A Statewide Consultation Helpline for Rapid Linkage to Services for Youths With Opioid Use Disorder and Other Substance Use.

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.

Attitudes toward and training in medications for opioid use disorders: a descriptive analysis among employees in the youth legal system and community mental health centers.

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.

Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression.

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.

Utility of the Leadership and Organizational Change for Implementation-Systems Level (LOCI-SL) strategy for a statewide substance use treatment implementation effort.

INTRODUCTION: Multi-level and cross-context implementation strategies are needed to support health systems, healthcare delivery organizations, and providers to adopt evidence-based practice (EBP) for substance use disorder (SUD) treatment. However, misalignment between state oversight agencies and healthcare organizations about which services to prioritize and which outcomes are reasonable to expect can hinder implementation success and widespread access to high-quality care. This study investigated the utility of the Leadership and Organizational Change for Implementation-System Level (LOCI-SL) strategy for supporting statewide EBP implementation for SUD treatment. METHODS: Nine community mental health centers (CMHCs) contracted by a state agency participated in a combined motivational-enhancement therapy and cognitive behavioral therapy (MET/CBT) implementation effort. Five of the CMHCs also received the LOCI-SL strategy to obtain ongoing implementation support. We conducted 21 individual interviews and three small group interviews with 30 participants across CMHCs and state health agencies to investigate the utility of LOCI-SL in supporting their EBP implementation efforts. Deductive thematic analysis was guided by the Exploration, Preparation, Implementation, Sustainment Framework. RESULTS: Five themes described CMHCs' LOCI-SL and broader contextual experiences implementing EBPs: (1) LOCI-SL supported executives in Preparation phase activities that holistically considered organizational needs and capacity to implement and sustain EBPs; (2) LOCI-SL facilitated trust and communication processes across Preparation, Implementation, and Sustainment phases to improve EBP uptake; (3) LOCI-SL increased CMHCs' use of implementation climate strengthening activities throughout the Implementation phase; (4) state contracts did not emphasize quality and thus were not sufficient bridging factors to enforce EBP fidelity during Implementation; and, (5) limited funding and low Medicaid reimbursement rates hindered EBP use throughout the Implementation and Sustainment phases. CONCLUSIONS: LOCI-SL was viewed as a favorable and useful implementation strategy for supporting statewide adoption of EBPs. However, outer context barriers, including limited financial investments in the treatment system, impeded implementation and sustainment efforts. While previous research suggests that contracts are viable alignment-promoting bridging factors, this study demonstrates the importance of articulating implementation outcome expectations to aid state-contracted organizations in achieving EBP implementation success. This study also highlights the need for multi-level implementation strategies to effectively align implementation expectations between outer- and inner-context entities.

Early development of local data dashboards to depict the substance use care cascade for youth involved in the legal system: qualitative findings from end users.

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.

Initial Validation of a Computerized Adaptive Test for Substance Use Disorder Identification in Adolescents.

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.

CANNABIS USE AND THE DEVELOPING BRAIN: HIGHS AND LOWS.

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.

User-Guided Enhancements to a Technology-Facilitated Resilience Program to Address Opioid Risks Following Traumatic Injury in Youth: Qualitative Interview Study.

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.

Treatment of Adolescent Cannabis Use Disorders.

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.

Family history of substance use disorder and parental impulsivity are differentially associated with neural responses during risky decision-making.

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.

Family environment and polygenic risk in the bipolar high-risk context.

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.

Evidence-based Treatment for Substance Use Disorders in Community Mental Health Centers: the ACCESS Program.

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.

Association of Antipsychotic-Related Weight Gain With Treatment Adherence and Switching Using Electronic Medical Records Data.

Objective: To leverage electronic health record (EHR) data to explore the relationship between weight gain and antipsychotic adherence among patients with schizophrenia and bipolar disorder (BD).Methods: EHR data were used to identify individuals with at least 60 days of continuous antipsychotic use between 2005 and 2019. Patients were diagnosed with schizophrenia, schizoaffective disorder, BD, or neither diagnosis (psychiatric controls). We examined the association of weight gain in the first 90 days with the proportion of days covered (PDC) with an antipsychotic and with the frequency of medication switching or stopping.Results: We identified 590 adults with schizophrenia or schizoaffective disorder, 819 adults with BD, and 642 psychiatric controls. In the first 90 days, the percentages of patients with a PDC ≥ 0.80 were 76.8% (schizophrenia), 77.1% (BD), and 70.7% (controls). Logistic regression models revealed that weight gain of ≥ 7% trended toward being significantly associated with greater adherence in the first 90 days (odds ratio = 1.29, P = .077) and was significantly associated with an increased likelihood of a medication switch in the first 180 days (odds ratio = 1.60, P = .003).Discussion: Patients whose weight increased by 7% or more in the first 90 days were more adherent but were also more likely to switch medications during the first 180 days.

