Faculty Bibliography

In addition to its potent effects on vasculature, it has become clear that vascular endothelial growth factor (VEGF) has effects on both neurons and glia, and recent studies suggest that it can be neuroprotective. To determine potential mechanisms underlying this neuroprotection, recombinant human VEGF was bath applied to adult rat hippocampal slices, and both extracellular and intracellular recordings were used to examine intrinsic properties and synaptic responses of hippocampal principal neurons. Initial studies in area CA1 showed that VEGF significantly reduced the amplitude of responses elicited by Schaffer collateral stimulation, without influencing membrane properties. Similar effects occurred in CA3 pyramidal cells and dentate gyrus granule cells when their major glutamatergic afferents were stimulated. Because VEGF expression is increased after seizures, effects of VEGF were also examined in rats with recurrent spontaneous seizures. VEGF reduced spontaneous discharges in slices from these rats but had surprisingly little effect on epileptiform discharges produced by disinhibition of slices from control rats. These results demonstrate a previously unknown effect of VEGF on neuronal activity and also demonstrate a remarkable potency in the epileptic brain. Based on this, we suggest that VEGF or VEGF-related targets could provide useful endpoints to direct novel therapeutic strategies for epilepsy

The purpose of the study was to better understand past findings of nasal chemosensory hypersensitivity in pregnant women by recording chemosensory event-related potentials (CSERPs) for information about cortical neuronal allocation (amplitudes) and temporal processing (latencies) of three concentrations of pyridine ranging from predominantly olfactory to trigeminal in activation in 15 pregnant and 15 non-pregnant women. CSERP components of primarily sensory (N1 and P2) and cognitive (P3) origin were evaluated. The results displayed no group differences in either N1 or P2 amplitudes or latencies, but tendencies of larger amplitudes and shorter latencies for P3 in pregnant women. This implies that pregnant women's hypersensitivity may more likely be referred to cognitive than sensory processing.

BACKGROUND:Most patients with obsessive-compulsive disorder (OCD) show only partial reduction of symptoms with standard therapy. Recent imaging data suggests glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent, in treatment-resistant OCD. METHODS:Thirteen patients aged between 18 and 65 years with a primary diagnosis of OCD that had proven resistant to standard treatment were treated with the addition of riluzole to their existing pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were obtained weekly. RESULTS:Thirteen treatment-resistant OCD patients received riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13 patients, 7 (54%) demonstrated a >35% reduction in Y-BOCS scores, and 5 (39%) were categorized as treatment responders. HAM-D and HAM-A scores for the group also significantly improved over time. Riluzole was well tolerated with no serious adverse effects noted. CONCLUSIONS:Riluzole appears to have significant antiobsessional, antidepressant, and antianxiety properties. The addition of this agent may be of practical clinical benefit in patients with OCD.

Neuropeptides vasopressin and oxytocin regulate a variety of behaviors ranging from maternal and pair bonding to aggression and fear. Their role in modulating fear responses has been widely recognized, but not yet well understood. Animal and human studies indicate the major role of the amygdala in controlling fear and anxiety. The amygdala is involved in detecting threat stimuli and linking them to defensive behaviors. This is accomplished by projections connecting the central nucleus of the amygdala (CeA) to the brain stem and to hypothalamic structures, which organize fear responses. A recent study by Huber et al demonstrates that vasopressin and oxytocin modulate the excitatory inputs into the CeA in opposite manners. Therefore this finding elucidates the mechanisms through which these neuropeptides may control the expression of fear

This paper presents the clinical/developmental framework underlying a new diagnostic observational tool, the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). The special importance of observation for clinical assessment during the preschool period is delineated. The developmental rationale for a multi-dimensional assessment of disruptive behavior in young children, including problems in modulation of negative affect and low competence is discussed. The ways in which the DB-DOS will elucidate distinctions between normative and atypical behavior during this developmental period via (a) the integration of qualitative and quantitative dimensions of behavior within a clinically-sensitive coding system, (b) the observation of child behavior both within, and outside of, the parent-child context and (c) the use of specially designed tasks to 'press' for clinically salient behaviors are addressed. The promise of this new method for yielding a more precise, developmentally based description of the phenotype of early onset disruptive behavior problems and for providing a standardized clinical tool for observational assessment of disruptive behavior in young children is presented. Large-scale validation of the measure is currently underway

The last two decades have seen a dramatic change in the treatment approaches used to address adolescent depression. Research studies on the characteristics of adolescents with depression have pinpointed problems in thinking, behavior, and social interactions that are linked to the disorder and its symptoms. Clinical researchers have used this information to develop specific treatments for depression that have been put to the empirical test with good results. This article reviews the rationale, treatment content, and effectiveness of four structured and targeted treatments for depression in youth as they have been applied to adolescents. The approaches include cognitive-behavioral therapy, primary and secondary control enhancement therapy, interpersonal psychotherapy for adolescents, and systemic-behavioral family therapy. Each of these methods contributes to improvements in rates of depression and depressive symptoms for adolescents with all forms of depression, including major depressive disorder. Thus, they provide advances in the care of the depressed adolescent. Their status in relation to the use of medication and their limits are discussed. Provided is a set of guidelines for primary practitioners to facilitate teenage engagement in therapy and make selections for referrals sources. (journal abstract)

OBJECTIVE: Little is known about neuropsychological and social-cognitive function in patients with pediatric bipolar disorder. Identification of specific deficits and strengths that characterize pediatric bipolar disorder would facilitate advances in diagnosis, treatment, and research on pathophysiology. The purpose of this study was to test the hypothesis that youths with bipolar disorder would perform more poorly than matched healthy comparison subjects on measures of social cognition, motor inhibition, and response flexibility. METHOD: Forty outpatients with pediatric bipolar disorder and 22 comparison subjects (no differences in age, gender, and IQ) completed measures of social cognition (the pragmatic judgment subtest of the Comprehensive Assessment of Spoken Language, facial expression recognition subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale, the oral expression subtest of the Test of Language Competence), inhibition and response flexibility (stop and stop-change tasks), and motor inhibition (continuous performance tasks). RESULTS: Pediatric bipolar disorder patients performed more poorly than comparison subjects on social-cognitive measures (pragmatic judgment of language, facial expression recognition) and on a task requiring response flexibility. These deficits were present in euthymic patients. Differences between patients and comparison subjects could not be attributed to comorbid attention deficit hyperactivity disorder. CONCLUSIONS: Findings of impaired social cognition and response flexibility in youths with pediatric bipolar disorder suggest continuity between pediatric bipolar disorder and adult bipolar disorder. These findings provide a foundation for neurocognitive research designed to identify the neural mechanisms underlying these deficits.

OBJECTIVE: Maternal filicide, or child murder by mothers, occurs more frequently in the United States than in other developed nations. However, little is known about factors that confer risk to children. The authors review the literature to identify predictors of maternal filicide and identify gaps in knowledge about maternal filicide. METHOD: Databases were systematically searched for studies of maternal filicide and neonaticide (murder in the first day of life) that were conducted in industrialized countries and were published in peer-reviewed, English-language publications after 1980. RESULTS: Women who committed filicide varied greatly by the type of sample studied. Neonaticide was often committed by young, poor, unmarried women with little or no prenatal care. CONCLUSIONS: The results of the review suggest that little is known about the predictors of maternal filicide and that a systematic, focused program of research on reliable markers for maternal filicide is needed to better prevent these events.