Faculty Bibliography

Compared two groups of children with anxiety disorders served at a single mental health clinic whose referral source differed: private referrals (i.e., parent/legal guardian initiated) and public referrals (e.g., via state contracts--Departments of Health and Education, juvenile justice system). Comparisons were made across three domains of variables: (a) symptoms/diagnoses, (b) functioning, and (c) environments. Few symptom differences emerged. However, large differences were evident for contextual variables like family income and life stressors. Overall, the pattern of differences point to possible directions for adaptation of treatments for use with children with anxiety disorders served in public mental health systems.

The social cognition and perception-action literatures are largely separate, both conceptually and empirically. However, both areas of research emphasize infants' emerging abilities to use available information--social and perceptual information, respectively--for making decisions about action. Borrowing methods from both research traditions, this study examined whether 18-month-old infants incorporate both social and perceptual information in their motor decisions. The infants' task was to determine whether to walk down slopes of varying risk levels as their mothers encouraged or discouraged walking. First, a psychophysical procedure was used to determine slopes that were safe, borderline, and risky for individual infants. Next, during a series of test trials, infants received mothers' advice about whether to walk. Infants used social information selectively: They ignored encouraging advice to walk down risky slopes and discouraging advice to avoid safe slopes, but they deferred to mothers' advice at borderline slopes. Findings indicate that 18-month-old infants correctly weigh competing sources of information when making decisions about motor action and that they rely on social information only when perceptual information is inadequate or uncertain.

Transition in pediatric transplant recipients consists of both a physical shift in medical care location as well as a transition in health care responsibilities from caregivers to patients. The purpose of the present study was to test the feasibility of a pilot intervention aiming to facilitate the transition in health care responsibilities from caregivers to patients while patients are still receiving pediatric services. Twenty-two patients were enrolled in a two-session educational protocol aiming to facilitate transition of responsibility. Patients were recruited from an outpatient transplant clinic. Ten were referred because of suspected difficulty in transitioning of care, and 12 were consecutively recruited without any specific a priori concerns. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, and ALT levels were the medical outcome measures. Complete data are available for 20 patients. Mean ALT levels improved after the follow-up period. For referred patients, adherence and ALT levels improved. Standard deviation of tacrolimus decreased from 3.33 to 2.23, t = 2.52, p = 0.04. Mean ALT decreased from 120.33 to 63.99, t = 3.01, p = 0.01. Maximal ALT values decreased overall from 284.10 to 101.20, t = 2.61, p = 0.03. Our findings suggest that targeted education regarding transition in responsibility for adolescents' own health care is feasible in the outpatient environment and may assist families who are facing this potentially challenging process. A randomized, controlled study with a substantial number of enrolled patients is needed to establish the efficacy of this or other approaches

Estrogenic effects involve interactions between estrogen receptors (ERs), response elements, and nuclear proteins. It is hypothesized that interaction between ER and NF-kappa B may affect the regulation of responsive genes. Electrophoretic mobility shift assay (EMSA) was performed to assess if the interaction of ERs and NF- kappaB affect their respective DNA-binding activities, and alkaline phosphatase assay was done to evaluate estrogenic activity. EMSA revealed that ERs inhibit DNA-binding of p50 and p65, whereas p50 did not impair ER alpha binding. Stimulation with estradiol inhibited DNA binding of NF-kappaB in ERalpha-transfected endometrial stromal cells (ESCs). Moreover, activation of NF-kappaB significantly decreased estrogen responsiveness of Ishikawa cells and ERalpha-transfected ESC. Our results suggest that ERs downregulate NF-kappaB-dependent gene activation by directly preventing DNA binding. However, NF-kappaB-mediated inhibition of ER-dependent gene activation may be carried out indirectly rather than through a direct inhibition of ER-DNA binding. These findings offer new insight into the specific role of ERalpha and could eventually help in developing therapeutics for endometriosis.

CONTEXT: Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety. OBJECTIVE: To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis. MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces. RESULTS: When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects. CONCLUSIONS: Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.

