Scott H. Kollins’s research while affiliated with Duke University and other places

Background: Digitization (using novel digital tools and strategies) and consumerism (taking a consumer-oriented approach) are increasingly commonplace in clinical trials, but the implications of these changes are not well described. Methods: We assembled a group of trial experts from academia, industry, non-profit, and government to discuss implications of this changing trial landscape and provide guidance. Results: Digitization and consumerism can increase the volume and diversity of trial participants and expedite recruitment. However, downstream bottlenecks, challenges with retention, and serious issues with equity, ethics, and security can result. A "click and mortar" approach, combining approaches from novel and traditional trials with the thoughtful use of technology, may optimally balance opportunities and challenges facing many trials. Conclusion: We offer expert guidance and three "click and mortar" approaches to digital, consumer-oriented trials. More guidance and research are needed to navigate the associated opportunities and challenges.

Introduction Sleep complaints are prevalent and impairing symptoms among adolescents with ADHD. Our recent work has shown that key aspects of sleep physiology differentiate adolescents with ADHD from healthy controls (HC), including reduced slow-wave sleep percentage (SWS%) and relative delta power (rDelta) and increased stage 2 percentage (N2%) and relative sigma power (rSigma) after accounting for sleep duration. ADHD-related sleep problems may emerge as early as toddlerhood, yet little is known about the trajectory of sleep disturbances over time in ADHD. The current study examines relationships between early childhood sleep problems and adolescent sleep physiology in ADHD and HC. Methods Sixty-two medication-free adolescents (31 with ADHD, mean age=15.3, 50% female) completed a diagnostic interview (Mini International Neuropsychiatric Interview) and 3 nights of at-home polysomnography. Spectral analysis was conducted on a single O1-C3 channel. Caregivers reported on participants’ sleep problems during toddlerhood and preschool (Child Behavior Questionnaire; CBQ). Linear regressions controlling for age, sex, and pubertal status examined relationships between early childhood sleep problems and aspects of sleep physiology implicated in adolescent ADHD (SWS%, rDelta, N2%, rSigma) and whether associations differed between groups. Results Adolescents with ADHD had greater caregiver-reported early childhood sleep problems compared to HC (t(60)=3.71, p<.001). In the full sample, greater caregiver-reported sleep problems in early childhood were associated with reduced SWS% (β=-.28, p=.04) and rDelta (β=-.27, p=.04), and increased rSigma (β=.33, p=.02), in adolescence. An early childhood sleep by group interaction was observed for rDelta (β=1.09, p=.04), such that the association was significantly stronger for adolescents with ADHD than HC. Conclusion The current study found that sleep problems in early development were associated with disruptions in sleep physiology in adolescents, including relatively less time spent in SWS, reduced delta power, and increased sigma power. Results suggest that ADHD-related sleep problems may begin early in life and persist into adolescence. Screening for and treating sleep problems during early development may be important for supporting sleep health among adolescents with ADHD, and future studies should assess this possibility. Future studies employing longitudinal designs may clarify the contribution of sleep disturbances to the onset and persistence of ADHD symptoms across development. Support (if any) K23MH108704; R34MH128440

Attention-deficit/hyperactivity disorder (ADHD) symptoms affect 40-60% of autistic children and have been linked to differences in adaptive behavior. It is unclear whether adaptive behavior in autistic youth is directly impacted by co-occurring ADHD symptoms or by another associated feature of both autism and ADHD, such as increased irritability. The current study examined relationships between irritability, ADHD symptoms, and adaptive behavior in 3- to 7-year-old autistic children. Results suggest that, after adjusting for co-occurring ADHD symptoms, higher levels of irritability are associated with differences in social adaptive behavior specifically. Understanding relationships between irritability, ADHD, and adaptive behavior in autistic children is critical because measures of adaptive behavior, such as the Vineland Scales of Adaptive Functioning, are often used as a proxy for global functioning, as well as for developing intervention plans and measuring outcomes as primary endpoints in clinical trials.

