Faculty Bibliography

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

The current study examines whether risk factors associated with child externalizing behavior symptoms differ between two similar low-income urban communities, using baseline parent data of 154 African American youth (ages 9-15) participating in the Collaborative HIV-Prevention and Adolescent Mental Health Project (CHAMP) family program. Separate multiple regression analyses of each city sample indicated that greater child externalizing symptoms were associated with increasing parenting hassles for New York families (n = 46), but greater parent mental health symptoms for participants in Chicago (n = 108). Understanding such distinctions between communities is an important first step towards tailoring services to unique community needs.

A long-standing problem in clinical research is distinguishing drug treated subjects that respond due to specific effects of the drug from those that respond to non-specific (or placebo) effects of the treatment. Linear mixed effect models are commonly used to model longitudinal clinical trial data. In this paper we present a solution to the problem of identifying placebo responders using an optimal partitioning methodology for linear mixed effects models. Since individual outcomes in a longitudinal study correspond to curves, the optimal partitioning methodology produces a set of prototypical outcome profiles. The optimal partitioning methodology can accommodate both continuous and discrete covariates. The proposed partitioning strategy is compared and contrasted with the growth mixture modelling approach. The methodology is applied to a two-phase depression clinical trial where subjects in a first phase were treated openly for 12 weeks with fluoxetine followed by a double blind discontinuation phase where responders to treatment in the first phase were randomized to either stay on fluoxetine or switched to a placebo. The optimal partitioning methodology is applied to the first phase to identify prototypical outcome profiles. Using time to relapse in the second phase of the study, a survival analysis is performed on the partitioned data. The optimal partitioning results identify prototypical profiles that distinguish whether subjects relapse depending on whether or not they stay on the drug or are randomized to a placebo.

Objective: Atomoxetine is a nonstimulant medication for treating child, adolescent, and adult ADHD. This meta-analysis compared the effects in younger and older adults. Method: A post hoc analysis was conducted using data from two double-blind, placebo-controlled clinical trials. Data from patients aged 18-25 years were compared with data from patients older than 25 years. Results: In younger adults (mean age = 21.7), atomoxetine produces greater improvement than placebo on the Conners' Adult ADHD Rating Scale's total ADHD symptom score (p = .041, effect size = .797) and the clinical global impressions severity (p = .006, effect size = 1.121). In older adults (mean age = 43.4 years), atomoxetine also produces significant benefit on the CAARS-Inv:SV (p < .001, effect size = .326) and CGI-ADHD-S (p < .001, effect size = .346). The study findings reveal response rates to be 56.4% and 47.8% for the younger and older adults, respectively (p = .188). Tolerability is similar although older adults reported more sexual side effects. Conclusion: Younger and older adults show similar improvements at endpoint. The effect size is higher in younger adults, but this is due primarily to greater variability of response in older patients

CONTEXT: Controversy surrounds the diagnostic categorization of generalized anxiety disorder (GAD). OBJECTIVES: To examine the incidence, comorbidity, and risk patterns for anxiety and depressive disorders and to test whether developmental features of GAD more strongly support a view of this condition as a depressive as opposed to an anxiety disorder. DESIGN: Face-to-face, 10-year prospective longitudinal and family study with as many as 4 assessment waves. The DSM-IV Munich Composite International Diagnostic Interview was administered by clinically trained interviewers. SETTING: Munich, Germany. PARTICIPANTS: A community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34 years at last follow-up. MAIN OUTCOME MEASURES: Cumulative incidence of GAD, other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic disorder), and depressive disorders (major depressive disorder, and dysthymia). RESULTS: Longitudinal associations between GAD and depressive disorders are not stronger than those between GAD and anxiety disorders or between other anxiety and depressive disorders. Survival analyses reveal that the factors associated with GAD overlap more strongly with those specific to anxiety disorders than those specific to depressive disorders. In addition, GAD differs from anxiety and depressive disorders with regard to family climate and personality profiles. CONCLUSIONS: Anxiety and depressive disorders appear to differ with regard to risk constellations and temporal longitudinal patterns, and GAD is a heterogeneous disorder that is, overall, more closely related to other anxiety disorders than to depressive disorders. More work is needed to elucidate the potentially unique aspects of pathways and mechanisms involved in the etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by cross-sectional features and diagnostic comorbidity patterns, minimizes the importance of longitudinal data on risk factors and symptom trajectories.