Faculty Bibliography

OBJECTIVE:Clinical observations have suggested therapeutic effects for omega-3 fatty acids (O3FA) in Tourette's disorder (TD), but no randomized, controlled trials have been reported. In a placebo-controlled trial, we examined the efficacy of O3FA in children and adolescents with TD.METHODS:Thirty-three children and adolescents (ages 6-18) with TD were randomly assigned, double-blind, to O3FA or placebo for 20 weeks. O3FA consisted of combined eicosapentaenoic acid and docosahexaenoic acid. Placebo was olive oil. Groups were compared by using (1) intent-to-treat design, with the last-observation-carried-forward controlling for baseline measures and attention-deficit/hyperactivity disorder via (a) logistic regression, comparing percentage of responders on the primary Yale Global Tic Severity Scale (YGTSS)-Tic and secondary (YGTSS-Global and YGTSS-Impairment) outcome measures and (b) analysis of covariance; and (2) longitudinal mixed-effects models.RESULTS:At end point, subjects treated with O3FA did not have significantly higher response rates or lower mean scores on the YGTSS-Tic (53% vs 38%; 15.6 +/- 1.6 vs 17.1 +/- 1.6, P > .1). However, significantly more subjects on O3FA were considered responders on the YGTSS-Global measure (53% vs 31%, P = .05) and YGTSS-Impairment measure (59% vs 25%, P < .05), and mean YGTSS-Global scores were significantly lower in the O3FA-treated group than in the placebo group (31.7 +/- 2.9 vs 40.9 +/- 3.0, P = .04). Obsessive-compulsive, anxiety, and depressive symptoms were not significantly affected by O3FA. Longitudinal analysis did not yield group differences on any of the measures.CONCLUSIONS:O3FA did not reduce tic scores, but it may be beneficial in reduction of tic-related impairment for some children and adolescents with TD. Limitations include the small sample and the possible therapeutic effects of olive oil.

Greater intra-subject variability (ISV) in response time is a heritable endophenotype of attention-deficit/hyperactivity disorder (ADHD). Spontaneous low frequency oscillations (LFO: 0.01-0.1 Hz) observed in brain functional magnetic resonance signals might account for such behavioral variability. Recently, we demonstrated that ISV in response time (RT) explained ratings of ADHD symptoms. Building on this finding, here we hypothesized that LFO in RT time series would explain these ratings, both independently and in addition to RT coefficient of variation (CV). To measure RT LFO, we applied Morlet wavelet transform to the previously collected RT data. Our community sample consisted of 98 children (including 66 boys, mean age 9.9 +/- 1.4 years), who completed four computer Tasks of Executive Control. Conners' Parent Rating Scale ratings were obtained. RT LFO of three tasks significantly explained ratings of inattention, hyperactivity and three global Conners' subscales. In addition, RT LFO during two tasks that included an inhibitory component increased the proportions of variance explained in subscales of both inattention and hyperactivity/impulsivity, beyond the effects of RT-CV. Three specific low frequency bands (Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz; Slow-3: 0.073-0.20 Hz) were strongly related to the ADHD scales. We conclude that RT LFO predict dimensional ratings of ADHD symptoms both independently and in addition to RTCV. Results suggest that frequency analyses are a suitable methodology to link behavioral responses to putative underlying physiological processes.

OBJECTIVES: To test the hypothesis that family intervention to promote effective parenting in early childhood affects obesity in preadolescence. METHODS: Participants were 186 minority youth at risk for behavior problems who enrolled in long-term follow-up studies after random assignment to family intervention or control condition at age 4. Follow-up Study 1 included 40 girls at familial risk for behavior problems; Follow-up Study 2 included 146 boys and girls at risk for behavior problems based on teacher ratings. Family intervention aimed to promote effective parenting and prevent behavior problems during early childhood; it did not focus on physical health. BMI and health behaviors were measured an average of 5 years after intervention in Study 1 and 3 years after intervention in Study 2. RESULTS: Youth randomized to intervention had significantly lower BMI at follow-up relative to controls (Study 1 P = .05; Study 2 P = .006). Clinical impact is evidenced by lower rates of obesity (BMI >/=95th percentile) among intervention girls and boys relative to controls (Study 2: 24% vs 54%, P = .002). There were significant intervention-control group differences on physical and sedentary activity, blood pressure, and diet. CONCLUSIONS: Two long-term follow-up studies of randomized trials show that relative to controls, youth at risk for behavior problems who received family intervention at age 4 had lower BMI and improved health behaviors as they approached adolescence. Efforts to promote effective parenting and prevent behavior problems early in life may contribute to the reduction of obesity and health disparities.

