Faculty Bibliography

BACKGROUND/UNASSIGNED:Pragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored. METHODS/UNASSIGNED: = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points. RESULTS/UNASSIGNED:Pragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups. CONCLUSION/UNASSIGNED:Overlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.

OBJECTIVE:To describe a sample of minoritized youth who screened positive for suicide risk within medical subspecialty pediatrics, compared to non-minoritized youth and describe the screening outcomes of these youth. METHODS:This retrospective chart review from October 2018 to April 2021 used electronic medical record data from an academic pediatric medical subspecialty clinic that screens universally for suicide risk for all patients ages 9 and up. Chart reviews were conducted for 237 minoritized youth (operationalized as identifying as non-White or Hispanic/Latinx, identifying as a gender minority, and having a preferred language other than English) who screened positive for suicide risk. Descriptive statistics include need for escalation to an emergency room, connection to mental health care, receival of a mental health referral, and attendance at follow-up visits. RESULTS:Minoritized youth were more likely to screen positive and report a history of suicide attempt when compared to non-minoritized peers. Youth identifying as gender expansive had significant elevation in suicide risk. The majority of youth in this sample were already connected to mental health care, with youth preferring a language other than English being the least likely to be connected. CONCLUSIONS:Findings indicate heightened suicide risk for minoritized youth, with gender expansive youth having particularly elevated suicide risk. A need to support youth with a preferred language other than English in getting connected to mental health care was also revealed.

Olanzapine is one of the most widely used antipsychotics since its initial approval by the US Food and Drug Administration in 1996 and has undergone extensive pharmacokinetic study. Despite being utilized in clinical psychiatry for decades, there remain questions regarding the variety of available formulations, the utility of therapeutic drug monitoring, altered kinetic properties in special populations/medical illnesses, the use of high-dose olanzapine, and drug interactions, among many others. We performed a narrative literature review of olanzapine pharmacokinetics in June 2023 using the US National Library of Medicine's PubMed.gov resource (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar. Herein, we review clinically relevant aspects of olanzapine pharmacokinetic data while highlighting knowledge gaps and potential areas of future study.

OBJECTIVE:Examine social media experiences of the suicidal adolescent presenting to the emergency department with an acute mental health crisis. METHODS:We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders. RESULTS:Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory. CONCLUSIONS:Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality.

BACKGROUND:Understanding mental health treatment preferences of adolescents and youth is particularly important for interventions to be acceptable and successful. Person-centered care mandates empowering individuals to take charge of their own health rather than being passive recipients of services. METHODS:We conducted a discrete choice experiment to quantitatively measure adolescent treatment preferences for different care characteristics and explore tradeoffs between these. A total of 153 pregnant adolescents were recruited from two primary healthcare facilities in the informal urban settlement of Nairobi. We selected eight attributes of depression treatment option models drawn from literature review and previous qualitative work. Bayesian d-efficient design was used to identify main effects. A total of ten choice tasks were solicited per respondent. We evaluated mean preferences using mixed logit models to adjust for within subject correlation and account for unobserved heterogeneity. RESULTS:Respondents showed a positive preference that caregivers be provided with information sheets, as opposed to co-participation with caregivers. With regards to treatment options, the respondents showed a positive preference for 8 sessions as compared to 4 sessions. With regards to intervention delivery agents, the respondents had a positive preference for facility nurses as compared to community health volunteers. In terms of support, the respondents showed positive preference for parenting skills as compared to peer support. Our respondents expressed negative preferences of ANC service combined with older mothers as compared to adolescent friendly services and of being offered refreshments alone. A positive preference was revealed for combined refreshments and travel allowance over travel allowance or refreshments alone. A number of these suggestions were about enhancing their experience of maternity clinical care experience. CONCLUSION/CONCLUSIONS:This study highlights unique needs of this population. Pregnant adolescents' value responsive maternity and depression care services offered by nurses. Participants shared preference for longer psychotherapy sessions and their preference was to have adolescent centered maternal mental health and child health services within primary care.

BACKGROUND:Internalizing and externalizing problems account for over 75% of the mental health burden in children and adolescents in the US, with higher burden among minority children. While complex interactions of multilevel factors are associated with these outcomes and may enable early identification of children in higher risk, prior research has been limited by data and application of traditional analysis methods. In this case example focused on Asian American children, we address the gap by applying data-driven statistical and machine learning methods to study clusters of mental health trajectories among children, investigate optimal predictions of children at high-risk cluster, and identify key early predictors. METHODS:Data from the US Early Childhood Longitudinal Study 2010-2011 were used. Multilevel information provided by children, families, teachers, schools, and care-providers were considered as predictors. Unsupervised machine learning algorithm was applied to identify groups of internalizing and externalizing problems trajectories. For prediction of high-risk group, ensemble algorithm, Superlearner, was implemented by combining several supervised machine learning algorithms. Performance of Superlearner and candidate algorithms, including logistic regression, was assessed using discrimination and calibration metrics via crossvalidation. Variable importance measures along with partial dependence plots were utilized to rank and visualize key predictors. FINDINGS/RESULTS:We found two clusters suggesting high- and low-risk groups for both externalizing and internalizing problems trajectories. While Superlearner had overall best discrimination performance, logistic regression had comparable performance for externalizing problems but worse for internalizing problems. Predictions from logistic regression were not well calibrated compared to those from Superlearner, however they were still better than few candidate algorithms. Important predictors identified were combination of test scores, child factors, teacher rated scores, and contextual factors, which showed non-linear associations with predicted probabilities. CONCLUSIONS:We demonstrated the application of data-driven analytical approach to predict mental health outcomes among Asian American children. Findings from the cluster analysis can inform critical age for early intervention, while prediction analysis has potential to inform intervention programing prioritization decisions. However, to better understand external validity, replicability, and value of machine learning in broader mental health research, more studies applying similar analytical approach is needed.

BACKGROUND:In the short term, parental presence while a human infant is in pain buffers the immediate pain responses, although emerging evidence suggests repeated social buffering of pain may have untoward long-term effects. METHODS/FINDING/UNASSIGNED:To explore the short- and long-term impacts of social buffering of pain, we first measured the infant rat pup's [postnatal day (PN) 8, or 12] response to mild tail shock with the mother present compared to shock alone or no shock. Shock with the mother reduced pain-related behavioral activation and USVs of pups at both ages and reduced Fos expression in the periaqueductal gray, hypothalamic paraventricular nucleus, and the amygdala at PN12 only. At PN12, shock with the mother compared to shock alone differentially regulated expression of several hundred genes related to G-protein-coupled receptors (GPCRs) and neural development, whereas PN8 pups showed a less robust and less coherent expression pattern. In a second set of experiments, pups were exposed to daily repeated Shock-mother pairings (or controls) at PN5-9 or PN10-14 (during and after pain sensitive period, respectively) and long-term outcome assessed in adults. Shock+mother pairing at PN5-9 reduced adult carrageenan-induced thermal hyperalgesia and reduced Fos expression, but PN10-14 pairings had minimal impact. The effect of infant treatment on adult affective behavior showed a complex treatment by age dependent effect. Adult social behavior was decreased following Shock+mother pairings at both PN5-9 and PN10-14, whereas shock alone had no effect. Adult fear responses to a predator odor were decreased only by PN10-14 treatment and the infant Shock alone and Shock+mother did not differ. CONCLUSIONS/SIGNIFICANCE/CONCLUSIONS:Overall, integrating these results into our understanding of long-term programming by repeated infant pain experiences, the data suggest that pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone.

IMPORTANCE/OBJECTIVE:Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS:RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION/CONCLUSIONS:RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER/BACKGROUND:Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.