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Abstract 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.

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.

Abstract 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

OBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.

Abstract 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.

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.

Objective. In 1998, Felitti and colleagues published the first study of the Adverse Childhood Experiences-Questionnaire (ACE-Q), a 10-item scale used to correlate childhood maltreatment and adverse rearing contexts with adult health outcomes. This paper qualitatively reviews nearly two decades of research utilizing the ACE-Q, highlighting its contribution to our understanding of the causal roots of common, interlinked comorbidities of the brain and body. Methods. An OVID/PubMed search was conducted for English language articles published before 2016, containing the phrase “Adverse Childhood Experiences” in which the ACE-Q was utilized. Source review included a manual search of bibliographies, resulting in 134 articles, including 44 based on the original ACE-Q study population. Results. ACE-Q research has demonstrated that exposures to adverse childhood experiences converge dose-dependently to potently increase the risk for a wide array of causally interlinked mental illnesses, addictions, and multi-organ medical diseases. The intergenerational transmission of this disease burden via disrupted parenting and insecure rearing contexts is apparent throughout this literature. However, the ACE-Q does not tease out genetic or fetal drug exposure components of this transmission. Conclusions. Adverse childhood experiences and rearing may generate a public health burden that could rival or exceed all other root causes. Translating this information to health-care reform will require strengthening brain-behavioral health as core public and preventative health-care missions. Greater integration of mental health and addiction services for parents should be accompanied by more research into brain mechanisms impacted by different forms and interactions between adverse childhood experiences.