OBJECTIVE: Although serotonin reuptake inhibitors (SRIs) are approved for the treatment of obsessive-compulsive disorder (OCD), most OCD patients who have received an adequate SRI trial continue to have clinically significant OCD symptoms. The purpose of this study was to examine the effects of augmenting SRIs with exposure and ritual prevention, an established cognitive-behavioral therapy (CBT) for OCD. METHOD: A randomized, controlled trial was conducted at two academic outpatient clinics to compare the effects of augmenting SRIs with exposure and ritual prevention versus stress management training, another form of CBT. Participants were adult outpatients (N=108) with primary OCD and a Yale-Brown Obsessive Compulsive Scale total score > or = 16 despite a therapeutic SRI dose for at least 12 weeks prior to entry. Participants received 17 sessions of CBT (either exposure and ritual prevention or stress management training) twice a week while continuing SRI pharmacotherapy. RESULTS: Exposure and ritual prevention was superior to stress management training in reducing OCD symptoms. At week 8, significantly more patients receiving exposure and ritual prevention than patients receiving stress management training had a decrease in symptom severity of at least 25% (based on Yale-Brown Obsessive Compulsive Scale scores) and achieved minimal symptoms (defined as a Yale-Brown Obsessive Compulsive Scale score < or = 12). CONCLUSIONS: Augmentation of SRI pharmacotherapy with exposure and ritual prevention is an effective strategy for reducing OCD symptoms. However, 17 sessions were not sufficient to help most of these patients achieve minimal symptoms

Previous studies have shown that medial prefrontal cortical regions, such as the anterior cingulate cortex (ACC), play a key role in the expression of remote spatial and contextual memory. To evaluate whether this role is conserved in hippocampal-independent tasks we trained mice in the conditioned taste aversion (CTA) paradigm. Lidocaine-induced inactivation of the ACC blocked the expression of CTA tested one month (remote), but not one day (recent), after conditioning with either a weak or strong unconditioned stimulus (US). These data suggest that the ACC may play a conserved role in remote memory, regardless of memory strength or content.

OBJECTIVE: The purpose of this study was to assess the effectiveness of a new manualized group Meta-Cognitive Therapy (MCT) for adults with ADHD that extends the principles and practices of cognitive-behavioral therapy to the development of executive self-management skills. METHOD: Thirty adults diagnosed with ADHD completed an 8- or 12-week program designed to target impairments in time management, organization, and planning skills. Treatment efficacy was measured using pre- and posttreatment self-report standardized measures (CAARS-S:L & Brown ADD Scales). RESULTS: General linear modeling revealed a robust significant posttreatment decline on the CAARS DSM-IV Inattentive symptom scale (p < .001) as well as improvement on the Brown ADD Scales (p < .001). CONCLUSION: The findings indicate that participants in the MCT program showed marked improvement with respect to core ADHD symptoms of inattention, as well as executive functioning skills, suggesting that this program has promise as a treatment for meta-cognitive deficits in adults with ADHD.

OBJECTIVE: To compare clinical responses of patients with pediatric bipolar disorder being treated with risperidone versus divalproex. METHODS: Medical records of outpatients younger than 18 years of age were reviewed to gather data on those who received risperidone or divalproex monotherapy for the treatment of bipolar disorder. Effectiveness was assessed using the Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales assigned by the treating clinician at visits during the initial 3 months of treatment with risperidone or divalproex. Change in CGI-S score over time was the primary outcome variable. The number of patients with a CGI-I score of < or = 2 at endpoint who did not discontinue the index medication because of adverse events was also compared. RESULTS: A total of 28 patients aged 5-14 years who were being treated for bipolar disorder were identified (risperidone n = 16; divalproex n = 12). Regression analysis of change in CGI-S scores revealed greater reductions in bipolar symptoms (p = 0.022) and a faster reduction in CGI-S scores (p = 0.016) in patients receiving risperidone than divalproex. A significantly shorter time to achieving a CGI-I score of < or = 2 was observed with risperidone than divalproex (26.8 +/- 20.7 days vs. 33.8 +/- 11.3 days; p = 0.048). However, the proportion of patients with a CGI-I score < or = 2 at endpoint was not significantly different (risperidone 69% versus divalproex 42%, p = 0.250). Three patients discontinued risperidone and 2 discontinued divalproex. Of these, none of the patients treated with risperidone and only 1 patient treated with divalproex discontinued treatment because of a documented adverse event. Risperidone was associated with significantly more weight gain then divalproex at 3 months (risperidone 2.46 +/- 1.16 kg versus divalproex 0.43 +/- 0.77 kg, p = 0.034). CONCLUSIONS: Patients receiving risperidone experienced a faster decrease in the severity of their bipolar symptoms, as measured by faster decreases in CGI-S scores, than did those who received divalproex. However, risperidone was also associated with significantly greater weight gain.