Faculty Bibliography

Objective: The study compared the efficacy of 2 behavioral interventions to ameliorate organization, time management, and planning (OTMP) difficulties in 3rd- to 5th-grade children with attention-deficit/hyperactivity disorder (ADHD). Method: In a dual-site randomized controlled trial, 158 children were assigned to organizational skills training (OST; N = 64); PATHKO, a performance-based intervention that precluded skills training (N = 61); or a wait-list control (WL, N = 33). Treatments were 20 individual clinic-based sessions over 10-12 weeks. OST involved skills building provided primarily to the child. PATHKO trained parents and teachers to reinforce children contingently for meeting end-point target goals. Primary outcomes were the Children's Organizational Skills Scales (COSS-Parent, COSS-Teacher). Other relevant functional outcomes were assessed. Percentage of participants no longer meeting inclusion criteria for OTMP impairments informed on clinical significance. Assessments occurred at post-treatment, 1-month post-treatment, and twice in the following school year. Results: OST was superior to WL on the COSS-P (Cohen's d = 2.77; p < .0001), COSS-T (d = 1.18; p < .0001), children's COSS self-ratings, academic performance and proficiency, homework, and family functioning. OST was significantly better than PATHKO only on the COSS-P (d = 0.63; p < .005). PATHKO was superior to WL on most outcomes but not on academic proficiency. Sixty percent of OST and PATHKO participants versus 3% of controls no longer met OTMP inclusion criteria. Significant maintenance effects were found for both treatments. Conclusions: Two distinct treatments targeting OTMP problems in children with ADHD generated robust, sustained functional improvements. The interventions show promise of clinical utility in children with ADHD and organizational deficits. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

RATIONALE: Understanding factors that adversely impact asthma management is imperative to enhance pediatric asthma. While family functioning has been found to be associated with medication adherence, its relationship to other aspects of asthma management has not been studied. Moderate levels of asthma-related anxiety are associated with optimal asthma management in adults; this has yet to be studied in youth. This novel study tested whether family functioning and asthma-related anxiety predict prevention and management behaviors and perceived asthma responsibility among urban early adolescents. METHODS: 386 early adolescents (mean age=12.8; 56% male; 49% Hispanic; 34% African American) with persistent, uncontrolled asthma from 23 NYC public middle schools reported steps they take to prevent symptom onset and manage symptoms once they begin, and completed the Asthma Responsibility Questionnaire, the Youth Asthma-related Anxiety Scale, and validated measures assessing family functioning (i.e., warmth, communication, problem-solving, and conflict). We assessed whether the relationships between the outcomes (prevention, management, and responsibility) and predictors (asthma-related anxiety and family functioning) are non-linear using generalized additive models (GAM) controlling for cohort, asthma severity, age and gender. If there was no evidence for non-linearity, the linear relationships were evaluated using generalized mixed effects models for normal or Poisson data. RESULTS: There was no evidence for non-linearity with one exception mentioned below. Asthma responsibility was the construct most impacted by family functioning. Youth reported their caregiver is more responsible for asthma management if they also reported more communication with caregivers (p<.001), having warm/nurturing caregivers (p<.001), and less child-caregiver conflict (p<.001). Increased asthma-related anxiety was related to youth taking more steps to prevent (p<.001) and manage (p=.02) asthma. For prevention, the relationship was non-linear (df=2.4) - with anxiety above 2 (on a scale from 0-5), there was no additional increase in prevention steps. With increased asthma-related anxiety, youth felt they, not their caregivers, were more responsible for asthma management (p=0.015). CONCLUSIONS: Findings suggest a need for family-centered care to ensure caregivers remain connected to their early adolescent and do not transfer responsibility for managing asthma to their children prematurely. Also, clinicians should assess youths' anxiety as part of routine asthma care. When asthma-related anxiety is low, youth may benefit from increased awareness of the consequences of uncontrolled asthma. In contrast, when anxiety is elevated, clinicians should consider referring the family to a mental health provider to ensure the youth are not assuming responsibility prematurely as a means of coping with the anxiety

Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence. METHODS: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated. RESULTS: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures. CONCLUSIONS: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.

