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.

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.

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.

Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial.

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.

Use of Project ECHO to promote evidence based care for justice involved adults with opioid use disorder.

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.

Effects of polygenic risk for suicide attempt and risky behavior on brain structure in young people with familial risk of bipolar disorder.

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.

The Role of Pregnancy Concerns in the Relationship between Substance Use and Unprotected Sex among Adolescents.

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.

Altered intrinsic functional connectivity of the cingulate cortex in children with severe temper outbursts.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

Treating Mental Health and Substance Use Disorders in Adolescents: What Is on the Menu?

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.

Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk?

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.

Psychopharmacologic treatment of children prenatally exposed to drugs of abuse.

OBJECTIVE: This pilot study compared the pharmacologic treatment history and clinical outcomes observed in pediatric outpatients with psychiatric disorders exposed to drugs of abuse in utero to those of an age-matched, sex-matched and psychiatric disorder-matched, non-drug-exposed group. METHODS: In this matched cohort study, medical records of children treated at an academic, child and adolescent psychiatry outpatient clinic were reviewed. Children with caregiver-reported history of prenatal drug exposure were compared with a non-drug-exposed control group being cared for by the same providers. Patients were rated with the Clinical Global Impressions-Severity scale (CGI-S) throughout treatment. The changes in pre-treatment and post-treatment CGI-S scores and the total number of medication trials were determined between groups. RESULTS: The drug-exposed group (n = 30) had a higher total number of lifetime medication trials compared with the non-drug-exposed group (n = 28) and were taking significantly more total medications, at their final assessment. Unlike the non-drug-exposed group, the drug-exposed group demonstrated a lack of clinical improvement. CONCLUSIONS: These results suggest that in utero drug-exposed children may be more treatment-refractory to or experience greater side effects from the pharmacologic treatment of psychiatric disorders than controls, although we cannot determine if early environment or drugs exposure drives these findings.

Using stimulants to treat ADHD-related emotional lability.

Emotional lability, or sudden strong shifts in emotion, commonly occurs in youth with attention-deficit/hyperactivity disorder. Although these symptoms are impairing and disruptive, relatively little research has addressed their treatment, likely due to the difficulty of reliable and valid assessment. Promising signals for symptom improvement have come from recent studies using stimulants in adults, children and adolescents. Similarly, neuroimaging studies have begun to identify neurobiological mechanisms underlying stimulants' impact on emotion regulation capacities. Here, we review these recent clinical and neuroimaging findings, as well as neurocognitive models for emotional lability in ADHD, issues of relevance to prescribers and the important role of psychiatric comorbidity with treatment choices.

Temporal interference electrical neurostimulation at 20 Hz beat frequency leads to increased fMRI BOLD activation in orbitofrontal cortex in humans.

Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain regions without stimulating the overlying superficial regions. Although some recent studies have demonstrated the success of TI in modulating task-induced BOLD activity in humans, there is limited information on intended and off-target effects of TI during resting-state. We simultaneously performed TI stimulation with the set-up optimized for maximum focality in the left caudate and collected resting-state fMRI data to investigate the effects of TI on human BOLD signals. We found increased BOLD activation in a part of the mid-orbitofrontal cortex (OFC) and parahippocampal gyrus. Results indicate that TI can induce increased BOLD activation in the region that receives the highest magnitude of TI amplitude modulation in humans, with good safety and tolerability profiles. We also show the limits of spatial precision and explore the nature and causes of additional off-target effects. TI may be a promising approach for addressing questions about the causal role of deep brain structures in human cognition and may also afford new clinical treatments.

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.

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.

"Just as expensive as sending him to college:" barriers and perceptions of treatment in justice-involved youth.

BACKGROUND: Justice-involved youth have higher rates of substance use disorders (SUDs) than the general population. Many do not connect with or complete treatment, leading to recidivism. This qualitative study explores perceptions and barriers to treatment in this population. RESULTS: Justice-involved youth participating in a larger study focused on access to SUD treatment were interviewed about available treatment and justice system involvement. Twenty-one dyads (youth and a guardian) and 3 individual guardians (total N = 45) were interviewed by phone. Inclusion criteria were youth aged 14-17 involved in the justice system that screened positive for SUD. Youth sample was 43% male. Thematic analysis guided the process. The study was Indiana University Institutional Review Board approved (#1802346939). Data was interpreted within the ecological system theory. Youth barriers included willingness to engage in treatment, time constraints/scheduling conflicts, and low perceived usefulness of treatment. Major guardian themes included high cost of treatment, lack of communication by the justice system about treatment, youth unwillingness or disinterest to engage in treatment, and limited program availability. CONCLUSIONS: The barriers to treatment for justice-involved youth are multifaceted and occur across the spectrum of levels of the ecological system, which include parents, peers, social systems, and cultural elements. Many youth and guardians suggested improvements for their interactions with the juvenile justice system. Further examination is needed of current policy implementation to address these concerns.

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.

Examining the association of familial and social stress, trauma, and support on mood, anxiety, and behavioral symptoms and diagnoses in youth at risk for bipolar disorder and controls.

INTRODUCTION: Youth with a family history of bipolar disorder (At-Risk) have a higher risk of developing psychiatric disorders and experiencing environmental stressors than youth without such family history (Control). We studied the differential associations of familial and environmental factors on developing psychiatric diagnoses and symptoms, in At-Risk and Control youth. METHODS: At-Risk and Control youth (N = 466, ages 9-22) were systematically assessed for severity of symptoms, psychiatric diagnoses, and self-reported measures of stress and social support. We tested the association of family history and measures of stress or support with symptom severity and diagnoses. RESULTS: At-Risk youth had higher symptom severity scores and were more frequently diagnosed with psychiatric disorders (all p values < 0.001). When predicting mood symptom severity, family history had an interaction effect with stressful life events (p < 0.001) and number of distinct traumatic events (p = 0.001). In multivariate models, At-Risk status predicted anxiety disorders (OR = 2.7, CI 1.3-5.4, p = 0.005) and anxiety severity (Coefficient = 0.4, CI 0.2-0.7, p < 0.001) but not mood or behavioral disorder diagnoses or severity. LIMITATIONS: Measures of stress and social support were based on self-report. Not all participants had passed through the period of risk for developing the outcomes under study and the follow up period was variable. We could not fully study the differential impact of physical or sexual abuse due to low frequency of occurrence in controls. CONCLUSION: At-Risk youth exhibit more severe mood symptoms compared to Controls when exposed to similar levels of stress or trauma. At-Risk youth are also more prone to develop anxiety which may be a precursor for bipolar disorder.

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.