Faculty Bibliography

Fetal inflammation, typically measured indirectly through prenatal maternal cytokine markers, has been shown to impact early childhood executive functions (EFs), which are central to later cognitive and life outcomes. Here, we assessed the impact of prenatal inflammation on EF developmental trajectories using direct placenta histopathology measures in 131 mothers who predominantly self-identified as Black (90.8% Black; 0.8% Asian American, 1.5% biracial, 0.8% Latinx, 3.1% White, 3.1% Missing). We found that placental measures of inflammation were associated with limited gain in EF development from 3 to 5 years old. In follow up analyses, we addressed whether screening questionnaires in infancy might aid in classification of infants as higher risk for subsequent EF problems. We found that parent responses to the Ages & Stages Questionnaire and the Infant/Toddler Sensory Profile at 12 months predict the development of EF abilities in children exposed to chronic inflammation. These findings open promising opportunities for early screening of children at risk for poor executive functioning in children exposed to prenatal inflammation.

BACKGROUND:Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder. METHODS:We searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms. RESULTS:= 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91-1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types. CONCLUSION/CONCLUSIONS:Placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

OBJECTIVE:Real-time imaging is useful for the evaluation of wrist instability. However, currently available real-time magnetic resonance imaging (MRI) methods are limited due to their 2D nature or provide insufficient temporal resolution and image quality for quantitative kinematic analysis. This work introduces a novel approach for volumetric dynamic MRI of the wrist joint during active motion and demonstrates the feasibility of tracking carpal bone motion. MATERIALS AND METHODS/METHODS:A flexible 8-element 3 T wrist receive coil and 3D-printed support platform for guiding motion were designed for dynamic wrist imaging. 2D real-time images were acquired using a fat-saturated FLASH sequence with radial sampling and reconstructed with the GRASP algorithm. Corresponding volumetric dynamic wrist images were obtained by assembling 2D real-time images into 3D snapshots using autodetected MRI-visible markers for slice alignment. The proposed method was demonstrated for radial-ulnar deviation on five healthy volunteers. RESULTS:The flexible wrist coil provided high SNR while allowing a wide range of wrist movements. 2D real-time wrist images were acquired with a temporal resolution of 48 ms/frame with negligible streaking artifacts. Carpal bones and metacarpal bones were properly aligned in the assembled dynamic volumes for all five subjects. The excellent bone-to-tissue contrast enabled accurate segmentation of the individual carpal bones on the assembled dynamic volumes. CONCLUSION/CONCLUSIONS:This work introduces a novel wrist coil and demonstrates that real-time volumetric dynamic examination of the moving wrist is feasible. The achieved image quality and high temporal resolution could enable automatic segmentation of carpal bones and quantitative kinematic assessment for evaluating wrist instability.

BACKGROUND:Spontaneous thought is a universal, complex, and heterogeneous cognitive activity that significantly impacts mental activity and strongly correlates with mental disorders. METHODS:Utilizing the think-aloud method, we captured spontaneous thoughts during rest from 38 diagnosed with depression, alongside 36 healthy controls and 137 healthy individuals. Through a comprehensive assessment of various dimensions of thought content, we compared thought content between individuals with depression and healthy controls, and between healthy women and men. Finally, we employed natural language processing (NLP) to develop regression models for multidimensional content assessment and a classification model to differentiate between individuals with and without depression. RESULTS:Compared to healthy controls, individuals with depression had more internally oriented and less externally oriented spontaneous thoughts. They focused more on themselves and negative things, and less on positive things, experiencing higher levels of negative emotions and lower levels of positive emotions. Besides, we found that compared to healthy men, healthy women's spontaneous thoughts focus more on interoception, the self, past events, and negative events, and they experience higher levels of negative emotions. Meanwhile, we identified the potential application of the think-aloud method to collect spontaneous thoughts and integrate NLP in the field of depression. CONCLUSIONS:This study offers direct insights into the stream of thought during individuals' resting state, revealing differences between individuals with depression and healthy controls, as well as sex differences in the content of spontaneous thoughts. It enhances our understanding of spontaneous thought and offers a new perspective for preventing, diagnosing, and treating depression.

