Faculty Bibliography

The aim of this paper was to discuss the arguments for and against the use of atypical antipsychotics in children and adolescents with aggression, and provide recommendations for future research. A MEDLINE search (1985-2004) was performed to identify key literature. Search terms included, but were not limited to, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, children, and adolescents. The search was limited to English-language literature and randomized controlled trials. The use of atypical antipsychotics in children and adolescents has increased significantly over the past few years. Atypical antipsychotics are associated with a more favorable side-effect profile, and growing evidence supports their efficacy for aggression in this population. However, the long-term effects of these agents are unknown. No head-to-head evidence exists to suggest whether pharmacological or nonpharmacological treatments are superior for managing aggression associated with childhood and adolescent psychiatric and behavioral conditions. Future research of atypical antipsychotics in children and adolescents needs to evaluate not only the efficacy but also the effectiveness. Examination of treatment mediators and moderators may help to optimize treatment regimens and improve patient outcomes. Finally, effective interventions require the development and implementation of evidence-based treatment strategies using a multidisciplinary approach.

There is evidence that BDNF influences the birth of granule cells in the dentate gyrus, which is one of the few areas of the brain that demonstrates neurogenesis throughout life. However, studies to date have not examined this issue directly. To do so, we compared the effects of BDNF, phosphate-buffered saline (PBS), or bovine serum albumin (BSA) on neurogenesis after infusion into the hippocampus of the normal adult rat, using osmotic pumps that were implanted unilaterally in the dorsal hilus. BDNF, PBS, and BSA were infused for 2 weeks. The mitotic marker bromodeoxyuridine (BrdU) was administered twice daily during the 2-week infusion period. At least 1 month after infusion ended, brains were processed immunocytochemically using antibodies to BrdU, a neuronal nuclear protein (NeuN), or calbindin D28K (CaBP), which labels mature granule cells. Stereology was used to quantify BrdU-labeled cells in the dorsal hippocampus that were double-labeled with NeuN or CaBP. There was a statistically significant increase in BrdU(+)/NeuN(+) double-labeled cells in the granule cell layer after BDNF infusion relative to controls. The values for BrdU(+)/NeuN(+) cells were similar to BrdU(+)/CaBP(+) cells, indicating that most new neurons were likely to be granule cells. In addition, BrdU(+)/NeuN(+)-labeled cells developed in the hilar region after BDNF infusion, which have previously only been identified after severe continuous seizures (status epilepticus) and associated pathological changes. Remarkably, neurogenesis was also increased contralaterally, but BDNF did not appear to spread to the opposite hemisphere. Thus, infusion of BDNF to a local area can have widespread effects on hippocampal neurogenesis. The results demonstrate that BDNF administration to the dentate gyrus leads to increased neurogenesis of granule cells. They also show that ectopic granule cells develop after BDNF infusion, which suggests that ectopic migration is not necessarily confined to pathological conditions. These results are discussed in light of the evidence that BDNF increases neuronal activity in hippocampus. Thus, the mechanisms underlying neurogenesis following BDNF infusion could be due to altered activity as well as direct effects of BDNF itself, and this is relevant to studies of other growth factors because many of them have effects on neuronal excitability that are often not considered

OBJECTIVE: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). METHOD: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 +/- 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The Aberrant Behavior Checklist-Community Version (ABC-CV) and the Clinical Global Impression scale (CGI) were used to assess outcome. RESULTS: There was significant improvement in ABC-CV Irritability Subscale Scores (baseline mean 20.5 +/- 5.9 to final mean 10.9 +/- 7.2; p < or = .001) and in the other ABC-CV Subscales. Improvement on Clinical Global Improvement Scale severity rating was also significant (baseline mean 5.2 +/- 1.0 to final mean 4.6 +/- 1.2; p < or = .001). Twenty-five percent of the subjects responded at a dose less than 10 mg and did not tolerate the 10-mg dose, and an additional 36% responded at a dose greater than or equal to 10 mg. Final dose was unrelated to weight and only weakly correlated with age. CONCLUSIONS: This open-label study found escitalopram to be useful in treating some difficulties common in PDDs. A wide variability in dose was found that could not be accounted for by weight and only partially by age. The study provides information useful for the design of double-blind, placebo-controlled studies of escitalopram in PDDs

In this paper, we summarize the data obtained in our laboratory showing the effects of glucocorticoids on human cognitive function in older adults, young adults and children. We first present data obtained in the aged human population which showed that long-term exposure to high endogenous levels of glucocorticoids is associated with both memory impairments and a 14% smaller volume of the hippocampus. We then report on studies showing that in older adults with moderate levels of glucocorticoids, memory performance can be acutely modulated by pharmacological manipulations of glucocorticoids. In young adults, we present data obtained in our laboratory showing that cognitive processing sustained by the frontal lobes is also sensitive to acute increases of glucocorticoids. We also summarize studies showing that just as in older adults, memory performance in young adults can be acutely modulated by pharmacological manipulations of glucocorticoids. We then present a study in which we showed a differential involvement of adrenergic and glucocorticoid hormones for short- and long-term memory of neutral and emotional information. In the last section of the paper, we present data obtained in a population of young children and teenagers from low and high socioeconomic status (SES), where we showed that children from low SES present significantly higher levels of basal cortisol when compared to children from high SES. We then present new data obtained in this population showing that children and teenagers from low and high SES do not process the plausibility of positive and negative attributes in the same way. Children from low SES tended to process positive and negative attributes on a more negative note than children from high SES, and this type of processing was significantly related to basal cortisol at age 10, 12 and 14. Altogether, the results of these studies show that both bottom-up (effects of glucocorticoids on cognitive function), and top-down (effects of cognitive processing on glucocorticoid secretion) effects exist in the human population

This article presents the results of a study documenting the complex mental health needs of 95 inner city youth consecutively referred for mental health care. An ecological perspective of mental health need guides the presentation of issues and stressors that occur at the level of the individual child; within the family, school, and community; and within the larger service system context. Findings related to the intersection between child mental health needs and trauma exposure are described. In addition, the level of service involvement of these children is presented. Results reveal low rates of ongoing service involvement despite multiple, complex presenting mental health issues and significant levels of trauma exposure. Implications for urban service delivery and recommendations to prepare service providers are drawn.

With the emergence of postmodern models and critiques, the concept of symptom functionality has lost favor in the family therapy field. To be reconsidered as clinically valuable it must both demonstrate pragmatic utility and meet ethical and conceptual criteria. Functional hypotheses cannot be believed too strongly, used to blame, or employed without considerations of biology. Symptom functionality is considered in its strong and weak versions. Tempered by the more ecological weak sense, strong-sense functional hypotheses are presented as one form of description that can guide a therapist's actions

An emerging theme in systems neurobiology is that even simple forms of memory depend on activity in a broad network of cortical and subcortical brain regions. One key challenge is to understand how different components of these complex networks contribute to memory. In a new study in Molecular Pain, Tang and colleagues use a novel set of approaches to characterize the role of the anterior cingulate cortex (ACC) in the formation of Pavlovian fear memories.