males and females, there are gender differences. For example, girls may be more sensitive to pressure from peers to fit in and impress others, while male gender role stereotypes regarding BD may be more of a risk factor for boys. Given these unique differences in male and female risk for BD, further research exploring risk factors, as well as tailoring intervention and prevention, is necessary. Although recent research has tailored substance use intervention to target males and females, more literature on gender considerations in treatment for prevention and intervention of BD in particular is warranted.

Objective: Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls)., Method: Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score., Results: After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041)., Conclusion: BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized., Methods: We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006-2011. Youth offspring/relatives ("Relatives of BD probands;" n=267; mean age=16.8years; ±2.9S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands ("relatives of control probands;" n=149; mean age=17.4years; ±2.9S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes., Results: Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p=0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR=2.80-3.17; p<0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves., Conclusion: Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Specific treatments targeting adolescents with substance use disorders (SUDs) have been developed over the last couple of decades. Despite these developmentally tailored treatments, long-term abstinence rates remain relatively low among adolescents receiving care. Research over the last decade has increasingly focused on adolescents with comorbid substance use and psychiatric disorders, in recognition of the barriers caused by inadequate treatment of co-occurring psychiatric disorders. Treatments targeting dually diagnosed youth are now regarded as essential to improving SUD treatment outcomes, but remain underutilized. A variety of treatment modalities such as behavioral therapy, family therapy, 12-step groups, motivational interviewing, contingency management, and combinations of these interventions have been modified for adolescents. In this article, we review the research on these treatments, as they apply to dually diagnosed youth. Furthermore, we explore the evidence for various treatments targeting comorbid SUD, specific to the presence of externalizing or internalizing disorders. The current evidence base supports the importance of integrated treatment targeting both SUD and psychiatric disorders simultaneously. High-quality treatment programs offering combinations of behavioral and family therapy, particularly with motivational interviewing and contingency management, are particularly well supported. In addition, we review various psychotropic medication treatments that have also been studied in conjunction with adolescent SUD treatment. Finally, we review research on post-treatment, supportive care that has been shown to improve long-term SUD outcomes. Recently conceptualized modular treatments, which offer personalized combinations of evidence-based treatments for specific disorders, have been proposed as a means of improving outcomes. Future research on modular programs must test the efficacy of individualized treatments when applied to combinations of psychiatric and SUDs in adolescents.

Research on resting functional brain networks in bipolar disorder (BP) has been unable to differentiate between disturbances related to mania or depression, which is necessary to understand the mechanisms leading to each state. Past research has also been unable to elucidate the impact of BP-related network disturbances on the organizational properties of the brain (eg, communication efficiency). Thus, the present work sought to isolate network disturbances related to BP, fractionate these into components associated with manic and depressive symptoms, and characterize the impact of disturbances on network function. Graph theory was used to analyze resting functional magnetic resonance imaging data from 60 medication-free patients meeting the criteria for BP and either a current hypomanic (n=30) or depressed (n=30) episode and 30 closely age/sex-matched healthy controls. Correction for multiple comparisons was carried out. Compared with controls, BP patients evidenced hyperconnectivity in a network involving right amygdala. Fractionation revealed that (hypo)manic symptoms were associated with hyperconnectivity in an overlapping network and disruptions in the brain's 'small-world' network organization. Depressive symptoms predicted hyperconnectivity in a network involving orbitofrontal cortex along with a less resilient global network organization. Findings provide deeper insight into the differential pathophysiological processes associated with hypomania and depression, along with the particular impact these differential processes have on network function.

Rational: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability., Objectives: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes., Methods: Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12)., Results: In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R 2  = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R 2  = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement., Conclusions: These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.

Introduction: The purpose of the study was to better understand early risk for positive smoking expectancies, which have been shown to be consistent predictors of smoking initiation among youth. Two affect-based risk factors-negative urgency and emotion dysregulation-associated with smoking behaviors among youth, were examined for unique and interactive effects on positive smoking expectancies among substance-naïve youth., Methods: Participants were 61 10-14-year-old children with virtually no drug use (less than 5 substance use incidents across the lifetime), who were drawn from the community., Results: Both negative urgency and emotion dysregulation were significantly associated with positive social facilitation smoking expectancies. Further, negative urgency was significantly related to positive social facilitation smoking expectancies at higher levels of emotion dysregulation (b=.09, p=.001)., Conclusion: The findings provide evidence that both emotion dysregulation and negative urgency are positively associated with positive social-related smoking expectancies among a sample of 10-14-year-olds. Children who are emotionally dysregulated and who act rashly in response to negative emotions appear more likely to endorse beliefs regarding the socially enhancing effects of smoking, suggesting that these youth may be at high risk for smoking initiation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related.