Faculty Bibliography

Noradrenergic signaling in the amygdala is important for processing threats and other emotionally salient stimuli, and β-adrenergic receptor activation is known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile animals. Nevertheless, intracellular recordings have not yet been conducted to determine the effect of β-adrenergic receptor activation on spike properties in the adult LA, despite the potential significance of developmental changes between adolescence and adulthood. Here we demonstrate that the β-adrenergic agonist isoproterenol (15 μM) enhances spike frequency in dorsal LA principal neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex-matched adults. Furthermore, we find that the age-dependent effect of isoproterenol on spike frequency is occluded by the GABA_A receptor blocker picrotoxin (75 μM), suggesting that β-adrenergic receptors downregulate tonic inhibition specifically in juvenile animals. These findings indicate a significant shift during adolescence in the cellular mechanisms of β-adrenergic modulation in the amygdala. NEW & NOTEWORTHY β-Adrenergic receptors (β-ARs) in amygdala are important in processing emotionally salient stimuli. Most cellular recordings have examined juvenile animals, while behavioral data are often obtained from adults. We replicate findings showing that β-ARs enhance spiking of principal cells in the lateral amygdala of juveniles, but we fail to find this in adults. These findings have notable scientific and clinical implications regarding the noradrenergic modulation of threat processing, alterations of which underlie fear and anxiety disorders.

OBJECTIVE:This study compared health care access and utilization among adults with serious psychological distress by race-ethnicity and gender in years surrounding implementation of the Affordable Care Act. METHODS:Data for adults ages 18 to 64 with serious psychological distress in the 2006-2015 National Health Interview Survey (N=8,940) were analyzed by race-ethnicity and gender on access and utilization indicators: health insurance coverage, insufficient money to buy medications, delay in health care, insufficient money for health care, visited a doctor more than ten times in the past 12 months, change in place of health care, change in place of health care because of insurance, saw a mental health provider in the past 12 months, and insufficient money for mental health care. RESULTS:The proportions of white and black adults with serious psychological distress were largest in the South, the region with the largest proportion of persons with serious psychological distress and no health coverage. Multivariate models that adjusted for health coverage, sociodemographic characteristics, health conditions, region, and year indicated that whites were more likely than blacks to report insufficient money for medications and mental health care and delays in care. A greater proportion of whites used private coverage, compared with blacks and Hispanics, and blacks were more likely than all other racial-ethnic groups to have Medicaid. CONCLUSIONS:More research is needed on health care utilization among adults with serious psychological distress. In this group, whites and those with private coverage reported poor utilization, compared with other racial-ethnic groups and those with Medicaid, respectively.

OBJECTIVE:Impulsive choices can lead to suboptimal decision making, a tendency which is especially marked in individuals with ADHD. We compared two different paradigms assessing impulsive choice: the simple choice paradigm (SCP) and the temporal discounting paradigm (TDP). METHOD/METHODS:Random effects meta-analyses on 37 group comparisons (22 SCP; 15 TDP) consisting of 3.763 participants (53% ADHD). RESULTS:Small-to-medium effect sizes emerged for both paradigms, confirming that participants with ADHD choose small immediate over large delayed rewards more frequently than controls. Moderation analyses show that offering real rewards in the SCP almost doubled the odds ratio for participants with ADHD. CONCLUSION/CONCLUSIONS:We suggest that a stronger than normal aversion toward delay interacts with a demotivating effect of hypothetical rewards, both factors promoting impulsive choice in participants with ADHD. Furthermore, we suggest the SCP as the paradigm of choice due to its larger ecological validity, contextual sensitivity, and reliability.