Background/Objectives Sleep measures, such as duration and onset timing, are associated with adiposity outcomes among children. Recent research among adults has considered variability in sleep and wake onset times, with the Sleep Regularity Index (SRI) as a comprehensive metric to measure shifts in sleep and wake onset times between days. However, little research has examined regularity and adiposity outcomes among children. This study examined the associations of three sleep measures (i.e., sleep duration, sleep onset time, and SRI) with three measures of adiposity (i.e., body mass index [BMI], waist circumference, and waist-to-height ratio [WHtR]) in a pediatric sample. Subjects/Methods Children (ages 4–13 years) who were part of the U.S. Newborn Epigenetic STudy (NEST) participated. Children (N = 144) wore an ActiGraph for 1 week. Sleep measures were estimated from actigraphy data. Weight, height, and waist circumference were measured by trained researchers. BMI and WHtR was calculated with the objectively measured waist and height values. Multiple linear regression models examined associations between child sleep and adiposity outcomes, controlling for race/ethnicity, child sex, age, mothers’ BMI and sleep duration. Results When considering sleep onset timing and duration, along with demographic covariates, sleep onset timing was not significantly associated with any of the three adiposity measures, but a longer duration was significantly associated with a lower BMI Z-score (β = −0.29, p < 0.001), waist circumference (β = −0.31, p < 0.001), and WHtR (β = −0.38, p < 0.001). When considering SRI and duration, duration remained significantly associated with the adiposity measures. The SRI and adiposity associations were in the expected direction, but were non-significant, except the SRI and WHtR association (β = −0.16, p = 0.077) was marginally non-significant. Conclusions Sleep duration was consistently associated with adiposity measures in children 4–13 years of age. Pediatric sleep interventions should focus first on elongating nighttime sleep duration, and examine if this improves child adiposity outcomes.

Introduction Sleep disturbances are common among adolescents with ADHD; however, few studies have characterized the nature of ADHD-related sleep problems using the gold-standard sleep measure, polysomnography (PSG), in adolescence. Additionally, although similar cognitive deficits are common across ADHD and sleep-disordered populations, the potential role of sleep in contributing to cognitive impairment in adolescent ADHD is unknown. This study investigates differences in PSG-measured sleep among adolescents with ADHD versus healthy controls without psychiatric disorders (HC) and associations with cognition. Methods Sixty-two adolescents aged 13-17 (31 ADHD, mean age=15.3, 50% female) completed a psychiatric evaluation and 3 nights of ambulatory PSG. Following the third night, participants completed the Cambridge Neuropsychological Test Automated Battery (CANTAB). Sleep variables were averaged over 3 nights. Linear regressions controlling for age and sex examined group differences in a range of traditional PSG and spectral EEG indices as well as relationships between PSG/spectral indices and cognition (two summary scores derived from CANTAB: response accuracy and response time) within the ADHD group. Results Adolescents with ADHD displayed reduced SWS% (F(3,51)=9.67, p=.003), increased N2% (F(3,51)=10.35, p=.002), increased relative sigma (F(3,47)=6.55, p=.01) and beta (F(3,47)=4.10, p<.05) power, and a trend toward reduced relative delta power (F(3,47)=2.95, p=.09) compared to HC. Within the ADHD group, greater REM% (r=.43), reduced N2% (r=-.55), greater relative delta power (r=.52), higher delta power peak (r=.56), steeper delta decline overnight (r=-.56), and reduced relative theta (r=-.53), beta (r=-.74), and gamma (r=-.67) power were associated with better response accuracy (p’s<.05). Greater relative delta (r=-.51), and reduced relative theta (r=.55) and beta (r=.63), power were associated with faster response times. Conclusion Although adolescents with ADHD did not differ from HC on traditional PSG measures (TST, WASO), they exhibited abnormalities in sleep stage distribution and non-REM EEG frequency spectral indices, including reduced SWS and low frequency power and increased stage 2 sleep and high frequency power overnight. Notably, similar parameters were associated with impaired cognition, suggesting sleep may contribute to cognitive deficits in ADHD. Future studies may clarify whether sleep plays a causal role in cognitive impairments in adolescent ADHD and if sleep treatments result in improved cognition in this population. Support (If Any) K23MH108704

As children age, they can learn increasingly complex features of environmental structure—a key prerequisite for adaptive decision-making. Yet when we tested children ( N = 304, 4–13 years old) in the Children’s Gambling Task, an age-appropriate variant of the Iowa Gambling Task, we found that age was negatively associated with performance. However, this paradoxical effect of age was found only in children who exhibited a maladaptive deplete-replenish bias, a tendency to shift choices after positive outcomes and repeat choices after negative outcomes. We found that this bias results from sensitivity to incidental nonrandom structure in the canonical, deterministic forms of these tasks—and that it would actually lead to optimal outcomes if the tasks were not deterministic. Our results illustrate that changes in decision-making across early childhood reflect, in part, increasing sensitivity to environmental structure.

