Faculty Bibliography

The Child Behavior Checklist (CBCL) is a widely used parent-report of child and adolescent behavior. We examined the ability of the CBCL-A scale, a previously published subset of CBCL items, to predict the presence of generalized anxiety disorder (GAD), separation anxiety disorder (SAD), and social phobia (SoP), as well as anxiety severity, among 488 youth randomized in the Child Anxiety Multimodal Study (CAMS). We predicted that the CBCL-A's unique inclusion of items related to somatic symptoms would better identify anxiety disorder and severity than other CBCL scales, given that somatic complaints are often key features of anxiety among youth. Results support the use of the anxiety-based CBCL subscales as first-line screeners for generally elevated symptoms of anxiety, rather than tools to identify specific anxiety disorders. Although somatic symptoms are often reported and included in diagnostic criteria for certain anxiety disorders (e.g., SAD, GAD), the unique combination of somatic and non-somatic symptoms for the CBCL-A subscale did not increase its ability to consistently predict the presence of specific anxiety disorders.

Over the past decades studies of the neurobiology of memory were largely restricted to consideration of cellular and molecular events taking place immediately or shortly after training, the so-called consolidation period. More recent views have recognized that the memory process includes sensory processing, orienting of attention, retrieval, encoding, and subsequent consolidation. Advances in biotechnology are providing new tools to gain insights at every level of the memory process. New data from experiments employing high definition fMRI are confirming the role of the Locus Coeruleus (LC) noradrenergic system in reorienting of attention and in cognitive flexibility. Electrophysiological studies show new task-related activation of these neurons and learning-related off line activation and suggest a temporal relationship between LC spiking and cortical oscillations in the theta and gamma frequencies.

OBJECTIVE: Recent data suggest that both disordered sleep and low serum iron occur more frequently in children with autism compared with children with typical development. Iron deficiency has been linked to specific sleep disorders. The goal of the current study was to evaluate periodic limb movements in sleep and iron status in a group of children with autism compared with typically developing children and children with nonautism developmental delay to determine if iron status correlated with polysomnographic measures of latency and continuity and periodic limb movements in sleep. METHODS: A total of 102 children (68 with autism, 18 typically developing, 16 with developmental delay) aged 2 to 7 years underwent a one-night modified polysomnography study and phlebotomy at the National Institutes of Health to measure serum markers of iron status (ferritin, iron, transferrin, percent transferrin saturation). RESULTS: No serum iron marker was associated with periodic limb movements of sleep or any other sleep parameter; this did not differ among the diagnostic groups. No significant differences among groups were observed on serum iron markers or most polysomnogram parameters: periodic limb movements in sleep, periodic limb movements index, wake after sleep onset, or sleep efficiency. Children in the autism group had significantly less total sleep time. Serum ferritin was uniformly low across groups. CONCLUSIONS: This study found no evidence that serum ferritin is associated with polysomnogram measures of latency or sleep continuity or that young children with autism are at increased risk for higher periodic limb movements index compared with typically developing and developmental delay peers.

Working memory (WM) is central to the acquisition of knowledge and skills throughout childhood and adolescence. While numerous behavioral and task-based functional magnetic resonance imaging (fMRI) studies have examined WM development, few have used resting-state fMRI (R-fMRI). Here, we present a systematic R-fMRI examination of age-related differences in the neural indices of verbal WM performance in a cross-sectional pediatric sample (ages: 7-17; n=68), using data-driven approaches. Verbal WM capacity was measured with the digit span task, a commonly used educational and clinical assessment. We found distinct neural indices of digit span forward (DSF) and backward (DSB) performance, reflecting their unique neuropsychological demands. Regardless of age, DSB performance was related to intrinsic properties of brain areas previously implicated in attention and cognitive control, while DSF performance was related to areas less commonly implicated in verbal WM storage (precuneus, lateral visual areas). From a developmental perspective, DSF exhibited more robust age-related differences in brain-behavior relationships than DSB, and implicated a broader range of networks (ventral attention, default, somatomotor, limbic networks) - including a number of regions not commonly associated with verbal WM (angular gyrus, subcallosum). These results highlight the importance of examining the neurodevelopment of verbal WM and of considering regions beyond the "usual suspects".

OBJECTIVE: The study examined implementation outcomes from a large state initiative to support dissemination of multifamily group (MFG) psychoeducation in outpatient mental health settings. METHODS: Thirty-one sites participated in the project. Baseline training in the MFG model was followed by monthly expert consultation delivered in either a group (16 sites) or individual format (15 sites). Research staff assessed fidelity to the MFG model by telephone at baseline and 12, 18, and 24 months and documented time to completion of three key milestones: holding a family joining session, a family educational workshop, and an MFG meeting. RESULTS: Intent-to-train analyses found that 12 sites (39%) achieved high fidelity to the MFG model, and 20 (65%) achieved moderate or high fidelity. Mean scores on the Family Psychoeducation Fidelity Assessment Scale increased over time. Twenty-five sites (81%) conducted at least one joining session, and 20 (65%) conducted at least one MFG. Mean+/-SD time from baseline to the first group was 11.75+/-4.78 months. Programs that held the first joining session within four to 12 months after training were significantly more likely than programs that did not to conduct a group (p<.05). No significant differences were found by consultation format. CONCLUSIONS: Implementation of moderate- to high-fidelity MFG programs in routine outpatient mental health settings is feasible. Sites that moved very quickly or very slowly in early implementation stages were less likely to be successful in conducting an MFG. More research on the efficiency and effectiveness of consultation formats is needed to guide future implementation efforts.

Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring.