Faculty Bibliography

OBJECTIVES/OBJECTIVE:Adolescents living with HIV (ALHIV) have low viral suppression levels, with 1 in 3 ALHIV experiencing virologic failure, calling for more efforts to reverse these trends. We developed and validated a model that predicts the risk of virologic failure (VF) among ALHIV. STUDY DESIGN/METHODS:Cross-sectional study. METHODS:We used baseline data from 702 ALHIV enrolled in the Suubi + Adherence cluster-randomized clinical trial. Participants were aged 10-16 years, living with HIV and aware of their HIV status, and are living with a family. We developed a risk-prediction model for VF (viral load of ≥200 copies/mL) using sociodemographic, behavioral, psychological, economic, and treatment-related factors. LASSO logistic regression using 10-fold cross-validation with bootstrapping was used to select the predictors for the final model. Model performance was assessed by determining the discrimination using the area under the curve and calibration by drawing a calibration plot. RESULTS:Using a lambda value of 0.007, the final model had 24 predictors (and interaction terms). The predictors included the participants' age, sex, work status, stigma, depressive symptoms, adherence self-efficacy, HIV knowledge, duration with HIV, time spent on ART, communication with the caregiver, family cohesion, social support, orphanhood status, number of people in the household, HIV disclosure, years spent at the current residence, and household asset ownership. The model predicted VF with AUC of 73.8 (95 % CI: 68.3-78.0) and calibration slope of 0.985. CONCLUSIONS:We developed and validated a model to predict the risk of virologic failure among ALHIV in Uganda, demonstrating its potential utility in identifying individuals at elevated risk for VF. Future models could be refined by incorporating clinical characteristics such as CD4 count to further improve predictive accuracy.

While studies have documented neural correlates of language delay in toddlers with developmental conditions, those at genetic risk for language delay, and those born premature, no studies have examined neural correlates in toddlers exhibiting early language delay without known etiology. This study examines brain morphometry in toddlers with and without early language delay. To do so, we collected magnetic resonance imaging on toddlers with language delay (LD; n=7, M_age=19.67 months, 3 female, 2 Hispanic, 4 non-caucasian) and a typically developing (TD; n=17, M_age=22.73 months, 8 female, 2 Hispanic, 3 non-caucasian) comparison group. Exploratory analyses examined group differences in total brain volume, cortical thickness, and cortical surface area using both a whole-brain and region of interest (Broca's and Wernicke's areas) approach. Results showed no gross brain anatomical differences between groups. However, there were group differences in cortical surface area in the temporal cortex (including Wernicke's area and left middle temporal gyrus, hedges' g= -.35) and Broca's area thickness. Results are reported using multiple analytic methods, age matching, and exclusion of children later diagnosed with autism. While this exploratory study has a limited sample size, it provides novel findings that can be utilized to guide hypothesis-driven imaging studies on toddler language delay.

OBJECTIVE/UNASSIGNED:We used resting-state functional magnetic resonance imaging to identify changes in brain functional connectivity (FC) associated with Organizational Skills Training (OST). METHOD/UNASSIGNED:In an open, waitlist-controlled, randomized clinical trial (NCT04108273), 51 children aged 8-12 years with deficient organizational skills were assigned to immediate tele-health OST treatment (twice weekly, 10 weeks) or waitlist. We obtained Children's Organizational Skills Scale-Parent version (COSS-P) scores and examined FC changes between dorsal anterior cingulate cortex (dACC) and preregistered subcortical anterior ventral striatum (aVS) regions-of-interest. RESULTS/UNASSIGNED: < 0.05). Analyses were then performed with two additional analytic pipelines, neither of which detected any significant effects. CONCLUSION/UNASSIGNED:Although improvements in organizational deficits were associated with increased FC within a circuit linking dACC and the default mode network region of the aVS in one analysis, the direction was the opposite of predicted and results did not replicate. Thus, we highlight the tentativeness of our findings; we have de-identified all the data and made it available for investigators to examine and to combine with other datasets in mega- and meta-analyses. Future studies should also include alternative control conditions and larger samples. CLINICAL TRIAL REGISTRATION/UNASSIGNED:https://clinicaltrials.gov/study/NCT04108273?cond=NCT04108273&rank=1.

BACKGROUND/UNASSIGNED:Although historical writings, anthropological accounts, and experimental studies document associations between psilocybin use and religion, no prospective experimental study has investigated how the effects of psilocybin are experienced and interpreted by religious clergy. This exploratory study evaluated the overall safety and the acute and enduring effects of psilocybin in clergy. METHODS/UNASSIGNED:= 16) at 6 months after screening using self-report measures. The effects of psilocybin were also assessed on session days and 4 and 16 months after the second psilocybin session in the 24 participants who completed both sessions. RESULTS/UNASSIGNED:The primary outcome assessment at 6 months after screening showed that, compared with the delayed control group, participants who had received psilocybin reported significantly greater positive changes in their religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in their non-religious attitudes, moods, and behavior. Follow-up assessments showed that positive changes in religious and non-religious attitudes and behavior were sustained through 16 months after the second psilocybin session. At that time, participants rated at least one of their psilocybin experiences to be among the top five most spiritually significant (96%), profoundly sacred (92%), psychologically insightful (83%), and psychologically meaningful (79%) of their lives. Furthermore, 42% rated one of their experiences to be the single most profound of their lifetime. At 16-months follow-up, most (79%) strongly endorsed that the experiences had positive effects on their religious practices (e.g., prayer or meditation) and their daily sense of the sacred, and most (71%) reported positive changes in their appreciation of religious traditions other than their own. Although no serious adverse events were reported, 46% rated a psilocybin experience as among the top five most psychologically challenging of their lives. CONCLUSIONS/UNASSIGNED:In this population of clergy, psilocybin administration was safe and increased multiple domains of overall psychological well-being including positive changes in religious attitudes and behavior as well as their vocation as a religious leader. The study was limited by a waitlist control design, homogenous sample, and the use of some unvalidated outcome measures. Further research with more rigorous control conditions and diverse samples is needed.

Allostatic load provides a valuable framework for examining how cumulative stress impacts multiple physiological systems simultaneously, making it a powerful tool for understanding the mechanisms through which stress contributes to adverse pregnancy outcomes. This multisystem perspective is especially important during pregnancy, a period characterized by heightened vulnerability to stress and significant physiological changes that can themselves contribute to allostatic load. Although the impact of allostatic load during pregnancy is well documented, the mechanisms and moderators involved by trimester remain unclear, particularly given wide variation in social, cultural, and structural determinants of maternal health worldwide. In this review, we discuss the progress that has been made over the past two decades in studying prenatal allostatic load and describe the clinical implications of this by highlighting sensitive periods of interest throughout gestation. Despite these advances, key questions remain regarding the intergenerational transmission of risk, the specificity of findings to the pregnancy period, and the role of factors that often accompany elevated allostatic load, such as poor sleep, limited social support, systemic inequities, and comorbid mental or physical health conditions, which may manifest differently across global contexts. Most existing studies have been conducted in high-income settings, yet the burden of adverse pregnancy outcomes is greatest in low- and middle-income countries, where structural, environmental, and social stressors are pervasive. Expanding this framework to include diverse global contexts is essential for understanding how social inequities and chronic stressors shape maternal physiology worldwide. We discuss these issues and offer directions for future research, including the goal of developing a standardized metric for measuring allostatic load - one that we believe will advance the field's understanding of how prenatal allostatic load markers by trimester relate to maternal and infant outcomes.

A fundamental pillar of science is the estimation of the effect size of associations. However, this task is sometimes difficult and error-prone. To facilitate this process, the R package metaConvert automatically calculates and flexibly converts multiple effect size measures. It applies more than 120 formulas to convert any relevant input data into Cohen's d, Hedges' g, mean difference, odds ratio, risk ratio, incidence rate ratio, correlation coefficient, Fisher's r-to-z transformed correlation coefficient, variability ratio, coefficient of variation ratio, or number needed to treat. Researchers unfamiliar with R can use this software through a browser-based graphical interface (https://metaconvert.org/). We hope this suite will help researchers in the life sciences and other disciplines estimate and convert effect sizes more easily and accurately.