Association Between Head Impact Exposure, Psychological Needs, and Indicators of Mental Health Among U.S. High School Tackle Football Players.

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 (ß = -0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (ß = -0.021, SE = 0.008, p = .010), and greater thriving scores (ß = 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.

The impact of antipsychotic adherence on acute care utilization.

BACKGROUND: Non-adherence to psychotropic medications is common in schizophrenia and bipolar disorders (BDs) leading to adverse outcomes. We examined patterns of antipsychotic use in schizophrenia and BD and their impact on subsequent acute care utilization. METHODS: We used electronic health record (EHR) data of 577 individuals with schizophrenia, 795 with BD, and 618 using antipsychotics without a diagnosis of either illness at two large health systems. We structured three antipsychotics exposure variables: the proportion of days covered (PDC) to measure adherence; medication switch as a new antipsychotic prescription that was different than the initial antipsychotic; and medication stoppage as the lack of an antipsychotic order or fill data in the EHR after the date when the previous supply would have been depleted. Outcome measures included the frequency of inpatient and emergency department (ED) visits up to 12 months after treatment initiation. RESULTS: Approximately half of the study population were adherent to their antipsychotic medication (a PDC ≥ 0.80): 53.6% of those with schizophrenia, 52.4% of those with BD, and 50.3% of those without either diagnosis. Among schizophrenia patients, 22.5% switched medications and 15.1% stopped therapy. Switching and stopping occurred in 15.8% and 15.1% of BD patients and 7.4% and 20.1% of those without either diagnosis, respectively. Across the three cohorts, non-adherence, switching, and stopping therapy were all associated with increased acute care utilization, even after adjusting for baseline demographics, health insurance, past acute care utilization, and comorbidity. CONCLUSION: Non-continuous antipsychotic use is common and associated with high acute care utilization.

Impulsivity as a Predictor of Early Dating Initiation in 11-12-Year-Old Youth.

As early initiation of dating behaviors is associated with risky sexual behaviors (e.g., higher number of sexual partners, sex with strangers), the current study examined determinants of early dating behaviors, focusing on impulsivity. Participants were 11-12-year-old boys (n = 109) and girls (n = 61) recruited from a psychiatric clinic and ads targeted to the general public. Ordered logistic regression models were used to examine the association between each facet of impulsivity (negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking) and dating behaviors. Youth with higher sensation seeking and negative urgency was more likely to initiate dating behaviors at early ages compared to those with lower scores on those measures. Further, we found that female gender and higher parental education were associated with lower risk of initiating dating behaviors at early age. Advanced pubertal development was associated with higher risk for early dating. Our findings can inform prevention efforts, identifying sensation seeking and negative urgency as predictors of youths' early engagement in dating behaviors, which can be a precursor of early sexual debut and risky sexual behaviors.

Treatment of Adolescent Cannabis Use Disorders.

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.

Rates of Tobacco Use Disorder, Pharmacologic Treatment, and Associated Mental Health Disorders in a Medicaid Claim Review Among Youth in Indiana, USA.

Purpose: This study delineates a number of Medicaid youth with tobacco use disorder (TUD), prescribing habits for treatment, and associated externalizing disorders. Methods: Youth Medicaid claims from 2007-2017 processed in a large Midwestern city were analyzed for a diagnosis of TUD, related pharmacotherapy, and externalizing mental health and substance use disorders. Results: Claims connected 6541 patients with 42 890 visits. Mean age was 16.4 with 40% female. 1232 of the 6541 charts contained a TUD diagnosis equating to 1848 visits. A comorbid diagnosis of ADHD, cannabis use, and conduct disorder were more common in males (3.9% vs 1.3% in females; 3.4% vs .8%; and 2.8% vs .8%; P < .05). 808 scripts were provided to 152 of the 1232 youths, with 4.7% of those scripts a nicotine replacement product. Conclusions: Pharmacotherapy is underutilized in this Medicaid claims data set. Certain externalizing factors were associated with males with TUD more than females.

Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder.

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.

Editorial: The Epidemiology and Cognitive Characteristics of Attention-Deficit/Hyperactivity Disorder Depend on How Strictly the Disorder Is Defined.

In this month's issue of the Journal, Cordova et al.1 advance knowledge in our field by leveraging the Adolescent Brain Cognitive Development (ABCD) Study dataset to characterize the prevalence and comorbidities of attention-deficit/hyperactivity disorder (ADHD) in a large community sample. The ABCD dataset2 is useful because it is one of the largest samples of its kind (N = 11,878) and includes data from multiple measures and from multiple informants. This allows for sophisticated latent variable approaches to define ADHD from both a categorical and a dimensional perspective. Latent variables are variables that are not directly observed but are detected via measurement of other directly observed variables and statistical modeling.3.