Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD. METHODS:This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic). RESULTS:Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day. CONCLUSIONS:Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment. CLINICAL TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT04143217.

Existential distress is commonly experienced by patients diagnosed with a life-threatening illness. This condition has been shown to adversely impact quality of life and is correlated with increased suicidal ideation and requests for hastened death. While palliative care teams are experienced in treating depression and anxiety, existential distress is a distinct clinical condition for which traditional medications and psychotherapy approaches demonstrate limited efficacy or duration of effect. Psychedelic drugs, including psilocybin and lysergic acid diethylamide (LSD), in conjunction with psychotherapy have been shown to produce rapid and sustained reductions in existential and psychiatric distress and may be a promising treatment for patients facing existential distress in palliative care settings. In this narrative review article, we describe the history of psychedelic medicine including early studies and the modern wave of research over the past 20 years, which includes high quality clinical trial data. This review outlines specific considerations for therapeutic application of psilocybin including pharmacokinetics, patient selection, dosing, protocol designs, and safeguards to reduce potential adverse effects to help guide future psychedelic practitioners. With growing public interest and evolving state level policy reforms allowing access to psychedelic treatments, it is critical for palliative care providers to gain familiarity with the current state of science and the potential of psilocybin assisted psychotherapy in the treatment of existential distress.

PURPOSE/OBJECTIVE:Stronger Together is a peer mentoring model that seeks to address the severe lack of mental health and psychosocial support for patients with cancer in many low- and middle-income countries (LMICs). This article presents the results of the Stronger Together pilot study among patients with breast and gynecologic cancer in Viet Nam (VN). METHODS:Eligible participants comprised women age 25 years or older with a diagnosis of breast or gynecologic cancers and receiving treatment at four participating hospitals. Participants were asked whether they wanted to proceed with usual care or be matched with a trained and supervised peer mentor (a cancer survivor). Surveys were administered at baseline (0) and 2, 4, and 6 months and assessed depression, anxiety, stress, mental health and physical health components of quality of life (QOL), self-efficacy, and social support. We computed and compared 2-, 4-, and 6-month changes in scores from baseline and conducted difference-in-difference analyses to estimate the intervention effect at 6 months. RESULTS:The sample size included N = 186 participants. Mentees (n = 91) exhibited improvements in depression, anxiety, stress, and mental health QOL across all time points, whereas usual care participants (n = 95) experienced these improvements at later periods (4 and 6 months). Compared with usual care participants, mentees reported greater improvements in depression at 2 and 4 months, mental health QOL at all time points, and self-efficacy and social support at 4 and 6 months. Greater improvements in stress were also seen in the breast cancer subsample. CONCLUSION/CONCLUSIONS:Stronger Together is a promising model to improve mental health and psychosocial outcomes among patients with breast and gynecologic cancer in VN and can help fill gaps in cancer peer support interventions in many LMICs.

Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions (n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Researchers in ubiquitous computing have long promised that passive sensing will revolutionize mental health measurement by detecting individuals in a population experiencing a mental health disorder or specific symptoms. Recent work suggests that detection tools do not generalize well when trained and tested in more heterogeneous samples. In this work, we contribute a narrative review and findings from two studies with 41 mental health clinicians to understand these generalization challenges. Our findings motivate research on actionable sensing, as an alternative to detection research, studying how passive sensing can augment traditional mental health measures to support actions in clinical care. Specifically, we identify how passive sensing can support clinical actions by revealing patients' presenting problems for treatment and identifying targets for behavior change and symptom reduction, but passive data requires additional contextual information to be appropriately interpreted and used in care. We conclude by suggesting research at the intersection of actionable sensing and mental healthcare, to align technical research in ubiquitous computing with clinical actions and needs.

BACKGROUND:Climate change has adverse effects on youth mental health and wellbeing, but limited large-scale data exist globally or in the USA. Understanding the patterns and consequences of climate-related distress among US youth can inform necessary responses at the individual, community, and policy level. METHODS:A cross-sectional descriptive online survey was done of US youth aged 16-25 years from all 50 states and Washington, DC, between July 20 and Nov 7, 2023, via the Cint digital survey marketplace. The survey assessed: climate-related emotions and thoughts, including indicators of mental health; relational aspects of climate-related emotions; beliefs about who or what has responsibility for causing and responding to climate change; desired and planned actions in response to climate change; and emotions and thoughts about the US Government response to climate change. Respondents were asked whether they had been affected by various severe weather events linked to climate change and for their political party identification. Sample percentages were weighted according to 2022 US census age, sex, and race estimates. To test the effects of political party identification and self-reported exposure to severe weather events on climate-related thoughts and beliefs we used linear and logistic regression models, which included terms for political party identification, the number of self-reported severe weather event types in respondents' area of residence in the past year, and demographic control variables. FINDINGS/RESULTS:We evaluated survey responses from 15 793 individuals (weighted proportions: 80·5% aged 18-25 years and 19·5% aged 16-17 years; 48·8% female and 51·2% male). Overall, 85·0% of respondents endorsed being at least moderately worried, and 57·9% very or extremely worried, about climate change and its impacts on people and the planet. 42·8% indicated an impact of climate change on self-reported mental health, and 38·3% indicated that their feelings about climate change negatively affect their daily life. Respondents reported negative thoughts about the future due to climate change and actions planned in response, including being likely to vote for political candidates who support aggressive climate policy (72·8%). In regression models, self-reported exposure to more types of severe weather events was significantly associated with stronger endorsement of climate-related distress and desire and plans for action. Political party identification as Democrat or as Independent or Other (vs Republican) was also significantly associated with stronger endorsement of distress and desire and plans for action, although a majority of self-identified Republicans reported at least moderate distress. For all survey outcomes assessed in the models, the effect of experiencing more types of severe weather events did not significantly differ by political party identification. INTERPRETATION/CONCLUSIONS:Climate change is causing widespread distress among US youth and affecting their beliefs and plans for the future. These effects may intensify, across the political spectrum, as exposure to climate-related severe weather events increases. FUNDING/BACKGROUND:Avaaz Foundation.

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

Recent studies using the diffusion decision model find that performance across many cognitive control tasks can be largely attributed to a task-general efficiency of evidence accumulation (EEA) factor that reflects individuals' ability to selectively gather evidence relevant to task goals. However, estimates of EEA from an n-back "conflict recognition" paradigm in the Adolescent Brain Cognitive Development^SM (ABCD) Study, a large, diverse sample of youth, appear to contradict these findings. EEA estimates from "lure" trials-which present stimuli that are familiar (i.e., presented previously) but do not meet formal criteria for being a target-show inconsistent relations with EEA estimates from other trials and display atypical v-shaped bivariate distributions, suggesting many individuals are responding based largely on stimulus familiarity rather than goal-relevant stimulus features. We present a new formal model of evidence integration in conflict recognition tasks that distinguishes individuals' EEA for goal-relevant evidence from their use of goal-irrelevant familiarity. We then investigate developmental, cognitive, and clinical correlates of these novel parameters. Parameters for EEA and goal-irrelevant familiarity-based processing showed strong correlations across levels of n-back load, suggesting they are task-general dimensions that influence individuals' performance regardless of working memory demands. Only EEA showed large, robust developmental differences in the ABCD sample and an independent age-diverse sample. EEA also exhibited higher test-retest reliability and uniquely meaningful associations with clinically relevant dimensions. These findings establish a principled modeling framework for characterizing conflict recognition mechanisms and have several broader implications for research on individual and developmental differences in cognitive control.