Faculty Bibliography

OBJECTIVES: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. METHODS: Participants were children with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch) subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. RESULTS: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. CONCLUSIONS: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).

Contrary to the "model minority" myth, Asian American children, especially those from low-income immigrant families, are at risk for both behavioral and emotional problems early in life. Little is known, however, about the underlying developmental mechanisms placing Asian American children at risk, including the role of cultural adaptation and parenting. This study examined cultural adaptation, parenting practices and culture related parenting values and child mental health in a sample of 157 English speaking Asian American immigrant families of children enrolled in early childhood education programs in low-income, urban neighborhoods. Overall, cultural adaptation and parenting cultural values and behaviors were related to aspects of child mental health in meaningful ways. Parents' cultural value of independence appears to be especially salient (e.g., negatively related to behavior problems and positively related to adaptive behavior) and significantly mediates the link between cultural adaptation and adaptive behavior. Study findings have implications for supporting Asian American immigrant families to promote their young children's mental health.

OBJECTIVE:Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure. METHOD/METHODS:As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status-matched controls (14-18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume. RESULTS:CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset. CONCLUSION/CONCLUSIONS:We found both similarities and differences between males and females in CD-cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments.

AIM: This proof-of-concept study examined if early trauma influences features of schizophrenia, consistent with hypothalamic-pituitary-adrenal (HPA) axis activation. METHODS: Early trauma and current perceived stress were assessed in 28 treated schizophrenia cases, along with salivary cortisol, brain volumes, cognition and symptoms. RESULTS: Early trauma predicted more positive (r = .66, P = .005) and dysthymia symptoms (r -.65, P = .007), but less negative symptoms (r = -.56, P = .023), as well as reduced whole brain volumes (r = .50, P = .040) and increased amygdala to whole brain volume ratios (r = .56, P = .018). Larger volume reductions accompanied cortisol levels: evening values predicted smaller whole brain and hippocampal volumes whereas afternoon levels only significantly predicted smaller brain volumes in women. Sex differences were demonstrated between early trauma and cognition, with better cognition in traumatized women than other women and no male effects. Current perceived stress was related to dysthymia (especially in women) and diminished sense of purpose and social drive (especially in men). CONCLUSIONS: These results suggest that early trauma and current stress impact features of schizophrenia, consistent with stress sensitization and increased dopamine activity for treatment refractory positive symptoms, as well as the cascade of increased morning cortisol, reduced brain volumes, and depressive and deficit symptoms. Conversely, cognitive deficits and negative symptoms may arise from a distinct diathesis. The sex differences accord with the literature on human HPA function and stress responses. Early trauma may be a stressor in the aetiopathophysiology of schizophrenia, particularly for cases with treatment refractory positive symptoms, and may guide future treatment development.

Objective/UNASSIGNED:To identify factors associated with early initiation and achievement of therapeutic hypothermia (TH) in newborns with hypoxic-ischemic encephalopathy (HIE). Methods/UNASSIGNED:Retrospective cohort study of newborns who received TH according to National Institute of Child Health and Human Development (NICHD) criteria in two academic level 3 Neonatal Intensive Care Units (NICU) between 2009 and 2013. All infants were transported by a neonatal transport team (NNTT). Multivariate linear regression including who initiated cooling and degree of resuscitation in the model was performed. Results/UNASSIGNED:Two hundred and seven infants were included. Waiting for advice from a tertiary care NICU was independently associated with a 50 minute delay in the median time of initiation of TH. The need for extensive resuscitation (cardiopulmonary resuscitation [CPR] or epinephrine) was independently associated with a reduction of 43 minutes in the median time to reach target core temperature. Log-transformed time to initiation of TH was associated with time to reach target core temperature (P<0.001). A doubling of time to initiation of TH corresponds to a 24% (95% CI 18% to 30%) increase in median time to reach target core temperature. Conclusions/UNASSIGNED:Initiating passive cooling at the referring centre, before transfer, is critical to faster achievement of target core temperature in asphyxiated infants. Greater outreach education and development of clinical care pathways are needed to improve optimal delivery of TH to enhance outcome.

