Faculty Bibliography

OBJECTIVE: Although schools are identified as critical for detecting youth mental disorders, little is known about whether the number of mental health providers and types of resources that they offer influence student mental health service use. Such information could inform the development and allocation of appropriate school-based resources to increase service use. This article examines associations of school resources with past-year mental health service use among students with 12-month DSM-IV mental disorders. METHOD: Data come from the U.S. National Comorbidity Survey Adolescent Supplement (NCS-A), a national survey of adolescent mental health that included 4,445 adolescent-parent pairs in 227 schools in which principals and mental health coordinators completed surveys about school resources and policies for addressing student emotional problems. Adolescents and parents completed the Composite International Diagnostic Interview and reported mental health service use across multiple sectors. Multilevel multivariate regression was used to examine associations of school mental health resources and individual-level service use. RESULTS: Nearly half (45.3%) of adolescents with a 12-month DSM-IV disorder received past-year mental health services. Substantial variation existed in school resources. Increased school engagement in early identification was significantly associated with mental health service use for adolescents with mild/moderate mental and behavior disorders. The ratio of students to mental health providers was not associated with overall service use, but was associated with sector of service use. CONCLUSIONS: School mental health resources, particularly those related to early identification, may facilitate mental health service use and may influence sector of service use for youths with DSM disorders.

Objective Exercise has widely documented cardioprotective effects, but the mechanisms underlying these effects are not entirely known. Previously, we demonstrated that aerobic but not strength training lowered resting heart rate and increased cardiac vagal regulation, changes that were reversed by sedentary deconditioning. Here, we focus on the sympathetic nervous system and test whether aerobic training lowers levels of cardiovascular sympathetic activity in rest and that deconditioning would reverse this effect. Methods We conducted a randomized controlled trial contrasting the effects of aerobic (A) versus strength (S) training on indices of cardiac (preejection period, or PEP) and vascular (low-frequency blood pressure variability, or LF BPV) sympathetic regulation in 149 young, healthy, and sedentary adults. Participants were studied before and after conditioning, as well as after 4 weeks of sedentary deconditioning. Results As previously reported, aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. Contrary to prediction, there was no differential effect of training on either PEP (A: mean [SD] -0.83 [7.8] milliseconds versus S: 1.47 [6.69] milliseconds) or LF BPV (A: mean [SD] -0.09 [0.93] ln mm Hg(2) versus S: 0.06 [0.79] ln mm Hg (2)) (both p values > .05). Conclusions These findings, from a large randomized controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on resting state cardiovascular indices of PEP and LF BPV. These results indicate that in healthy, young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in resting sympathetic activity. Trial Registration Clinicaltrials.gov identifier: NCT00358137.

PURPOSE: To examine prevalence and correlates of five mental health (MH) problems among 12-17.5 year olds investigated by child welfare. METHODS: Data from the National Survey on Child and Adolescent Well-being (NSCAW II) were analyzed to examine depression, anxiety, substance use/abuse, suicidality, and attention deficit hyperactivity disorder (ADHD) as reported by teens and their caregivers. In a sample of 815 adolescents, prevalence for each MH problem and correlates (e.g., age, placement location) were identified using bivariate and multivariable logistic analyses. RESULTS: After investigation for maltreatment, 42.7% of teens reported at least one MH problem, regardless of placement. Nine percent reported depression, 13.9% reported suicidality, 23% had substance use/abuse, 13.5% reported anxiety, and 18.6% had ADHD. Of 332 teens with any MH problem, 52.1% reported only one problem, 28.3% had two problems, and 19.6% had >/= three problems. Teens with prior out-of-home placement had odds 2.29 times higher of reporting a MH problem and odds 2.12 times higher of reporting substance use/abuse. Males were significantly less likely to report depression. Older teens were more likely to report substance use/abuse. Black teens were significantly less likely to report suicidality and ADHD and almost half as likely to report anxiety. Teens with a chronic health condition and teens whose caregiver reported depression had more than twice the odds of reporting anxiety. CONCLUSIONS: This study highlights high rates of MH problems in teens of all ages and placement locations and suggests that all teens involved with child welfare should be screened for MH problems, regardless of initial placement status.

OBJECTIVES: Controversy surrounds the diagnostic categorization of children with episodic moods that cause impairment, but do not meet DSM-IV criteria for bipolar I (BD-I) or bipolar II (BD-II) disorder. This study aimed to characterize the degree to which these children, who meet criteria for bipolar disorder not otherwise specified (BD-NOS), are similar to those with full syndromal BD, versus those with no bipolar spectrum diagnosis (no BSD). METHODS: Children aged 6-12 years were recruited from nine outpatient clinics, preferentially selected for higher scores on a 10-item screen for manic symptoms. Interviews with the children and their primary caregivers assessed a wide array of clinical variables, as well as family history. RESULTS: A total of 707 children [mean +/- standard deviation (SD) 9.4 +/- 1.9 years old] were evaluated at baseline, and were diagnosed with BD-I (n = 71), BD-II (n = 3), BD-NOS (including cyclothymia; n = 88), or no BSD (n = 545). Compared to BD-I, the BD-NOS group had less severe past functional impairment. However, current symptom severity and functional impairment did not differ between BD-NOS and BD-I, even though both groups were significantly more symptomatic and impaired than the no BSD group. Parental psychiatric history was similar for the BD-NOS and BD-I groups, and both were more likely than the no BSD group to have a parent with a history of mania. Rates of elated mood did not differ between BD-NOS and BD-I youth. CONCLUSIONS: Children with BD-NOS and BD-I are quite similar, but different from the no BSD group, on many phenomenological measures. These findings support the hypothesis that BD-NOS is on the same spectrum as BD-I.

