Faculty Bibliography

OBJECTIVE: Children with attention-deficit/hyperactivity disorder often have varying needs for coverage of their symptoms throughout the day. The objectives of this study were to determine the efficacy, duration of action, and safety of methylphenidate transdermal system worn for variable times by children (ages 6-12) diagnosed with ADHD. METHOD: Methylphenidate dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an Analog Classroom setting during a randomized, placebo-controlled, double-blind, three-way crossover phase. The main efficacy measures were the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and the Permanent Product Measure of Performance math test. RESULTS: All of the efficacy measures indicated that 4- and 6-hour wear times improved ADHD symptoms and that medication effects on the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and Permanent Product Measure of Performance math test decreased between 2 and 4 hours after patch removal. The majority of adverse events were transient and mild to moderate in severity. CONCLUSIONS: These findings suggest that the duration of medication effect is related to the wear time of the patch and may be tailored to accommodate the schedules of patients

Fear responses can be eliminated through extinction, a procedure involving the presentation of fear-eliciting stimuli without aversive outcomes. Extinction is believed to be mediated by new inhibitory learning that acts to suppress fear expression without erasing the original memory trace. This hypothesis is supported mainly by behavioral data demonstrating that fear can recover following extinction. However, a recent report by Myers and coworkers suggests that extinction conducted immediately after fear learning may erase or prevent the consolidation of the fear memory trace. Since extinction is a major component of nearly all behavioral therapies for human fear disorders, this finding supports the notion that therapeutic intervention beginning very soon after a traumatic event will be more efficacious. Given the importance of this issue, and the controversy regarding immediate versus delayed therapeutic interventions, we examined two fear recovery phenomena in both rats and humans: spontaneous recovery (SR) and reinstatement. We found evidence for SR and reinstatement in both rats and humans even when extinction was conducted immediately after fear learning. Thus, our data do not support the hypothesis that immediate extinction erases the original memory trace, nor do they suggest that a close temporal proximity of therapeutic intervention to the traumatic event might be advantageous

To enhance understanding of neuropsychological processing underlying chemosensory event-related potentials (CSERPs), the objective of the present study was to compare CSERPs with auditory (AERPs) and visual event-related potentials (VERPs), and to approach the question of similarities in neuropsychological processing by means of correlation and cluster analyses. A multisensory ERP protocol was used, in which olfactory/chemosomatosensory (pyridine), auditory (1000-Hz tone) and visual (white circle) stimuli were presented in a pseudo-randomized sequence to 18 young, healthy adults. The results show (1) a morphological relation between P2 and P3 components that is different for the chemosensory than for the auditory and visual modalities, (2) a relatively weak association between the chemosensory and auditory/visual modalities for P3 in terms of both correlation and cluster, and (3) a P2/P3 cluster for the chemosensory but not auditory or visual modality. This supports the claim that the chemosensory P2 and P3 components reflect similar neuropsychological processes.

Recent studies suggest a possible comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity. To gain insight into this potential association, we performed a systematic review of the literature excluding case reports, non-empirical studies, and studies not using ADHD diagnostic criteria. Empirically based evidence suggests that obese patients referred to obesity clinics may present with higher than expected prevalence of ADHD. Moreover, all reviewed studies indicate that subjects with ADHD are heavier than expected. However, data on the prevalence of obesity in subjects with ADHD are still limited. As for the mechanisms underlying the potential association between ADHD and obesity, ADHD might lead to obesity via abnormal eating behaviors, impulsivity associated with binge eating might contribute to ADHD in obese patients, or, alternatively, both obesity and ADHD might be the expression of common underlying neurobiological dysfunctions, at least in a subset of subjects. In patients with obesity and ADHD, both conditions might benefit from common therapeutic strategies. Further empirically based studies are needed to understand the potential comorbidity between obesity and ADHD, as well as the possible mechanisms underlying this association. This might allow a more appropriate clinical management and, ultimately, a better quality of life for patients with both obesity and ADHD.

OBJECTIVE: To examine the validity of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS), a new observational method for assessing preschool disruptive behavior. METHOD: A total of 327 behaviorally heterogeneous preschoolers from low-income environments comprised the validation sample. Parent and teacher reports were used to identify children with clinically significant disruptive behavior. The DB-DOS assessed observed disruptive behavior in two domains, problems in Behavioral Regulation and Anger Modulation, across three interactional contexts: Examiner Engaged, Examiner Busy, and Parent. Convergent and divergent validity of the DB-DOS were tested in relation to parent and teacher reports and independently observed behavior. Clinical validity was tested in terms of criterion and incremental validity of the DB-DOS for discriminating disruptive behavior status and impairment, concurrently and longitudinally. RESULTS: DB-DOS scores were significantly associated with reported and independently observed behavior in a theoretically meaningful fashion. Scores from both DB-DOS domains and each of the three DB-DOS contexts contributed uniquely to discrimination of disruptive behavior status, concurrently and predictively. Observed behavior on the DB-DOS also contributed incrementally to prediction of impairment over time, beyond variance explained by meeting DSM-IV disruptive behavior disorder symptom criteria based on parent/teacher report. CONCLUSIONS: The multidomain, multicontext approach of the DB-DOS is a valid method for direct assessment of preschool disruptive behavior. This approach shows promise for enhancing accurate identification of clinically significant disruptive behavior in young children and for characterizing subtypes in a manner that can directly inform etiological and intervention research