Socioeconomic disadvantage (SED) experienced in early life is linked to a range of risk behaviors and diseases. Neuroimaging research indicates that this association is mediated by functional changes in corticostriatal reward systems that modulate goal-directed behavior, reward evaluation, and affective processing. Existing research has focused largely on adults and within-household measures as an index of SED, despite evidence that broader community-level SED (e.g., neighborhood poverty levels) has significant and sometimes distinct effects on development and health outcomes. Here, we test effects of both household- and community-level SED on resting-state functional connectivity (rsFC) of the ventral striatum (VS) in 100 racially and economically diverse children and adolescents (ages 6-17). We observed unique effects of household income and community SED on VS circuitry such that higher community SED was associated with reduced rsFC between the VS and an anterior region of the medial prefrontal cortex (mPFC), whereas lower household income was associated with increased rsFC between the VS and the cerebellum, inferior temporal lobe, and lateral prefrontal cortex. Lower VS-mPFC rsFC was also associated with higher self-reported anxiety symptomology, and rsFC mediated the link between community SED and anxiety. These results indicate unique effects of community-level SED on corticostriatal reward circuitry that can be detected in early life, which carries implications for future interventions and targeted therapies. In addition, our findings raise intriguing questions about the distinct pathways through which specific sources of SED can affect brain and emotional development.

BACKGROUND:Multiple chronic health conditions have been associated with exposure to the September 11, 2001 World Trade Center (WTC) terrorist attacks (9/11). We assessed whether excess deaths occurred during 2003-2014 among persons directly exposed to 9/11, and examined associations of 9/11-related exposures with mortality risk. MATERIALS AND METHODS/METHODS:Deaths occurring in 2003-2014 among members of the World Trade Center Health Registry, a cohort of rescue/recovery workers and lower Manhattan community members who were exposed to 9/11, were identified via linkage to the National Death Index. Participants' overall levels of 9/11-related exposure were categorized as high, intermediate, or low. We calculated standardized mortality ratios (SMR) using New York City reference rates from 2003 to 2012. Proportional hazards were used to assess associations of 9/11-related exposures with mortality, accounting for age, sex, race/ethnicity and other potential confounders. RESULTS:We identified 877 deaths among 29,280 rescue/recovery workers (3.0%) and 1694 deaths among 39,643 community members (4.3%) during 308,340 and 416,448 person-years of observation, respectively. The SMR for all causes of death was 0.69 [95% confidence interval (CI) 0.65-0.74] for rescue/recovery workers and 0.86 (95% CI 0.82-0.90) for community members. SMRs for diseases of the cardiovascular and respiratory systems were significantly lower than expected in both groups. SMRs for several other causes of death were significantly elevated, including suicide among rescue recovery workers (SMR 1.82, 95% CI 1.35-2.39), and brain malignancies (SMR 2.25, 95% CI 1.48-3.28) and non-Hodgkin's lymphoma (SMR 1.79, 95% CI 1.24-2.50) among community members. Compared to low exposure, both intermediate [adjusted hazard ratio (AHR) 1.36, 95% CI 1.10-1.67] and high (AHR 1.41, 95% CI 1.06-1.88) levels of 9/11-related exposure were significantly associated with all-cause mortality among rescue/recovery workers (p-value for trend 0.01). For community members, intermediate (AHR 1.13, 95% CI 1.01-1.27), but not high (AHR 1.14, 95% CI 0.94-1.39) exposure was significantly associated with all-cause mortality (p-value for trend 0.03). AHRs for associations of overall 9/11-related exposure with heart disease- and cancer-related mortality were similar in magnitude to those for all-cause mortality, but with 95% CIs crossing the null value. CONCLUSIONS:Overall mortality was not elevated. Among specific causes of death that were significantly elevated, suicide among rescue/recovery workers is a plausible long-term consequence of 9/11 exposure, and is potentially preventable. Elevated mortality due to other causes, including non-Hodgkin's lymphoma and brain cancer, and small but statistically significant associations of 9/11-related exposures with all-cause mortality hazard warrant additional surveillance.

This study tests whether a parenting intervention for families of preschoolers at risk for conduct problems can prevent later risk for intimate partner violence (IPV). Ninety-nine preschoolers at familial risk for conduct problems were randomly assigned to intervention or control conditions. Ten years later, 45 preschoolers and 43 of their siblings completed an assessment of their romantic relationships, including measures of physical and psychological IPV. The study focuses on the 54 females, including targets (n = 27) and siblings (n = 27) who participated in a 10-year follow-up (M age = 16.5, SD = 5.2, range = 10-28). Using an intent-to-treat (ITT) design, multivariate regressions suggest that females from families randomly assigned to intervention in early childhood scored lower than those in the control condition on perceptions of dating violence as normative, beliefs about IPV prevalence, exposure to IPV in their own peer group, and expected sanction behaviors for IPV perpetration and victimization. Findings suggest that early parenting intervention may reduce association of high-risk females with aggressive peers and partners in adolescence.

BACKGROUND:Accurate assessment of pediatric bipolar disorder (BD) is important for allocating appropriate treatment, but it is complicated by significant heterogeneity in symptom presentation and high rates of comorbidity. Investigating clinical subtypes of the disorder may help to clarify diagnostic boundaries and inform targeted treatment. This study used a full diagnostic instrument to examine symptom patterns among youth with BD. METHOD:Trained interviewers completed the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with 71 children (7 to 13 y of age) and families as part of the baseline assessment for a randomized clinical trial of Child- and Family-focused Cognitive-Behavioral Therapy (CFF-CBT) compared with treatment as usual (TAU) for pediatric BD. All participants met DSM-IV-TR criteria for a bipolar spectrum disorder. Hierarchical and K-means cluster analyses were performed. Resultant clusters were compared on symptom severity and psychosocial functioning at baseline and across treatment. RESULTS:Two distinct symptom profiles emerged: "dysregulated/defiant" and "classic presentation." The dysregulated/defiant cluster was characterized by more externalizing and disruptive behaviors, whereas the classic cluster presented with more severe depression, hallmark manic symptoms, anxiety, and inattention. CFF-CBT consistently promoted psychosocial coping skills, such as problem solving and self-control, for the dysregulated/defiant cluster. TAU also promoted these skills among the individuals in the classic presentation group but not those with symptoms in the dysregulated/defiant cluster. DISCUSSION:Pediatric BD may be characterized by distinct phenotypes with unique etiologies and pathways to impairment. The use of a parametric approach to classify the diverse symptom presentations helped yield valuable insights into how to promote the best prognosis for improved functional outcomes in CFF-CBT versus TAU for youth with pediatric BD.

BACKGROUND:Sleep disturbances, in particular insomnia, represent a common problem in children with neurodevelopmental disabilities (NDDs). Currently, there are no approved medications for insomnia in children by the US Food and Drug Administration or European Medicines Agency and therefore they are prescribed off-label. We critically reviewed pediatric literature on drugs as well as nonpharmacological (behavioral) interventions used for sleep disturbances in children with NDDs. METHODS:, and Embase), and Web of Knowledge databases were searched through February 12, 2017, with no language restrictions. Two authors independently and blindly performed the screening. RESULTS:Good sleep practices and behavioral interventions, supported by moderate-to-low level evidence, are the first recommended treatments for pediatric insomnia but they are often challenging to implement. Antihistamine agents, such as hydroxyzine or diphenhydramine, are the most widely prescribed sedatives in the pediatric practice but evidence supporting their use is still limited. An increasing body of evidence supports melatonin as the safest choice for children with NDDs. Benzodiazepines are not recommended in children and should only be used for transient insomnia, especially if daytime anxiety is present. Only few studies have been carried out in children's and adolescents' zolpidem, zaleplon, and eszopiclone, with contrasting results. Limited evidence supports the use of alpha-agonists such as clonidine to improve sleep onset latency, especially in attention deficit/hyperactivity disorder subjects. Tricyclic antidepressants, used in adults with insomnia, are not recommended in children because of their safety profile. Trazodone and mirtazapine hold promise but require further studies. CONCLUSIONS:Here, we provided a tentative guide for the use of drugs for insomnia in children with NDDs. Well-controlled studies employing both objective polysomnography and subjective sleep measures are needed to determine the efficacy, effectiveness, and safety of the currently prescribed pediatric sleep medicines in children with NDDs.