When COVID-19 disrupted autism spectrum disorder research globally, many clinical trials of behavioral interventions pivoted to telehealth. Telehealth has the potential to increase geographic reach and improve racial/ethnic diversity in research. This matters because most autism spectrum disorder intervention studies have primarily included White, upper-middle-income families from North America and Europe. Participant homogeneity limits our ability to identify what types of intervention works in which context for which populations. Importantly, telehealth needs to “fit” the local context, and in particular, include strategies that factor in the “digital divide.” This short report details contextual considerations and pre-implementation pragmatic adaptations in two autism spectrum disorder clinical trials that include Early Start Denver Model–informed caregiver coaching in the United States and South Africa. By comparing and contrasting how implementation context informed the telehealth pivot in these two clinical trials in different hemispheres, we highlight equity considerations for adaption. The pandemic is an opportunity to understand how remote intervention can “fit” diverse contexts, while providing valid scientific results. It is however important that adaptations be documented and feasibility of the adapted approach be tracked. COVID-19-related telehealth adaptations of behavioral interventions could facilitate the development of new strategies with wider global impact. Lay abstract COVID-19 caused many autism spectrum disorder caregiver-coaching studies to move to telehealth. Telehealth can increase the diversity of people who take part in research. This matters because most autism spectrum disorder studies have included people who have resources, are White, and live in North America and Europe. When study participants are similar, it is hard to understand which interventions can help different types of people who live in different parts of the world. While telehealth may allow more people to take part in research, it needs to “fit” the local context and consider the “digital divide” because many people around the world have no access to computers and the Internet. This short report describes changes to two research studies that include caregiver coaching based on the Early Start Denver Model in the United States and South Africa. We describe how the local context, including technology and Internet access, guided the telehealth approach. By doing so, we highlight ways to make telehealth available to more people around the world. The pandemic can help us understand how telehealth can “fit” diverse places and support high-quality research. It is important that study changes are tracked and we assess how well the changes work. COVID-19 telehealth changes to caregiver coaching can result in new ways to reach more people around the world.

Objective Eveningness diurnal preference is common in psychiatric conditions, including attention-deficit/hyperactivity disorder (ADHD) and internalizing disorders. Little is known about how diurnal preference relates to sluggish cognitive tempo (SCT)—a distinct clinical construct associated with functional impairment—in clinical samples. Method Adult outpatients (n = 65; 43 with ADHD, 22 with internalizing/adjustment disorders) self-reported on SCT symptoms (total symptoms; slow/daydreamy, sleepy/sluggish, and low initiation/persistence factors) and diurnal preference. Results Greater eveningness was associated with overall SCT severity and sleepy/sluggish symptoms in the full sample. Relationships between eveningness and overall SCT severity and slow/daydreamy symptoms were stronger for those with internalizing/adjustment disorders compared to ADHD. The relationship between eveningness and sleepy/sluggish symptoms was uniform across groups. Conclusion Findings suggest a potential role of eveningness preference in adult SCT presentation. Future studies should investigate underlying mechanisms linking these two constructs and the efficacy of circadian interventions in the treatment of SCT among adult outpatients.

STARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8–14-year-old children with attention-deficit/hyperactivity disorder (ADHD) on stimulant medication ( n = 130) or not on any ADHD medication ( n = 76). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale—Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: −0.7, p < 0.001; No Stimulants: −0.5, p < 0.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01’s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.

Study objectives: Caffeine use is ubiquitous among adolescents and may be harmful to sleep, with downstream implications for health and development. Research has been limited by self-reported and/or aggregated measures of sleep and caffeine collected at a single time point. This study examines bidirectional associations between daily caffeine consumption and electroencephalogram-measured sleep among adolescents and explores whether these relationships depend on timing of caffeine use. Methods: Ninety-eight adolescents aged 11-17 (M=14.38, SD=1.77; 50% female) participated in 7 consecutive nights of at-home sleep electroencephalography and completed a daily diary querying morning, afternoon, and evening caffeine use. Linear mixed effects regressions examined relationships between caffeine consumption and total sleep time, sleep-onset latency, sleep efficiency, wake after sleep onset, and time spent in sleep stages. Impact of sleep indices on next-day caffeine use was also examined. Results: Increased total caffeine consumption was associated was increased sleep-onset latency (β=.13; 95% CI=.06,.21; p<.001) and reduced total sleep time (β=-.17; 95% CI=-.31,-.02; p=.02), sleep efficiency (β=-1.59; 95% CI=-2.51,-.67, p<.001), and rapid-eye movement sleep (β=-.12; 95% CI=-.19,-.05; p<.001). Findings were driven by afternoon and evening caffeine consumption. Reduced sleep efficiency was associated with increased afternoon caffeine intake the following day (β=-.006; 95% CI=-.012,-.001; p=.01). Conclusions: Caffeine consumption, especially afternoon and evening use, impacts several aspects of adolescent sleep health. In contrast, most sleep indicators did not affect next-day caffeine use, suggesting multiple drivers of adolescent caffeine consumption. Federal mandates requiring caffeine content labeling and behavioral interventions focused on reducing caffeine intake may support adolescent sleep health.