Faculty Bibliography

Concerns regarding reproducibility of resting-state functional magnetic resonance imaging (R-fMRI) findings have been raised. Little is known about how to operationally define R-fMRI reproducibility and to what extent it is affected by multiple comparison correction strategies and sample size. We comprehensively assessed two aspects of reproducibility, test-retest reliability and replicability, on widely used R-fMRI metrics in both between-subject contrasts of sex differences and within-subject comparisons of eyes-open and eyes-closed (EOEC) conditions. We noted permutation test with Threshold-Free Cluster Enhancement (TFCE), a strict multiple comparison correction strategy, reached the best balance between family-wise error rate (under 5%) and test-retest reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for replicability of amplitude of low-frequency fluctuations (ALFF) for between-subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC differences). Although R-fMRI indices attained moderate reliabilities, they replicated poorly in distinct datasets (replicability < 0.3 for between-subject sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing different sample sizes from a single site, we found reliability, sensitivity and positive predictive value (PPV) rose as sample size increased. Small sample sizes (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also decreased the likelihood that significant results reflect "true" effects (PPV < 0.26) in sex differences. Our findings have implications for how to select multiple comparison correction strategies and highlight the importance of sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum Brain Mapp 00:000-000, 2017. (c) 2017 Wiley Periodicals, Inc.

Childhood mental health disorders are on the rise in the United States. To ensure equitable access to care, it is important to examine the characteristics of children and families who access services. This study compares the demographic characteristics of two samples of families who participated in National Institute of Mental Health-funded studies of a Multiple Family Group model, entitled the 4Rs and 2Ss Multiple Family Group (4Rs and 2Ss) in New York City. One sample is currently receiving services, and the other received services a decade ago. Significant differences in demographic characteristics were found between the two samples pertaining to child race, child nativity, caregiver age, primary caregiver, caregiver marital status, caregiver race, caregiver education, caregiver employment, and family income. Families currently engaging in the public mental health service system are primarily White, and are less disadvantaged than families a decade ago. These differences are examined in light of changing policy and epidemiological trends, and potential unintended consequences are discussed.

A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a "difference in differences" methodology)]. The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.

Emotional dysregulation (ED) is a dysfunction in modifying an emotional state in an adaptive and goal oriented way, with excitability, ease anger, and mood lability. It is present in up to 70% of adults with ADHD, regardless of other comorbidities, and substantially worsens the psychosocial outcomes of the disorder. Besides fronto-parietal circuits mediating top-down control, brain regions involved in bottom-up processes (e.g., amygdala, orbitofrontal cortex, and ventral striatum) are implicated in ED. We performed a systematic review/meta-analysis of double-blind randomized controlled trials of ADHD medications to assess their effects on ED in adults with ADHD. We searched an extensive set of databases, international trials registries, and contacted study authors/drug companies for unpublished data. We retained 21 trials. We found small-to-moderate effects (methylphenidate: SMD=0.34, 95% CI=0.23-0.45; atomoxetine: SMD=0.24, 95% CI=0.15-0.34; lisdexamfetamine: SMD=0.50, 95% CI=0.21-0.8). We suggest that, whilst ADHD medications are effective on ADHD core symptoms, they may be less effective on bottom-up mechanisms underlying ED. Further research on novel pharmacological and non-pharmacological strategies for ED in adults with ADHD is warranted.

OBJECTIVE/UNASSIGNED:are considered as potential moderators. DESIGN/UNASSIGNED:age = 4.43 years). Parent and teacher assessments of child internalizing and externalizing were also collected at baseline and 12 months later. RESULTS/UNASSIGNED:At Time 1, male child gender was positively correlated with concurrent spanking; familial social support and U.S. American cultural knowledge were negatively correlated with mothers' spanking. Verbal punishment at Time 1 was associated with externalizing problems at Time 2 among both Mexican and Dominican American children, and this relation was not moderated. Additionally, verbal punishment was associated with Time 2 child internalizing problems among Mexican American children. There were no significant associations between spanking and later child internalizing or externalizing behaviors. CONCLUSION/UNASSIGNED:It is important that researchers examine both physical and verbal discipline strategies to understand their unique influences on Latino child outcomes, as well as contextual influences that may elucidate the use and long-term effects of spanking and verbal punishment on Latino children at different developmental stages.

Background: Chronic illness in children has adverse effects on family members besides the patient and can impact the integrity and function of the family unit. Most previous studies have examined a single disease entity. However, there has been limited assessment comparing the effect of different illnesses on family function.
Method(s): Established patients treated in the pediatric ambulatory Nephrology or DM clinics were included in the study. Their parents were asked to complete the 2-page Pediatric Quality-of-Life Family Impact Module (PedsQL-FIM), version 2.0, a validated survey instrument. Clinical and laboratory data were retrieved from the electronic health record. Data were summarized as mean+/-SD. Disease group and child age were entered as predictors in linear regression analyses with FIM total and subscale scores as outcome variables. Comparisons between groups were assessed using paired t-tests.
Result(s): 96 patients (43 F: 53 M) were evaluated in the Nephrology Clinic and 55 (30 F: 25 M) in the DM Clinic. The mean age of the patients was 13.0+/-3.9 and 10.4+/- 6.3 yr, respectively. Within the KD sample, older age was significantly associated with lower scores on all FIM subscale scores. Gender was not a significant predicator for FIM scores in either disease group. Controlling for age, chronic illness group was a significant predictor of the FIM total and subscale scores. Parents of D patients endorsed significantly lower total FIM scores compared to the KD patients (D 58+/-16; KD 79+/-17 p <0.001) as well as on subscales of physical, emotional, social, and cognitive functioning, communication, worry, daily activities, family relationships, and reports of health-related quality of life (P<0.01).
Conclusion(s): Our findings confirm that chronic illness in childhood adversely affects a wide range of aspects of family function. The impact is greater in older children with KD and varies depending on the disease context. Families with children who have DM manifested greater disturbances than those with children who have isolated KD. Further study is warranted to assess the effects of the underlying renal disease and intensity of medical care and whether there are specific features can be used to identify vulnerable families

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.