Faculty Bibliography

Asian American (ASA) children experience high rates of mental health problems. Although there is a pressing need to utilize population approaches, emerging frameworks from the fields of public and population health have not been applied to ASA children. This paper addresses this gap by first discussing applications of the National Prevention Strategy (NPS), a population strategy developed from the Social Determinants of Health perspective, to guide ASA prevention work. Next, we provide a practical example to illustrate how the NPS can be applied to prevention program design (using ParentCorps as an example) and dissemination and implementation processes to broadly address ASA children's mental health needs. Finally, we present preliminary data on the feasibility of applying this population strategy to ASA families and a framework for researchers who are considering disseminating and implementing evidence-based programs to ASA or ethnic minority pediatric populations.

BACKGROUND: Although DSM-IV attention deficit hyperactivity disorder (ADHD) is known to be associated with numerous adverse outcomes, uncertainties exist about how much these associations are mediated temporally by secondary co-morbid disorders. METHOD: The US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13-17 years (n = 6483 adolescent-parent pairs), assessed DSM-IV disorders with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Statistical decomposition was used to compare direct effects of ADHD with indirect effects of ADHD through temporally secondary mental disorders (anxiety, mood, disruptive behavior, substance disorders) in predicting poor educational performance (suspension, repeating a grade, below-average grades), suicidality (ideation, plans, attempts) and parent perceptions of adolescent functioning (physical and mental health, interference with role functioning and distress due to emotional problems). RESULTS: ADHD had significant gross associations with all outcomes. Direct effects of ADHD explained most (51.9-67.6%) of these associations with repeating a grade in school, perceived physical and mental health (only girls), interference with role functioning and distress, and significant components (34.5-44.6%) of the associations with school suspension and perceived mental health (only boys). Indirect effects of ADHD on educational outcomes were predominantly through disruptive behavior disorders (26.9-52.5%) whereas indirect effects on suicidality were predominantly through mood disorders (42.8-59.1%). Indirect effects on most other outcomes were through both mood (19.8-31.2%) and disruptive behavior (20.1-24.5%) disorders, with anxiety and substance disorders less consistently important. Most associations were comparable for girls and boys. CONCLUSIONS: Interventions aimed at reducing the adverse effects of ADHD might profitably target prevention or treatment of temporally secondary co-morbid disorders.

Journal of Child Psychology and Psychiatry (JCPP) dedicates one whole issue a year to broad-based authoritative reviews by leading authorities on hot topics in the field of child psychology and psychiatry. Widely regarded as a 'go to' resource these Annual Research Reviews (ARRs), constitute the JCPP's flagship issue of that year. The editors have carefully selected the eight reviews in this ARR 2014 issue to be especially timely and significant and then identified key figures who we believed could prepare for our readers definitive 'state of the science' reviews on each topic. In reading the articles once again in order to prepare this Editorial I am struck by the way these diverse articles are united by a recognition of the central importance of developmental perspectives for the science of childhood mental health and disorder. In fact more generally the need for thoroughgoing developmental approaches appears so widely acknowledged that it is regarded by many as a self-evident truth. The articles in this ARR both articulate the importance of this direction of travel wonderfully well and remind us how much farther we have to go to achieve this vision. Their message is that while the conceptual, theoretical, methodological and logistical challenges remain substantial, the limitations of non-developmental approaches, evident in practically every disorder-related sub-domain of our discipline, leave no viable alternative if we are serious about really understanding the factors that shape mental health and disorder across the lifespan. I have extracted four specific lessons that seem especially important in this regard.

In the accompanying Annual Research Review, Horga and colleagues provide a comprehensive overview of the current limitations of magnetic resonance imaging (MRI) of developmental psychopathologies focusing particularly on experimental design. Horga et al. are unsparing in their assessment of the problems that plague current clinical neuroimaging studies. We will not reiterate the long list of deficiencies in the imaging literature, which persist despite its impressive volume (PubMed lists more than 135,000 papers with the terms 'magnetic resonance imaging' and 'brain'). Rather, in this Commentary, while we agree with Horga et al. that neuroimaging approaches merely represent one more types of tool, we look at where this leave us and the prospects (by attending to the lessons thoughtfully laid out by Horga and colleagues on how to place research design at the forefront in clinical neuroimaging) of better times ahead for our understanding of the pathophysiology of child- and adult-onset developmental psychiatric conditions.