OBJECTIVE: To examine the reliability of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS), a new observational method for assessing preschool disruptive behavior. METHOD: The DB-DOS is a structured clinic-based assessment designed to elicit clinically salient behaviors relevant to the diagnosis of disruptive behavior in preschoolers. Child behavior is assessed in three interactional contexts that vary by partner (parent versus examiner) and level of support provided. Twenty-one disruptive behaviors are coded within two domains: problems in Behavioral Regulation and problems in Anger Modulation. A total of 364 referred and nonreferred preschoolers participated: interrater reliability and internal consistency were assessed on a primary sample (n = 335) and test-retest reliability was assessed in a separate sample (n = 29). RESULTS: The DB-DOS demonstrated good interrater and test-retest reliability. Confirmatory factor analysis demonstrated an excellent fit of the DB-DOS multidomain model of disruptive behavior. CONCLUSIONS: The DB-DOS is a reliable observational tool for clinic-based assessment of preschool disruptive behavior. This standardized assessment method holds promise for advancing developmentally sensitive characterization of preschool psychopathology

OBJECTIVE: Extensive work implicates abnormal amygdala activation in emotional facial expression processing in adults with callous-unemotional traits. However, no research has examined amygdala response to emotional facial expressions in adolescents with disruptive behavior and callous-unemotional traits. Moreover, despite high comorbidity of callous-unemotional traits and attention deficit hyperactivity disorder (ADHD), no research has attempted to distinguish neural correlates of pediatric callous-unemotional traits and ADHD. METHOD: Participants were 36 children and adolescents (ages 10-17 years); 12 had callous-unemotional traits and either conduct disorder or oppositional defiant disorder, 12 had ADHD, and 12 were healthy comparison subjects. Functional MRI was used to assess amygdala activation patterns during processing of fearful facial expressions. Patterns in the callous-unemotional traits group were compared with those in the ADHD and comparison groups. RESULTS: In youths with callous-unemotional traits, amygdala activation was reduced relative to healthy comparison subjects and youths with ADHD while processing fearful expressions, but not neutral or angry expressions. Functional connectivity analyses demonstrated greater correlations between the amygdala and the ventromedial prefrontal cortex in comparison subjects and youths with ADHD relative to those with callous-unemotional traits. Symptom severity in the callous-unemotional traits groups was negatively correlated with connectivity between amygdala and ventromedial prefrontal cortex. CONCLUSIONS: This is the first study to demonstrate reduced amygdala responsiveness in youths with callous-unemotional traits. These findings support the contention that callous and unemotional personality traits are associated with reduced amygdala response to distress-based social cues.

Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p </= 0.001). No changes in sexual functioning were detected. Significant improvement was also noted on the self-report measures of depressive symptoms. Sildenafil citrate might have an antidepressant effect on late onset DD, that is not attributable to improvement in erectile function. Possible explanations for this effect are offered. Larger placebo controlled studies are warranted

This investigation examined the preliminary efficacy of an integrated cognitive-behavioral parent-training protocol for six families of separation-anxious children (7 to 10 years of age) using a multiple baseline design across participants. Although families were assessed on child, parent, and clinician ratings at pre- and posttreatment as well as 6-month follow-up, only parents received education and training. Although the parent-training protocol was largely effective and treatment gains were maintained at 6-month follow-up, only those child participants whose parents experienced clinically significant improvement on parental process measures (i.e., enhanced efficacy or satisfaction, reduced stress) achieved high end-state functioning. Implications regarding the importance of individualized family-based interventions for treating anxious youth are discussed.

We examined the risk and protective factors and mental health problems of 105 low SES, urban adolescents whose mothers were coping with alcohol abuse and other drug problems. Approximately half of the mothers were also HIV-infected. As hypothesized, there were few differences between adolescents of HIV-infected and HIV-uninfected mothers in background characteristics, mental health issues and current substance use risk behaviors. In addition to maternal substance abuse, youth in both groups experienced similar risk factors including early foster care placement and high levels of maltreatment. Current patterns of emerging risk behaviors were evident among youth in both groups as well as signs of resiliency including high levels of school attendance. These results underscore the importance of interventions for youth of substance abusing mothers, particularly those living in urban poverty.