Faculty Bibliography

In the last three decades there has been ample research to demonstrate that instituting Multisystemic Therapy for serious juvenile offenders, keeping them in the community with intensive intervention, can significantly reduce recidivism. When there is recidivism, it is less severe than in released incarcerated juveniles. Multisystemic Therapy provides 24 h available parental guidance, family therapy, individual therapy, group therapy, educational support and quite importantly a change of peer group. In New York City, there is the new mandate through the Juvenile Justice Initiative to implement interventions to keep juvenile offenders in the community rather than sending them to be incarcerated. However, this paper aims to examine how teaching prosocial values in early childhood can reduce the incidence of first-time juvenile delinquency. Programs such as the Perry School Project will be discussed to demonstrate that although somewhat expensive, these innovative programs nonetheless are quite cost-effective as the cost to society of adjudication, incarceration and victim damages are significantly greater. Along with teaching prosocial 0020 values, there has been renewed interest in early identification of youth at risk for developing Antisocial Personality Disorder. An update is given on the status of both promising approaches in early intervention to prevent serious juvenile delinquency and hence adult criminality.

The VUKA family program is one of the only evidence-based interventions to promote positive psychosocial outcomes in South African HIV-infected pre- and early adolescents and their families. In this paper, we discuss the collaborative process by which a multidisciplinary team of clinicians, researchers, counselors, and artists/educators and families adapted and developed VUKA for this population using community-based participatory research methods. We describe the intervention and explore lessons learned that may be applicable across contexts related to international collaboration and adapting evidence-based interventions so that they are likely to be acceptable, feasible, and effective in a given setting and country context.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (1H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD. METHODS: We studied 75 subjects from the largest multigenerational pedigree in the world ( approximately 5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two-dimensional 1H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to 1H-MRS data while controlling for age, educational level, and sex. RESULTS: We found that (1) the combination of LPPGM Cho/Cr <0.165 and RPPGM Glx/Cr >1.54 fully excluded carriers; (2) LPPGM Cho/Cr >0.165, RPPGM Glx/Cr <1.54, and left parietal white mater NAA/Cr >1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr >1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%. CONCLUSIONS: Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.

The goal of this study was to examine the impact of supplementing Trauma-focused Cognitive Behavioral Therapy (TF-CBT; Cohen et al., 2006) with evidence-based engagement strategies on foster parent and foster youth engagement in treatment, given challenges engaging foster parents in treatment. A randomized controlled trial of TF-CBT standard delivery compared to TF-CBT plus evidence-based engagement strategies was conducted with 47 children and adolescents in foster care and one of their foster parents. Attendance, engagement, and clinical outcomes were assessed 1 month into treatment, end of treatment, and 3 months post-treatment. Youth and foster parents who received TF-CBT plus evidence-based engagement strategies were more likely to be retained in treatment through four sessions and were less likely to drop out of treatment prematurely. The engagement strategies did not appear to have an effect on the number of canceled or no-show sessions or on treatment satisfaction. Clinical outcomes did not differ by study condition, but exploratory analyses suggest that youth had significant improvements with treatment. Strategies that specifically target engagement may hold promise for increasing access to evidence-based treatments and for increasing likelihood of treatment completion.

This article reviews the clinical features and neurochemical hypotheses of obsessive-compulsive disorder (OCD) with a focus on the serotonin system. In DSM-5, OCD was moved from the anxiety disorders to a new category of Obsessive-Compulsive and Related Disorders. OCD is a common, typically persistent disorder marked by intrusive and disturbing thoughts (obsessions) and repetitive behaviors (compulsions) that the person feels driven to perform. The preferential efficacy of serotonin reuptake inhibitors (SRIs) in OCD led to the so-called serotonin hypothesis. However, direct support for a role of serotonin in the pathophysiology (e.g., biomarkers in pharmacological challenge studies) of OCD remains elusive. A role of the glutamatergic system in OCD has been gaining traction based on imaging data, genomic studies and animal models of aberrant grooming behavior. These findings have spurred interest in testing the efficacy of medications that modulate glutamate function. A role of glutamate is compatible with circuit-based theories of OCD.

