Faculty Bibliography

RATIONALE/BACKGROUND:Minority sexual identity appears to confer asthma risks. Although associations between inhaled substances and asthma are established, these have not been examined among sexual minority youths. Given sexual minority adolescents' disproportionately high rates of substance use, research is needed to fill this important gap. OBJECTIVES/OBJECTIVE:Using a representative sample of adolescents from the United States, we: 1) examined associations among asthma, sexual identity, and inhaled substance use; and tested 2a) whether sexual identity moderates relationships between asthma and inhaled substance use; and 2b) whether inhaled substance use mediates associations between sexual identity and asthma. METHODS:Data are from the 2015 and 2017 Youth Risk Behavior Surveillance Survey. Adolescents (n=30,113) reported if they were ever diagnosed with asthma, current use of cigarettes, cigars/cigarillos, marijuana and electronic vapor products, and if they ever used inhalants or synthetic marijuana. We used logistic regression to examine associations between asthma, sexual identity, and inhaled substance use controlling for age, race/ethnicity, and BMI percentile, stratified by sex/gender. RESULTS:Lesbian, gay, and bisexual respondents had higher relative risks for asthma than heterosexual youth. Sexual minority female youths had significantly higher relative risks than heterosexual female youths for use of every inhaled substance. There were few sexual identity differences in inhaled substance use among male youths. Inhaled substance use was significantly associated with higher risks for asthma. In general, associations between each individual inhaled substance and asthma did not differ between sexual minority and heterosexual youths. However, when all inhaled substances were added into the models concurrently, inhaled substance use appeared to mediate associations with asthma among lesbian and bisexual female youths, and partially mediated these associations among sexual minority male youths. CONCLUSIONS:Sexual identity and inhaled substance use appear to play important roles in asthma risk. However, these variables do not fully explain the risk suggesting other unmeasured variables (e.g., stress and victimization), may be implicated in risks for both inhaled substance use and asthma. It is important that clinicians providing care to adolescents ask about sexual identity and inhaled substance use. Effective approaches to reducing inhaled substance use among adolescents, especially sexual minorities, are needed.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

OBJECTIVE:Resting-state fMRI (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Systematically identify, assess and summarize within-patient R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research. METHOD/METHODS:Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices. RESULTS:We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16-38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility. CONCLUSION/CONCLUSIONS:In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica-tion is prescribed, with second-generation antipsychotics usually preferred to first-generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence-based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves "recovery-oriented", it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient's needs in terms of employment, housing, self-care, social relationships and education, and offers a focus on identity, meaning and resilience.

Latinx youth are less likely to receive mental health services (MHS) than their non-Hispanic White counterparts. Disparities in MHS use have also been shown to vary by type of mental health problem and indices of caregiver culture even within Latinx samples, suggesting the need to go beyond cross-group racial/ethnic comparisons. However, much of the current research examining these within-group disparities has failed to directly measure the extent to which these differences are associated to specific culture. The present study utilized data from the Patterns of Care Study to examine the ways in which caregiver acculturation or enculturation is related to the MHS use of Latinx youth (N = 308) over a 2- year period. Results demonstrated that caregiver acculturation significantly moderated the relationship between caregiver ratings of internalizing need and MHS use, such that the likelihood that Latinx youth with internalizing need would receive MHS increased as caregiver acculturation increased. Furthermore, the influence of caregiver acculturation appeared to be specific to youth with internalizing need. The relationship between externalizing need and MHS utilization was not moderated by either caregiver acculturation nor enculturation. This research provides evidence that ethnic disparities in service use among Latinx families cannot be explained by race/ethnicity alone, and that additional explanatory factors need to be considered in order to gain a better understanding of the factors that drive MHS disparities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognitive behavioral therapy (CBT) is well established as an efficacious treatment for anxious youth, yet a number of youth remain symptomatic after the 10-16 sessions of treatment stipulated by most CBT treatment manuals. While a significant minority do not respond, no study has examined the frequency and impact of additional therapy sessions. This study examined youth receiving outpatient therapy at an anxiety clinic who were offered the option to continue treatment after completing 16 sessions of manual-based CBT. Fifty-nine percent of participants chose to continue treatment, with an average of approximately 20 total sessions across participants. Therapist ratings demonstrated a significant overall improvement between session 16 and the final session. No pre-treatment measure of symptom severity differed between those who extended treatment and those who ended at session 16. Parent-rated anxiety differed between groups at session 16, as did the length of time between the pre-treatment assessment and week 16 assessments. Findings indicate that extending treatment is not uncommon, is typically limited to several additional sessions, and is associated with an increase in treatment gains. Current results suggest that two factors at session 16, parental perceptions of anxiety and time to complete 16 sessions, are influential and may be central to the decision to continue treatment past this point. Clinical implications and future directions are discussed.

The present study evaluates the updating of long-term memory for duration. After learning a temporal discrimination associating one lever with a standard duration (4 sec) and another lever with both a shorter (1-sec) and a longer (16-sec) duration, rats underwent a single session for learning a new standard duration. The temporal generalization gradient obtained 24 h later showed a modification in long-term memory for durations longer than the standard but only when the new duration was longer than the one initially learned. The effect was confirmed for another set of durations (0.5-2-8 sec). Our study demonstrates asymmetry in updating long-term memory for time.

Recent research on genomic profiling of pancreatic ductal adenocarcinoma (PDAC) has identified many potentially actionable alterations. However, the feasibility of using genomic profiling to guide routine clinical decision making for PDAC patients remains unclear. We retrospectively reviewed PDAC patients between October 2013 and December 2017, who underwent treatment at the Johns Hopkins Hospital and had clinical tumor next-generation sequencing (NGS) through commercial resources. Ninety-two patients with 93 tumors tested were included. Forty-eight (52%) patients had potentially curative surgeries. The median time from the tissue available to the NGS testing ordered was 229 days (interquartile range 62-415). A total of three (3%) patients had matched targeted therapies based on genomic profiling results. Genomic profiling guided personalized treatment for PDAC patients is feasible, but the percentage of patients who receive targeted therapy is low. The main challenges are ordering NGS testing early in the clinical course of the disease and the limited evidence of using a targeted approach in these patients. A real-time department level genomic testing ordering system in combination with an evidence-based flagging system for potentially actionable alterations could help address these shortcomings.

Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene's relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.