CONTEXT: Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. OBJECTIVE: To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. DESIGN: Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. SETTING: Participants were recruited through 12 university-based autism service providers into a genetic study of autism. PARTICIPANTS: A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. Main Outcome Measure Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. RESULTS: Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. CONCLUSIONS: Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function

Introduction. Youth as young as 11 are given responsibility to manage their asthma. Yet, little is known regarding early adolescents' asthma self-management behaviors. This study characterizes urban early adolescents' asthma self-management behaviors and perceived responsibility to manage asthma, exploring demographic differences and examining the relationship between asthma responsibility and disease management. Methods. About 317 Hispanic and African American/Black early adolescents (mean age = 12.71) with persistent, uncontrolled asthma reported prevention and symptom management steps, and responsibility for asthma care. We used Poisson, cumulative logistic, logistic, and linear mixed-effects regression models to assess the relationships among demographic predictors, prevention and management behaviors, and responsibility for asthma care. Results. Fifty percent took 7-9 prevention steps; few saw physicians when asymptomatic or took daily medication. When symptomatic, 92% used medication to treat symptoms and 56% sought medical attention. Controlling for asthma responsibility, fewer older youth reported observing how they feel when asthma is likely to start, observing symptom changes, or asking for help. More boys reported taking medication daily or upon trigger exposure. Controlling for age, gender, and race/ethnicity, those reporting more asthma responsibility were less likely to report taking management steps, seeking preventive care, asking for help, or going to a doctor/hospital for their asthma. Conclusions. Early adolescents' asthma self-management is suboptimal. With increasing age, they are less observant regarding their asthma and less likely to seek help. Although they perceive themselves to have greater responsibility for managing their asthma, early adolescents do less to care for their asthma, suggesting they are being given responsibility for asthma care prematurely

RATIONALE:As early as age 11 children begin to take responsibility for asthma self-management, yet very little is known about asthma management behaviors in early adolescents. In this study we characterize early adolescents' asthma prevention and management steps and their perceived responsibility; explore differences in asthma self-management and responsibility according to demographic characteristics; and investigate the role of perceived responsibility in prevention and management behaviors. METHODS:We utilized baseline data from a randomized controlled trial testing the efficacy of an asthma intervention. 317 African-American (41%) and Hispanic (59%) children (mean age=12.7) with persistent asthma answered 9 questions regarding prevention steps taken regularly (3-point Likert scale), 7 questions regarding steps taken to manage symptoms (yes/no), and the 10-item Asthma Responsibility Questionnaire (5-point Likert scale). Using generalized estimating equations, we modeled the total number of prevention and management steps taken and individual self-management items as a function of demographic characteristics, controlling for asthma severity. We then added responsibility to the model. Last we modeled asthma responsibility as a function of demographic characteristics controlling for severity. RESULTS:49% took 7-9 prevention steps; 31% took daily medication regularly; 34% did not take daily medication; only 24% saw a physician when asymptomatic. 61% took 6-7 management steps; 92% took medication, but only 26% asked for help. Older youth had lower odds of observing how they feel when asthma is likely to start (Odds ratio[OR]=0.82,p<0.05), observing symptoms to see if they improve or get worse (OR=0.71,p<0.05) and asking for help (OR=0.72,p<0.05). Boys had significantly higher odds of taking daily medication preventively (OR=1.52,p<0.05) and upon exposure to triggers (OR=1.62,p<0.05). Results were consistent when controlling for asthma severity and both asthma severity and responsibility. Controlling for age and asthma severity, early adolescents who reported taking more responsibility for managing their asthma were more likely to take fewer steps to manage their asthma once symptoms begin (Risk ratio=0.97,p<0.01), and had lower odds of seeking preventive care (OR=0.67,p<0.001), asking for help (OR=0.70, p<0.01), and going to a doctor or hospital to manage their asthma (OR=0.74,p<0.001); results were consistent when controlling for gender and race/ethnicity. CONCLUSIONS:Early adolescents' asthma self-management is suboptimal. Despite having persistent asthma, a minority took daily medication preventively or sought preventive medical care. With increasing age, children were less observant regarding their asthma and less likely to seek help. As early adolescents perceive themselves to have greater responsibility for managing their asthma, they have lower odds of taking certain self-management steps