OBJECTIVE: To assess self-perceptions of social behavior among children treated for a brain tumor and comparison children. To investigate group differences in the accuracy of children's self-perceptions as measured by discrepancies between self and peer reports of social behavior and to understand if these phenomena differ by gender. METHOD: Self and peer reports of social behavior were obtained in the classrooms of 116 children who were treated for an intracranial tumor. Social behaviors were assessed using the Revised Class Play, which generates indices for 5 behavioral subscales: Leadership-popularity, Prosocial, Aggressive-disruptive, Sensitive-isolated, and Victimization. A child matched for gender, race, and age was selected from each survivor's classroom to serve as a comparison. Abbreviated IQ scores were obtained in participants' homes. RESULTS: Relative to comparison children, those who had undergone treatment for a brain tumor overestimated their level of Leadership-popularity and underestimated levels of Sensitive-isolated behaviors and Victimization by peers. Female survivors were more likely than male survivors to underestimate Sensitive-isolated behaviors and Victimization. CONCLUSION: Following treatment for a brain tumor, children (particularly girls) may be more likely than healthy children to underestimate peer relationship difficulties. These discrepancies should be considered when obtaining self-report from survivors and developing interventions to improve social functioning.

BACKGROUND: Due to the devastating late effects associated with cranial irradiation in young children with central nervous system (CNS) tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. OBJECTIVE: This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. METHODS: Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. RESULTS: Twenty-one survivors (medulloblastoma = 13, sPNET = 4, ATRT = 1, ependymoma = 3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included >/= grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years), dental (52%; 7.1 years), and no cases of secondary leukemia. Irradiation-free (vs. irradiated) survivors reported low rates of hypothyroidism (0/10 vs. 7/11; P = 0.004) and GH deficiency (2/10 vs. 8/11; P = 0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation was associated with these scores. CONCLUSIONS: Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow-up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.

The aim of this study was to investigate the temporal abilities of children treated by surgery for a malignant tumor in the cerebellum, both in the perception and the production of rhythm. Children with a diagnosed medulloblastoma and age-matched control children were tested in a rhythm discrimination task and a sensorimotor synchronization task. Their motor and cognitive capabilities were also assessed through a battery of age-adapted neuropsychological tests. The results did not show any significant difference in performance between groups for the discrimination task. On the contrary, children with cerebellar lesions produced longer and more variable inter-tap intervals (ITI) in their spontaneous motor tempo (SMT) than did the control children. However, the length and, to a lesser extent, the variability of their SMT decreased after a synchronization phase, when they had been instructed to tap in synchrony with a beep. During the synchronization task, the children with medulloblastoma succeeded to modify the length of their ITI in response to an auditory rhythm, although with better success when the inter-stimuli intervals (ISI) were shorter than when they were longer than the ITIs of their own SMT. Correlational analyses revealed that children's poorer synchronization performance was related to lower scores in neuropsychological tests assessing motor dexterity and processing speed.

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

Many techniques of functional data analysis require choosing a measure of distance between functions, with the most common choice being L2 distance. In this article we show that using a weighted L2 distance, with a judiciously chosen weight function, can improve the performance of various statistical methods for functional data, including k-medoids clustering, nonparametric classification, and permutation testing. Assuming a quadratically penalized (e.g., spline) basis representation for the functional data, we consider three nontrivial weight functions: design density weights, inverse-variance weights, and a new weight function that minimizes the coefficient of variation of the resulting squared distance by means of an efficient iterative procedure. The benefits of weighting, in particular with the proposed weight function, are demonstrated both in simulation studies and in applications to the Berkeley growth data and a functional magnetic resonance imaging data set.