BACKGROUND:Freezing of gait (FOG) is a common gait disorder that often accompanies Parkinson's disease (PD). The current understanding of brain functional organization in FOG was built on the assumption that the functional connectivity (FC) of networks is static, but FC changes dynamically over time. We aimed to characterize the dynamic functional connectivity (DFC) in patients with FOG based on high temporal-resolution functional MRI (fMRI). METHODS:Eighty-seven PD patients, including 29 with FOG and 58 without FOG, and 32 healthy controls underwent resting-state fMRI. Spatial independent component analysis and a sliding-window approach were used to estimate DFC. RESULTS:Four patterns of structured FC 'states' were identified: a frequent and sparsely connected network (State I), a less frequent but highly synchronized network (State IV), and two states with opposite connecting directions between the visual network and the sensorimotor network (positively connected in State II, negatively connected in State III). Compared with the non-FOG group, patients with FOG spent significantly less time in State II and more time in State III. The longer dwell time in State III was correlated with more severe FOG symptoms. The fractional window of State III tended to correlate to visual-spatial and executive dysfunction in FOG. Moreover, fewer transitions between brain states and lower variability in local efficiency were observed in FOG, suggesting a relatively 'rigid' brain. CONCLUSIONS:This study highlights how visuomotor network dynamics are related to the presence and severity of FOG in PD patients, which provides new insights into understanding the pathophysiological mechanisms that underly FOG. © 2025 International Parkinson and Movement Disorder Society.

BACKGROUND:To progress adolescent mental health research beyond our present achievements-a complex account of brain and environmental risk factors without understanding neurobiological embedding in the environment-we need methods to uncover relationships between the developing brain and real-world environmental experiences. METHODS:We investigated associations between brain function, environments, and emotional and behavioral problems using participants from the Adolescent Brain Cognitive Development (ABCD) Study (n = 2401 female). We applied manifold learning, a promising technique for uncovering latent structure from high-dimensional biomedical data such as functional magnetic resonance imaging. Specifically, we developed exogenous PHATE (potential of heat-diffusion for affinity-based trajectory embedding) (E-PHATE) to model brain-environment interactions. We used E-PHATE embeddings of participants' brain activation during emotional and cognitive processing tasks to predict individual differences in cognition and emotional and behavioral problems both cross-sectionally and longitudinally. RESULTS:E-PHATE embeddings of participants' brain activation and environments at baseline showed moderate-to-large associations with total, externalizing, and internalizing problems at baseline, across several subcortical regions and large-scale cortical networks, compared with the zero-to-small effects achieved by voxelwise data or common low-dimensional embedding methods. E-PHATE embeddings of the brain and environment at baseline were also related to emotional and behavioral problems 2 years later. These longitudinal predictions showed a consistent moderate effect in the frontoparietal and attention networks. CONCLUSIONS:The embedding of the adolescent brain in the environment yields enriched insight into emotional and behavioral problems. Using E-PHATE, we demonstrated how the harmonization of cutting-edge computational methods with longstanding developmental theories advances the detection and prediction of adolescent emotional and behavioral problems.

Firesetting behaviors are extremely dangerous not only to the individual but to society as one fire has the potential to destroy property and lead to serious injury or death. Youth firesetting behaviors are often under-assessed in psychiatric care settings intakes due to their relatively low base-rate and only are a part of a practitioner’s conceptualization when these behaviors are part of their presentation to an emergency room. Acute psychiatric care settings are well-equipped to assess and treat many highly dangerous behaviors such as active suicidal and homicidal ideation, as well as non-suicidal self-injury. However, youth firesetting is without a formal and directed plan on how to assess the risk of these behaviors, conceptualize, and intervene effectively. A case study of a 16-year-old multiracial male named “Luis”, who was psychiatrically hospitalized on an adolescent inpatient unit following multiple firesetting behaviors in the community, is used is to show the importance of multiinterdisciplinary collaboration between mental health providers and local fire safety programs. In addition, we will offer several recommendations to providers in the assessment and treatment related to juvenile who fireset