This study examines the efficacy of ParentCorps among 4-year-old children (N = 171) enrolled in prekindergarten in schools in a large urban school district. ParentCorps includes a series of 13 group sessions for parents and children held at the school during early evening hours and facilitated by teachers and mental health professionals. ParentCorps resulted in significant benefits on effective parenting practices and teacher ratings of child behavior problems in school. Intervention effects were of similar magnitude for families at different levels of risk and for Black and Latino families. The number of sessions attended was related to improvements in parenting. Study findings support investment in and further study of school-based family interventions for children from underserved, urban communities

This study was designed to understand molecular and cellular mechanisms underlying aggressive behaviors in mice exposed to repeated interactions in their homecage with conspecifics. A resident-intruder procedure was employed whereby two males were allowed to interact for 10 min trials, and aggressive and/or submissive behaviors (e.g., degree of attacking, biting, chasing, grooming, rearing, or upright posture) were assessed. Following 10 days of behavioral trials, brains were removed and dissected into specific regions including the cerebellum, frontal cortex, hippocampus, midbrain, pons, and striatum. Gene expression analysis was performed using real-time quantitative polymerase-chain reaction (qPCR) for catechol-O-methyltransferase (COMT) and tyrosine hydroxylase (TH). Compared to naive control mice, significant up regulation of COMT expression of residents was observed in the cerebellum, frontal cortex, hippocampus, midbrain, and striatum; in all of these brain regions the COMT expression of residents was also significantly higher than that of intruders. The intruders also had a significant down regulation (compared to naive control mice) within the hippocampus, indicating a selective decrease in COMT expression in the hippocampus of submissive subjects. Immunoblot analysis confirmed COMT up regulation in the midbrain and hippocampus of residents and down regulation in intruders. qPCR analysis of TH expression indicated significant up regulation in the midbrain of residents and concomitant down regulation in intruders. These findings implicate regionally- and behaviorally-specific regulation of COMT and TH expression in aggressive and submissive behaviors. Additional molecular and cellular characterization of COMT, TH, and other potential targets is warranted within this animal model of aggression

Introduction: An important goal of ongoing Alzheimer's disease (AD) research is to identify markers that allow one to predict risk for the development of this type of dementia in cognitively intact elderly. Known cognitive changes associated with AD, possibly reflecting hippocampal pathology, include a worse recall of primacy items and better immediate recall of items learned at the end of a list compared to the middle (recency effect). Aims: The aim of our study was to examine whether learning and recall of primacy and recency words predicted future decline in intact elderly subjects. Methods: Individuals with MMSE of 28 or over at baseline were included in the study. Of these, 211 had at least two successive cognitive evaluations; mean age at baseline was 69.5 (SD=8.0). We regressed MMSE decline on baseline Auditory-Verbal Learning Test (AVLT) memory measures, focusing especially on learning and recall of primacy and recency words, and controlling for baseline age, time since baseline and other variables. Results: Worse learning/delayed recall of primacy words on AVLT trials consistently predicted greater subsequent cognitive decline. Additionally, this effect was stronger among older subjects than among younger ones. APOE e4, a well established genetic risk factor for late-onset AD, was not a significant predictor of MMSE decline in this sample. Conclusions: Decreased learning and poorer recall of primacy words in the AVLT is a predictor of decline in healthy elderly individuals, and future studies should examine if decreased learning and recall can predict conversion to AD