OBJECTIVE:To evaluate the impact of an early childhood, family-centered, school-based intervention on children's kindergarten academic achievement.METHODS:This was a cluster (school) randomized controlled trial with assessments from pre-kindergarten (pre-k) entry through the end of kindergarten. The setting was 10 public elementary schools with 26 pre-k classes in 2 school districts in urban disadvantaged neighborhoods serving a largely black, low-income population. Participants were 1050 black and Latino, low-income children (age 4; 88% of pre-k population) enrolled in 10 schools over 4 years. Universal intervention aimed to promote self-regulation and early learning by strengthening positive behavior support and effective behavior management at home and school, and increasing parent involvement in education. Intervention included after-school group sessions for families of pre-k students (13 2-hour sessions; co-led by pre-k teachers) and professional development for pre-k and kindergarten teachers. The outcome measures were standardized test scores of kindergarten reading, writing, and math achievement by independent evaluators masked to intervention condition (primary outcome); developmental trajectories of teacher-rated academic performance from pre-k through kindergarten (secondary outcome).RESULTS:Relative to children in control schools, children in intervention schools had higher kindergarten achievement test scores (Cohen's d = 0.18, mean difference = 2.64, SE = 0.90, P = .03) and higher teacher-rated academic performance (Cohen's d = 0.25, mean difference = 5.65, SE = 2.34, P = .01).CONCLUSIONS:Early childhood population-level intervention that enhances both home and school environments shows promise to advance academic achievement among minority children from disadvantaged, urban neighborhoods.

Fetal Alcohol Spectrum Disorder (FASD) is a general diagnosis for those exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of fetal alcohol exposure. It is among the most common causes of mental deficits today. Those impacted are left to rely on advances in our understanding of the nature of early alcohol-induced disorders toward human therapies. Research findings over the last decade have developed a model where ethanol-induced neurodegeneration impacts early neural circuit development, thereby perpetuating subsequent integration and plasticity in vulnerable brain regions. Here we review our current knowledge of FASD neuropathology based on discoveries of long-lasting neurophysiological effects of acute developmental ethanol exposure in animal models. We discuss the important balance between synaptic excitation and inhibition in normal neural network function, and relate the significance of that balance to human FASD as well as related disease states. Finally, we postulate that excitation/inhibition imbalance caused by early ethanol-induced neurodegeneration results in perturbed local and regional network signaling and therefore neurobehavioral pathology.

BACKGROUND: Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental disorders that affect 1 in 88 children in the US. Previous exome sequencing studies on family trios have implicated a role for rare, de-novo mutations in the pathogenesis of autism. METHODS: To examine the utility of whole-genome sequencing to identify inherited disease candidate variants and genes, we sequenced two probands from a large pedigree, including two parents and eight children. We evaluated multiple analytical strategies to identify a prioritized list of candidate genes. RESULTS: By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies. CONCLUSIONS: Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases.

The BOLD signal measured in fMRI studies depends not only on neuronal activity, but also on other parameters like tissue vascularization, which may vary between subjects and between brain regions. A correction for variance from vascularization effects can thus lead to improved group statistics by reducing inter-subject variability. The fractional amplitude of low-frequency fluctuations (fALFF) as determined in a resting-state scan has been shown to be dependent on vascularization. Here we present a correction method termed RESCALE (REsting-state based SCALing of parameter Estimates) that uses local information to compute a voxel-wise scaling factor based on the correlation structure of fALFF and task activation parameter estimates from within a cube of 3 x 3 x 3 surrounding that voxel. The scaling method was used on a visuo-motor paradigm and resulted in a consistent increase in t-values in all task-activated cortical regions, with increases in peak t-values of 37.0% in the visual cortex and 12.7% in the left motor cortex. The RESCALE method as proposed herein can be easily applied to all task-based fMRI group studies provided that resting-state data for the same subject group is also acquired.

Analyses of intrinsic fMRI BOLD signal fluctuations reliably reveal correlated and anticorrelated functional networks in the brain. Because the BOLD signal is an indirect measure of neuronal activity and anticorrelations can be introduced by preprocessing steps, such as global signal regression, the neurophysiological significance of correlated and anticorrelated BOLD fluctuations is a source of debate. Here, we address this question by examining the correspondence between the spatial organization of correlated BOLD fluctuations and correlated fluctuations in electrophysiological high gamma power signals recorded directly from the cortical surface of 5 patients. We demonstrate that both positive and negative BOLD correlations have neurophysiological correlates reflected in fluctuations of spontaneous neuronal activity. Although applying global signal regression to BOLD signals results in some BOLD anticorrelations that are not apparent in the ECoG data, it enhances the neuronal-hemodynamic correspondence overall. Together, these findings provide support for the neurophysiological fidelity of BOLD correlations and anticorrelations.