The identification of phenotypic associations in high-dimensional brain connectivity data represents the next frontier in the neuroimaging connectomics era. Exploration of brain-phenotype relationships remains limited by statistical approaches that are computationally intensive, depend on a priori hypotheses, or require stringent correction for multiple comparisons. Here, we propose a computationally efficient, data-driven technique for connectome-wide association studies (CWAS) that provides a comprehensive voxel-wise survey of brain-behavior relationships across the connectome; the approach identifies voxels whose whole-brain connectivity patterns vary significantly with a phenotypic variable. Using resting state fMRI data, we demonstrate the utility of our analytic framework by identifying significant connectivity-phenotype relationships for full-scale IQ and assessing their overlap with existent neuroimaging findings, as synthesized by openly available automated meta-analysis (www.neurosynth.org). The results appeared to be robust to the removal of nuisance covariates (i.e., mean connectivity, global signal, and motion) and varying brain resolution (i.e., voxelwise results are highly similar to results using 800 parcellations). We show that CWAS findings can be used to guide subsequent seed-based correlation analyses. Finally, we demonstrate the applicability of the approach by examining CWAS for three additional datasets, each encompassing a distinct phenotypic variable: neurotypical development, Attention-Deficit/Hyperactivity Disorder diagnostic status, and L-DOPA pharmacological manipulation. For each phenotype, our approach to CWAS identified distinct connectome-wide association profiles, not previously attainable in a single study utilizing traditional univariate approaches. As a computationally efficient, extensible, and scalable method, our CWAS framework can accelerate the discovery of brain-behavior relationships in the connectome.

How does visual experience change over development? To investigate changes in visual input over the developmental transition from crawling to walking, thirty 13-month-olds crawled or walked down a straight path wearing a head-mounted eye tracker that recorded gaze direction and head-centered field of view. Thirteen additional infants wore a motion tracker that recorded head orientation. Compared to walkers, crawlers' field of view contained less walls and more floor. Walkers directed gaze straight ahead at caregivers, whereas crawlers looked down at the floor. Crawlers obtained visual information about targets at higher elevations-caregivers and toys-by craning their heads upward and sitting up to bring the room into view. Findings indicate that visual experiences are intimately tied to infants' posture.

Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypoactivity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (>P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.

Purpose Given the metabolic and neurologic side effects of antipsychotics and concerns about the increased risks associated with concomitant use, antipsychotic polypharmacy is a quality concern. This study assessed the operating characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy. Methods A random sample from 10 public mental health clinics and 312 patients met criteria for this study. Medical record extractors were blind to measure status. We examined the prevalence, sensitivity, specificity, and positive predictive value (PPV) in Medicaid claims, testing nine different definitions of antipsychotic polypharmacy, including >14, >60, or >90 days concurrent use of >/=2 antipsychotic agents, each with allowable gaps of up to 0, 14, or 32 days in days' supply of antipsychotic medications. Results All Medicaid claims measure definitions tested had excellent specificity and PPV (>91%). Good to excellent sensitivity was dependent upon use of a 32-day gap allowance, particularly as duration of concurrent antipsychotic use increased. The proposed claims-based measure (90-day concurrent use of >/=2 or more antipsychotics, allowing for a 32-day gap) had excellent specificity (99.1%, 95%CI: 98.2-99.6) and PPV (90.9%, 95%CI: 83.1-95.7) with good sensitivity (79.4%, 95%CI: 70.4-86.6). The overall level of concordance between claims and medical record-based categorization of antipsychotic polypharmacy was high (96.4%, n = 301/312 clients, Cohen's K = 84.7, 95%CI: 75.9-93.5). Discrepant cases were reviewed, and implications are discussed. Conclusions Administrative claims data can be used to construct valid measures of antipsychotic polypharmacy

OBJECTIVE:Clinicians caring for children rely on measures of linear growth as a biomarker of development and overall health. Current reference ranges for height velocity (HV) for US children are unable to provide HV percentiles or Z-scores for early maturing and late maturing children at ages other than age at peak velocity. We present empirically acquired, age-specific reference ranges for HV from a contemporary sample of US youth. STUDY DESIGN/METHODS:Subjects were enrolled in the Bone Mineral Density in Childhood Study, a large, multicenter, multiethnic, contemporary cohort of children (aged 5-19 y at enrollment) from the United States followed for up to 7 years. More than 4000 annual (12 ± 1 mo) HV measurements from approximately 1500 children were available. Pubertal status was determined by breast stage or testicular volume assessed by experienced health providers. Age-specific reference ranges were determined using the LMS method. RESULTS:Reference ranges (third to 97th percentiles) were generated for the entire cohort and for subgroups whose pubertal timing was defined as "earlier," "average," or "later." African American girls experienced earlier pubertal onset and had greater HV at younger ages and lower HV at older ages, compared to non-African American girls; differences did not persist after adjustment for pubertal timing. These differences were not observed for males. CONCLUSIONS:These reference ranges for annual HV can be used to assess growth relative to peers of the same age and sex, with consideration of pubertal timing. Z-scores and exact percentiles for HV can also be determined for population studies.