BACKGROUND:Available empirical evidence on participant-level factors associated with dropout from psychotherapies for post-traumatic stress disorder (PTSD) is both limited and inconclusive. More comprehensive understanding of the various factors that contribute to study dropout from cognitive-behavioural therapy with a trauma focus (CBT-TF) is crucial for enhancing treatment outcomes. OBJECTIVE:Using an individual participant data meta-analysis (IPD-MA) design, we examined participant-level predictors of study dropout from CBT-TF interventions for PTSD. METHODS:A comprehensive systematic literature search was undertaken to identify randomised controlled trials comparing CBT-TF with waitlist control, treatment-as-usual or another therapy. Academic databases were screened from conception until 11 January 2021. Eligible interventions were required to be individual and in-person delivered. Participants were considered dropouts if they did not complete the post-treatment assessment. FINDINGS/RESULTS:The systematic literature search identified 81 eligible studies (n=3330). Data were pooled from 25 available CBT-TF studies comprising 823 participants. Overall, 221 (27%) of the 823 dropped out. Of 581 civilians, 133 (23%) dropped out, as did 75 (42%) of 178 military personnel/veterans. Bivariate and multivariate analyses indicated that military personnel/veterans (RR 2.37) had a significantly greater risk of dropout than civilians. Furthermore, the chance of dropping out significantly decreased with advancing age (continuous; RR 0.98). CONCLUSIONS:These findings underscore the risk of premature termination from CBT-TF among younger adults and military veterans/personnel. CLINICAL IMPLICATION/CONCLUSIONS:Understanding predictors can inform the development of retention strategies tailored to at-risk subgroups, enhance engagement, improve adherence and yield better treatment outcomes.

BACKGROUND:Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born <30 weeks of gestational age (GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis. METHODS:We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of infants born <30 weeks of GA. Parents reported on child attention problems at ages 2, 3, 4, and 5 years using the Child Behavior Checklist and the Behavior Assessment System for Children. Sociodemographic and medical characteristics were assessed via maternal interview and medical record review. Neurobehavioral characteristics were determined using neonatal and 2-year assessments. Parent report of child ADHD diagnosis was obtained. We used latent growth curve (LGC) modeling to test our study aims. RESULTS:A linear LGC model provided the best fit to the data. The average trajectory of attention problems evidenced low initial levels of symptoms and little change over time, yet there was significant heterogeneity in both initial levels and change over time. Individual differences in trajectory parameters were associated with sociodemographic, medical, environmental, and neurobehavioral characteristics. Children with higher initial levels of attention problems as well as steeper increases in attention problems over time were more likely to have a reported ADHD diagnosis. CONCLUSIONS:There is significant heterogeneity in trajectories of attention problems from age 2 to 5 in children born <30 weeks of GA and these differences have clinical relevance. These data could inform follow-up guidelines for preterm infants.

To date, sparse attention has been paid to the importance of the "lived experience" of participants and their caregivers in pediatric gene therapy (GT) trials for rare genetic neurological disorders. Pediatric GT studies differ meaningfully from adult GT studies as the decision to participate involves a dyad: the child participant and their caregiver(s). As a multistakeholder group of authors, we are a diverse group with expert perspectives on the social, emotional, physical, and logistical burdens/benefits of trial participation and the myriad ways they affect pediatric GT research. For both pragmatic and ethical reasons, it is essential to prioritize addressing child participant and adult caregiver needs and concerns when designing and conducting GT clinical trials in pediatric populations with rare genetic neurological disorders. We use the term "lived experience" in reference to how people think about and make decisions regarding participation in research studies and how they articulate the emotional, social, ethical, and equity tradeoffs that impact their lives and illness experience. In this article, we describe why accounting for child participants' and adult caregivers' lived experience and addressing pertinent equity issues are essential when designing and conducting pediatric GT trials for rare genetic neurological diseases.

OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development. METHOD/METHODS:We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status. RESULTS:Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001). CONCLUSION/CONCLUSIONS:Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.

In the past decade, there have been substantial changes in diagnostic nomenclature. This study investigated sex differences in attention-deficit/hyperactivity disorder (ADHD) symptom severity based on Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV(TR), and DSM-5 criteria, separating rating scale and clinical interview data in children and adults with ADHD. PubMed, PsycINFO, and Scopus were searched for published studies (1996-2021) reporting severity of attention, and hyperactivity/impulsivity in males and females. We compared data: (1) across the entire lifespan aggregating rating scale and clinical interview data (51 studies), (2) drawing solely on rating scale data (18 studies), and (3) drawing solely on clinical interview data (33 studies). Fifty-two studies met inclusion criteria comparing data for females (n = 8423) and males (n = 9985) with ADHD across childhood and/or adulthood. In total, 15 meta-analyses were conducted. Pooled data across the lifespan aggregating both rating scale and clinical diagnostic interview data, showed males had significantly more severe hyperactivity/impulsivity symptoms than females. Rating scale data were similar; boys had significantly more severe hyperactivity/impulsivity than girls. In adulthood, men were rated to have significantly more severe inattention than women with no difference in the hyperactivity/impulsivity dimension. All significant differences were of small effect size. No significant sex differences in the severity of symptoms emerged for clinical interview data for children or adults, in contrast. Possible reasons for the discrepancy in findings between rating scales and clinical diagnostic interviews are discussed.

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.