Background: Reductions in brain-derived neurotrophic factor (BDNF) have been implicated in the pathophysiology of Alzheimer's disease (AD). Nevertheless, the factors influencing central and peripheral BDNF levels are still poorly understood. Cerebral microvascular endothelial cells are known to be a major source of BDNF with a rate of production by far exceeding that of cortical neurons. Exposure of these cells to amyloid beta (Ab), results in cell death or injury with significant reductions in BDNF secretion. Moreover, in rodents, infusion of Ab40 into the carotid resulted in a disruption of endothelial cells, which was not observed with Ab42. Plasma Ab40 levels have also been associated with white matter hyperintense lesions (WMHI) on MRI scans in AD, an effect that may be mediated by the toxic effects of soluble Ab40 on small cerebral blood vessels and endothelial cells. Therefore, we hypothesized that concentrations of plasma Ab40, but not Ab42, would have a negative effect on plasma BDNF and on measures of white matter integrity as determined by Diffusion Tensor Imaging (DTI). Methods: To test this hypothesis, we examined BDNF and Ab levels in plasma from 119 subjects with intact cognition (no dementia and a Mini-Mental State Exam score of at least 28) and no gross MRI abnormalities other than white matter hyperintensities. Of these, 88 subjects also had BDNF in plasma determined. Results: Consistent with our prediction, Ab40 was inversely correlated with BDNF concentrations (P <.001), whereas Ab42 was independent (P = .231). Fractional anisotropy (FA; a measure of white matter integrity in DTI) was also inversely correlated with Ab40 (P = .001) and so was performance in delayed recall (P = .029). Conclusions: In cognitively intact individuals, circulating Ab40 results in reduction in plasma BDNF, white matter integrity (FA), and memory performance. As such, it may have prognostic significance

The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

Correctly identifying voxels or regions of interest (ROI) that actively respond to a given stimulus is often an important objective/step in many functional magnetic resonance imaging (fMRI) studies. In this article, we study a nonparametric method to detect active voxels, which makes minimal assumption about the distribution of blood oxygen level-dependent (BOLD) signals. Our proposal has several interesting features. It uses time lagged correlation to take into account the delay in response to the stimulus, due to hemodynamic variations. We introduce an input permutation method (IPM), a type of block permutation method, to approximate the null distribution of the test statistic. Also, we propose to pool the permutation-derived statistics of preselected voxels for a better approximation to the null distribution. Finally, we control multiple testing error rate using the local false discovery rate (FDR) by Efron [Correlation and large-scale simultaneous hypothesis testing. J Am Stat Assoc 102 (2007) 93-103] and Park et al. [Estimation of empirical null using a mixture of normals and its use in local false discovery rate. Comput Stat Data Anal 55 (2011) 2421-2432] to select the active voxels.

BACKGROUND: It has been proposed that posttraumatic stress disorder (PTSD) patients who experience significant dissociation upon exposure to traumatic reminders may do less well in trauma-focused therapies. We explored whether a sequenced two-component treatment in which an emotion regulation skills training module preceding exposure would improve outcomes for those with significant dissociation. METHODS: Analyses were conducted on data from an RCT in which 104 women with PTSD related to childhood abuse were assigned to one of three treatment conditions: Skills Training in Affective and Interpersonal Regulation (STAIR) followed by Narrative Story Telling (NST; STAIR/NST), STAIR followed by supportive counseling (SC; STAIR/SC), or SC followed by NST (SC/NST). RESULTS: Baseline dissociation was associated with differential outcome such that at low levels of dissociation the three treatments were equally effective but at higher levels STAIR/NST resulted in greater reductions in dissociative symptoms. Level of baseline dissociation did not moderate the effect of the treatments on PTSD outcome. At all levels of baseline dissociation, STAIR/NST produced better PTSD outcome. At posttreatment, however, participants with high dissociation treated with STAIR/NST continued to improve during follow-up, those treated with STAIR/SC maintained gains, and those treated with SC/NST experienced loss of posttreatment PTSD symptom gains. CONCLUSIONS: The differential results observed among the treatments depending on severity of dissociation at baseline and at posttreatment suggest the potential clinical utility of identifying a dissociative subtype of PTSD and of the benefits of sequenced, phase-oriented treatment approaches.

OBJECTIVE: Major depressive disorder is common in the elderly, and symptoms are often not responsive to conventional antidepressant treatment, especially in the long term. Soluble oligomeric and aggregated forms of amyloid beta peptides, especially amyloid beta 42, impair neuronal and synaptic function. Amyloid beta 42 is the main component of plaques and is implicated in Alzheimer's disease. Amyloid beta peptides also induce a depressive state in rodents and disrupt major neurotransmitter systems linked to depression. The authors assessed whether major depression was associated with CSF levels of amyloid beta, tau protein, and F2-isoprostanes in elderly individuals with major depressive disorder and age-matched nondepressed comparison subjects. METHOD: CSF was obtained from 47 cognitively intact volunteers (major depression group, N=28; comparison group, N=19) and analyzed for levels of soluble amyloid beta, total and phosphorylated tau proteins, and isoprostanes. RESULTS: Amyloid beta 42 levels were significantly lower in the major depression group relative to the comparison group, and amyloid beta 40 levels were lower but only approaching statistical significance. In contrast, isoprostane levels were higher in the major depression group. No differences were observed in total and phosphorylated tau proteins across conditions. Antidepressant use was not associated with differences in amyloid beta 42 levels. CONCLUSIONS: Reduction in CSF levels of amyloid beta 42 may be related to increased brain amyloid beta plaques or decreased soluble amyloid beta production in elderly individuals with major depression relative to nondepressed comparison subjects. These results may have implications for our understanding of the pathophysiology of major depression and for the development of treatment strategies.