Faculty Bibliography

We review recent findings related to the neurobiology of infant attachment, emphasizing the role of parenting quality in attachment formation and emotional development. Current findings suggest that the development of brain structures important for emotional expression and regulation (amygdala, prefrontal cortex, hippocampus) is deeply associated with the quality of care received in infancy, with sensitive caregiving providing regulation vital for programming these structures, ultimately shaping the development of emotion into adulthood. Evidence indicates that without sensitive caregiving, infants fail to develop mechanisms needed for later-life emotion and emotion regulation. Research suggests that a sensitive period exists in early life for parental shaping of emotional development, although further cross-species research is needed to discern its age limits, and thus inform interventions.

Hydroxy-4-methoxybenzophenone, also known as benzophenone-3 (BP-3), is a commonly used ultraviolet filter in skincare and as a food additive. Large concentrations of similar phenolic compounds have been detected in urine, amniotic fluid, and placental tissue, thereby raising questions about its impact on reproduction. The objective of this paper was to investigate the reproductive toxicity of BP-3 in humans and animals. In humans, studies showed that high levels of BP-3 exposure could be linked to an increase in male birth weight but a decline in female birth weight and male gestational age. In fish, BP-3 exposure resulted in a decline in egg production, hatching, and testosterone, along with a down-regulation of steroidogenic genes. In rats, a decrease in epididymal sperm density and a prolonged estrous cycle for females was observed. These positive associations may be attributed to an altered estrogen and testosterone balance as a result of endocrine disrupting effects of BP-3. However, the current body of literature is limited by non-uniform exposure and outcome measurements in studies both across and within species and future studies will need to be conducted in a standardized fashion to allow for a more significant contribution to the literature that allows for better comparison across studies.

Microarray studies generate a large number of p-values from many gene expression comparisons. The estimate of the proportion of the p-values sampled from the null hypothesis draws broad interest. The two-component mixture model is often used to estimate this proportion. If the data are generated under the null hypothesis, the p-values follow the uniform distribution. What is the distribution of p-values when data are sampled from the alternative hypothesis? The distribution is derived for the chi-squared test. Then this distribution is used to estimate the proportion of p-values sampled from the null hypothesis in a parametric framework. Simulation studies are conducted to evaluate its performance in comparison with five recent methods. Even in scenarios with clusters of correlated p-values and a multicomponent mixture or a continuous mixture in the alternative, the new method performs robustly. The methods are demonstrated through an analysis of a real microarray dataset.

This study investigates the test-retest reliability of a battery of executive function (EF) tasks with a specific interest in testing whether the method that is used to create a battery-wide score would result in differences in the apparent test-retest reliability of children's performance. A total of 188 4-year-olds completed a battery of computerized EF tasks twice across a period of approximately two weeks. Two different approaches were used to create a score that indexed children's overall performance on the battery-i.e., (1) the mean score of all completed tasks and (2) a factor score estimate which used confirmatory factor analysis (CFA). Pearson and intra-class correlations were used to investigate the test-retest reliability of individual EF tasks, as well as an overall battery score. Consistent with previous studies, the test-retest reliability of individual tasks was modest (rs approximately .60). The test-retest reliability of the overall battery scores differed depending on the scoring approach (rmean = .72; rfactor_score = .99). It is concluded that the children's performance on individual EF tasks exhibit modest levels of test-retest reliability. This underscores the importance of administering multiple tasks and aggregating performance across these tasks in order to improve precision of measurement. However, the specific strategy that is used has a large impact on the apparent test-retest reliability of the overall score. These results replicate our earlier findings and provide additional cautionary evidence against the routine use of factor analytic approaches for representing individual performance across a battery of EF tasks.

Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.

This study examined how to design, staff, and evaluate the feasibility of 2 different models of integrated behavioral health programs in pediatric primary care across primary care sites in the Bronx, NY. Results suggest that the Behavioral Health Integration Program model of pediatric integrated care is feasible and that hiring behavioral health staff with specific training in pediatric, evidence-informed behavioral health treatments may be a critical variable in increasing outcomes such as referral rates, self-reported competency, and satisfaction.

Using a population-based birth cohort in upstate New York (2008-2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots (n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.

BACKGROUND:Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. STUDY DESIGN/METHODS:Observational analysis of 2 clinical trials. SETTING & PARTICIPANTS/METHODS:Participants in the MDRD (Modification of Diet in Renal Disease; n=317) Study and AASK (African American Study of Kidney Disease and Hypertension; n=373). PREDICTORS/METHODS:-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. OUTCOMES/RESULTS:ESRD and all-cause mortality. MEASUREMENTS/METHODS:Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. RESULTS:, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P<0.001), but this association was not significantly different from decline in mGFR (P=0.2). LIMITATIONS/CONCLUSIONS:Small sample size. CONCLUSIONS:, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

BACKGROUND:Depression is associated with poor insulin sensitivity. We evaluated the long-term effects of a cognitive behavioral therapy (CBT) program for prevention of depression on insulin sensitivity in adolescents at risk for type 2 diabetes (T2D) with depressive symptoms. METHODS:One-hundred nineteen adolescent females with overweight/obesity, T2D family history, and mild-to-moderate depressive symptoms were randomized to a 6-week CBT group (n = 61) or 6-week health education (HE) control group (n = 58). At baseline, posttreatment, and 1 year, depressive symptoms were assessed, and whole body insulin sensitivity (WBISI) was estimated from oral glucose tolerance tests. Dual energy X-ray absorptiometry assessed fat mass at baseline and 1 year. Primary outcomes were 1-year changes in depression and insulin sensitivity, adjusting for adiposity and other relevant covariates. Secondary outcomes were fasting and 2-hr insulin and glucose. We also evaluated the moderating effect of baseline depressive symptom severity. RESULTS:Depressive symptoms decreased in both groups (P < .001). Insulin sensitivity was stable in CBT and HE (ΔWBISI: .1 vs. .3) and did not differ between groups (P = .63). However, among girls with greater (moderate) baseline depressive symptoms (N = 78), those in CBT developed lower 2-hr insulin than those in HE (Δ-16 vs. 16 μIU/mL, P < .05). Additional metabolic benefits of CBT were seen for this subgroup in post hoc analyses of posttreatment to 1-year change. CONCLUSIONS:Adolescent females at risk for T2D decreased depressive symptoms and stabilized insulin sensitivity 1 year following brief CBT or HE. Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT.