Faculty Bibliography

OBJECTIVE: This study has been specifically designed to investigate very low frequency neuronal oscillations (VLFO, <0.5 Hz) during resting states and during goal-directed tasks of graded difficulty levels, quantify the changes that the slow waves undergo in these conditions and compare them with those for higher frequency bands (namely delta, theta and alpha). METHODS: To this end we developed a multistage signal processing methodology comprising blind source separation coupled with a neural network based feature extraction and classification method. RESULTS: Changes in the amplitude and phase of brain sources estimates in the VLF band between rest and task were enhanced with increased task difficulty, but remained lower than those experienced in higher frequency bands. The slow wave variations were also significantly correlated with task performance measures, and hence with the level of task-directed attention. CONCLUSIONS: These findings suggest that besides their prominent sensitivity to external stimulation, VLFOs also contribute to the cortical ongoing background activity which may not be specifically related to task-specific attention and performance. SIGNIFICANCE: Our work provides important insight into the association between VLF brain activity and conventional EEG frequency bands, and presents a novel framework for assessing neural activity during various mental conditions and psychiatric states.

OBJECTIVE: No empirical studies on the DSM-5 proposed disruptive mood dysregulation disorder have yet been published. This study estimated prevalence, comorbidity, and correlates of this proposed disorder in the community. METHOD: Prevalence rates were estimated using data from three community studies involving 7,881 observations of 3,258 participants from 2 to 17 years old. Disruptive mood dysregulation disorder was diagnosed using structured psychiatric interviews. RESULTS: Three-month prevalence rates for meeting criteria for disruptive mood dysregulation disorder ranged from 0.8% to 3.3%, with the highest rate in preschoolers. Rates dropped slightly with the strict application of the exclusion criterion, but they were largely unaffected by the application of onset and duration criteria. Disruptive mood dysregulation co-occurred with all common psychiatric disorders. The highest levels of co-occurrence were with depressive disorders (odds ratios between 9.9 and 23.5) and oppositional defiant disorder (odds ratios between 52.9 and 103.0). Disruptive mood dysregulation occurred with another disorder 62%-92% of the time, and it occurred with both an emotional and a behavioral disorder 32%-68% of the time. Affected children displayed elevated rates of social impairments, school suspension, service use, and poverty. CONCLUSIONS: Disruptive mood dysregulation disorder is relatively uncommon after early childhood, frequently co-occurs with other psychiatric disorders, and meets common standards for psychiatric "caseness." This disorder identifies children with severe levels of both emotional and behavioral dysregulation.

Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.

Childhood trauma can have a profound effect on adolescent development, with a lifelong impact on physical and mental health and development. Through a review of current research on the impact of traumatic stress on adolescence, this article provides a framework for adolescent health professionals in pediatrics and primary care to understand and assess the sequelae of traumatic stress, as well as up-to-date recommendations for evidence-based treatment. We first review empirical evidence for critical windows of neurobiological impact of traumatic stress, and then we discuss the connection between these neurobiological effects and posttraumatic syndromes, including posttraumatic stress disorder, depression, aggressive behavior, and psychosis. This article concludes by considering the implications of this current research for clinical assessment and treatment in pediatric and primary care settings.

The present study is the first to assess whether the neural correlates of cognitive control processes differ in adults with and without a behaviorally inhibited temperament during early childhood. Adults with and without childhood behavioral inhibition completed an emotional conflict task while undergoing functional magnetic resonance imaging scanning. While no group differences in behavior were observed, adults with childhood behavioral inhibition, relative to adults without childhood behavioral inhibition, exhibited greater dorsomedial prefrontal cortex activity during conflict detection and greater putamen activity during conflict adaptation. Lifetime psychopathology predicted behavioral, but not brain-related, differences in conflict adaptation. These data suggest that the brain regions underlying cognitive control processes are differentially influenced by childhood behavioral inhibition, and may be differently related to psychopathology.

OBJECTIVES: Previous epidemiological studies have found lower mood, anxiety, and substance use disorder prevalence in Black Americans, in general, compared with White Americans. We estimated the prevalence and persistence of psychiatric disorders in African Americans, Caribbean Blacks, and non-Hispanic Whites. METHODS: We drew data from wave 1 (2001-2002) of the National Epidemiological Survey of Alcohol and Related Conditions, a nationally representative sample of US adults, which included 7529 African Americans, 469 Caribbean Blacks, and 24 502 non-Hispanic Whites. RESULTS: Blacks had equal or lower prevalence than Whites of lifetime (adjusted odds ratio [AOR] =0.6 for African Americans; 0.3 for Caribbean Blacks) and 12-month (AOR =0.7 for African Americans; 0.4 for Caribbean Blacks) Axis I psychiatric disorders, but higher prevalence of several personality disorders. Among Blacks, Caribbean Blacks had higher prevalence of 12-month psychotic disorders and lower lifetime prevalence of major depressive disorder, alcohol dependence, and drug abuse than African Americans. There were no differences in persistence of disorders between Caribbean Blacks and African Americans. CONCLUSIONS: This study yielded new data on prevalence of mental disorders in these groups, which has important implications for clinical work with US Blacks.

BACKGROUND: Parents of children with autism spectrum disorders (ASDs) are at risk for higher stress levels than parents of children with other developmental disabilities and typical development. Recent advances in early diagnosis have resulted in younger children being diagnosed with ASDs but factors associated with parent stress in this age group are not well understood. AIMS: The present study examined parenting-related stress and psychological distress in mothers of toddlers with ASD, developmental delay without ASD (DD), and typical development. The impact of child problem behavior and daily living skills on parenting-stress and psychological distress were further investigated. METHODS: Participants were part of a larger research study on early ASD intervention. RESULTS: Parent self-report of parenting-related stress and psychological distress was utilized. Parents of toddlers with ASD demonstrated increased parenting-related stress compared with parents of toddlers with DD and typical development. However, psychological distress did not differ significantly between the groups. Child behavior problems, but not daily living skills emerged as a significant predictor of parenting-related stress and psychological distress. This was true for both mothers of children with ASD and DD. CONCLUSIONS: These finding suggest that parents' abilities to manage and reduce behavior problems is a critical target for interventions for young children with ASD and DD in order to improve child functioning and decrease parenting-related stress.

BACKGROUND: One strategy to address health problems related to insufficient physical activity is to examine modifiable neighborhood characteristics associated with active transportation. PURPOSE: The aim of this study is to evaluate whether neighborhoods with more aesthetic amenities (sidewalk cafes, street trees, and clean sidewalks) and fewer safety hazards (pedestrian-auto fatalities and homicides) are associated with active transportation. METHODS: The 2003 Community Health Survey in New York City, which asked about active transportation (walking or bicycling >10 blocks) in the past 30 days, was linked to ZIP-code population census and built environment characteristics. Adjusted associations were estimated for dichotomous (any active transportation versus none) and continuous (trip frequency) active transportation outcomes. RESULTS: Among 8,034 adults, those living near sidewalk cafes were 10 % more likely to report active transportation (p = 0.01). Homicide rate was associated with less frequent active transportation among those reporting any active transportation (p = 0.002). CONCLUSIONS: Investments in aesthetic amenities or homicide prevention may help to promote active transportation.