Early Childhood Sleep Intervention in Urban Primary Care: Caregiver and Clinician Perspectives.

BACKGROUND: Despite significant income-related disparities in pediatric sleep, few early childhood sleep interventions have been tailored for or tested with families of lower socio-economic status (SES). This qualitative study assessed caregiver and clinician perspectives to inform adaptation and implementation of evidence-based behavioral sleep interventions in urban primary care with families who are predominantly of lower SES. METHODS: Semi-structured interviews were conducted with (a) 23 caregivers (96% mothers; 83% Black; 65% ≤125% U.S. poverty level) of toddlers and preschoolers with insomnia or insufficient sleep and (b) 22 urban primary care clinicians (physicians, nurse practitioners, social workers, and psychologists; 87% female; 73% White). Guided by the Consolidated Framework for Implementation Research, the interview guide assessed multilevel factors across five domains related to intervention implementation. Qualitative data were analyzed using an integrated approach to identify thematic patterns across participants and domains. RESULTS: Patterns of convergence and divergence in stakeholder perspectives emerged across themes. Participants agreed upon the importance of child sleep and intervention barriers (family work schedules; household and neighborhood factors). Perspectives aligned on intervention (flexibility; collaborative and empowering care) and implementation (caregiver-to-caregiver support and use of technology) facilitators. Clinicians identified many family barriers to treatment engagement, but caregivers perceived few barriers. Clinicians also raised healthcare setting factors that could support (integrated care) or hinder (space and resources) implementation. CONCLUSIONS: Findings point to adaptations to evidence-based early childhood sleep intervention that may be necessary for effective implementation in urban primary care. Such adaptations could potentially reduce significant pediatric sleep-related health disparities.

DNA Methylation Profiles Are Stable in H3 K27M-Mutant Diffuse Midline Glioma Neurosphere Cell Lines.

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but the degree to which such cultures retain the characteristics of the source tumors is unknown. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided a comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

Mapping the development of the basal ganglia in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The basal ganglia are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), but little is known of their development in the disorder. Here, we mapped basal ganglia development from childhood into late adolescence using methods that define surface morphology with an exquisite level of spatial resolution. METHOD: Surface morphology of the basal ganglia was defined from neuroanatomic magnetic resonance images acquired in 270 youth with DSM-IV-defined ADHD and 270 age- and sex-matched typically developing controls; 220 individuals were scanned at least twice. Using linear mixed model regression, we mapped developmental trajectories from age 4 through 19 years at approximately 7,500 surface vertices in the striatum and globus pallidus. RESULTS: In the ventral striatal surfaces, there was a diagnostic difference in developmental trajectories (t = 5.6, p < .0001). Here, the typically developing group showed surface area expansion with age (estimated rate of increase of 0.54 mm(2) per year, standard error [SE] 0.29 mm(2) per year), whereas the ADHD group showed progressive contraction (decrease of 1.75 mm(2) per year, SE 0.28 mm(2) per year). The ADHD group also showed significant, fixed surface area reductions in dorsal striatal regions, which were detected in childhood at study entry and persisted into adolescence. There was no significant association between history of psychostimulant treatment and developmental trajectories. CONCLUSIONS: Progressive, atypical contraction of the ventral striatal surfaces characterizes ADHD, localizing to regions pivotal in reward processing. This contrasts with fixed, nonprogressive contraction of dorsal striatal surfaces in regions that support executive function and motor planning.

Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder.

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in around half of those affected, constituting a major public health challenge. No known demographic, clinical, or neuropsychological factors robustly explain the clinical course, directing our focus to the brain. Herein, we link the trajectories of cerebral cortical development during childhood and adolescence with the severity of adult ADHD. METHODS: Using a longitudinal study design, 92 participants with ADHD had childhood (mean 10.7 years, SD 3.3) and adult clinical assessments (mean 23.8 years, SD 4.3) with repeated neuroanatomic magnetic resonance imaging. Contrast was made against 184 matched typically developing volunteers. RESULTS: Attention-deficit/hyperactivity disorder persisted in 37 (40%) subjects and adult symptom severity was linked to cortical trajectories. Specifically, as the number of adult symptoms increased, particularly inattentive symptoms, so did the rate of cortical thinning in the medial and dorsolateral prefrontal cortex. For each increase of one symptom of adult ADHD, the rate of cortical thinning increased by .0018 mm (SE = .0004, t = 4.2, p < .0001), representing a 5.6% change over the mean rate of thinning for the entire group. These differing trajectories resulted in a convergence toward typical dimensions among those who remitted and a fixed, nonprogressive deficit in persistent ADHD. Notably, cortical thickening or minimal thinning (greater than -.007 mm/year) was found exclusively among individuals who remitted. CONCLUSIONS: Adult ADHD status is linked with the developmental trajectories of cortical components of networks supporting attention, cognitive control, and the default mode network. This informs our understanding of the developmental pathways to adult ADHD.

Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder.

BACKGROUND: Delineation of the cortical anomalies underpinning attention-deficit/hyperactivity disorder (ADHD) can powerfully inform pathophysiological models. We previously found that ADHD is characterized by a delayed maturation of prefrontal cortical thickness. We now ask if this extends to the maturation of cortical surface area and gyrification. METHODS: Two hundred thirty-four children with ADHD and 231 typically developing children participated in the study, with 837 neuroanatomic magnetic resonance images acquired longitudinally. We defined the developmental trajectories of cortical surfaces and gyrification and the sequence of cortical maturation, as indexed by the age at which each cortical vertex attained its peak surface area. RESULTS: In both groups, the maturation of cortical surface area progressed in centripetal waves, both lateral (starting at the central sulcus and frontopolar regions, sweeping toward the mid and superior frontal gyrus) and medial (descending down the medial prefrontal cortex, toward the cingulate gyrus). However, the surface area developmental trajectory was delayed in ADHD. For the right prefrontal cortex, the median age by which 50% of cortical vertices attained peak area was 14.6 years (SE = .03) in ADHD, significantly later than in typically developing group at 12.7 years (SE = .03) [log-rank test χ(¹)² = 1300, p < .00001]. Similar, but less pronounced, delay was found in the left hemispheric lobes. There were no such diagnostic differences in the developmental trajectories of cortical gyrification. CONCLUSIONS: The congruent delay in cortical thickness and surface area direct attention away from processes that selectively affect one cortical component toward mechanisms controlling the maturation of multiple cortical dimensions.