OBJECTIVE: Efforts to promote early brain and child development (EBCD) include initiatives to support healthy parent-child relationships, tools to identify family social-emotional risk factors, and referrals to community programs to address family risk factors. We sought to examine if pediatricians perceive barriers to implementing these activities, and if they utilize resources to address those barriers. METHOD: Data were analyzed from 304 non-trainee pediatricians who practice general pediatrics and completed a 2013 American Academy of Pediatrics Periodic Survey. Sample weights were used to decrease non-response bias. Bivariate comparisons and multivariable regression analyses were conducted. RESULTS: At least half of the pediatricians agreed that barriers to promoting EBCD include: a lack of tools to promote healthy parent-child relationships, a lack of tools to assess the family environment for social-emotional risk factors, and a lack of local resources to address family risks. Endorsing a lack of tools to assess the family environment as a barrier was associated with using fewer screening tools and community resources. Endorsing a lack of local resources as a barrier was associated with using fewer community resources and fewer initiatives to promote parent-child relationships. Interest in pediatric mental health was associated with using more initiatives to promote healthy parent-child relationships, screening tools, and community resources. CONCLUSION: Although the majority of pediatricians perceive barriers to promoting EBCD, few are routinely using available resources to address these barriers. Addressing pediatricians' perceived barriers and encouraging interest in pediatric mental health may increase resource utilization and enhance efforts to promote EBCD.

PURPOSE/BACKGROUND: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist d-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia. METHODS/PROCEDURES: Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance. FINDINGS/RESULTS: No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments. IMPLICATIONS/CONCLUSIONS: These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.

Studies have reported associations between cortical thickness (CT) and socioeconomic status (SES), as well as between CT and cognitive outcomes. However, findings have been mixed as to whether CT explains links between SES and cognitive performance. In the current study, we hypothesized that this inconsistency may have arisen from the fact that socioeconomic factors (family income and parental education) may moderate the relation between CT and neurocognitive skills. Results indicated that associations between CT and cognitive performance did vary by SES for both language and executive function (EF) abilities. Across all ages, there was a negative correlation between CT and cognitive skills, with thinner cortices associated with higher language and EF scores. Similarly, across all cognitive skills, children from higher-SES homes outperformed their age-matched peers from lower-SES homes. Moderation analyses indicated that the impact of SES was not constant across CT, with SES more strongly predictive of EF skills among children with thicker cortices and more strongly predictive of language skills among children with thinner cortices. This suggests that socioeconomic advantage may in some cases buffer against a neurobiological risk factor for poor performance. These findings suggest that links between brain structure and cognitive processes vary by family socioeconomic circumstance.

Restless legs syndrome (RLS) is a relatively common neurological disorder in childhood, although it is usually overlooked due to the atypical presentation in children and associated comorbid conditions that may affect its clinical presentation. Here, we aimed to perform, for the first time, a systematic review of studies reporting the association between RLS in children and adolescents (<18 y) and somatic or neuropsychiatric conditions. We searched for peer-reviewed studies in PubMed, Ovid (including PsycINFO, Ovid MEDLINE(R), and Embase), Web of Knowledge (Web of Science, Biological abstracts, BIOSIS, FSTA) through November 2015, with no language restrictions. We found 42 pertinent studies. Based on the retrieved studies, we discuss the association between RLS and a number of conditions, including growing pains, kidney disease, migraine, diabetes, epilepsy, rheumatologic disorders, cardiovascular disease, liver and gastrointestinal disorders, and neuropsychiatric disorders (e.g., attention deficit hyperactivity disorder (ADHD), depression, and conduct disorder). Our systematic review provides empirical evidence supporting the notion that RLS in children is comorbid with a number of somatic and neuropsychiatric conditions. We posit that the awareness on comorbid diseases/disorders is pivotal to improve the diagnosis and management of RLS and might suggest fruitful avenues to elucidate the pathophysiology of RLS in children.