Faculty Bibliography

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.

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.

The structural variability of lateral ventricles is poorly understood notwithstanding that enlarged size has been identified as an unspecific marker for psychiatric illness, including schizophrenia. This paper explores the effects of heritability and genetic risk for schizophrenia reflected in ventricular size and structure. We examined ventricular size and shape in the MRI studies of monozygotic (MZ) twin pairs discordant for schizophrenia (DS), healthy MZ twin pairs, healthy dizygotic twin pairs, and healthy nonrelated subject pairs. Heritability and effect due to disease were analyzed in two tests. First, heritability was examined by ventricle similarity between pairs of co-twins. Results show that co-twin ventricle shape similarity decreases with decreasing genetic identity, an effect not seen in the volume analysis. Co-twin shape similarity of healthy MZ twins did not differ from DS MZ twins. Second, the disease effect was examined through the ventricular differences of DS subjects to a template shape representing healthy subjects. Affected DS twins showed shape differences from healthy subjects on the left and right sides. Interestingly, unaffected DS twins also showed significant shape differences from healthy subjects for both sides. Volume comparisons did not show differences between these groups. Locality of shape difference suggests that the ventricular shape of the anterior and posterior regions is under genetic influence in both healthy controls and schizophrenia patients. Affected and unaffected groups demonstrate main shape differences, compared with healthy controls, only in the posterior region. Our results suggest that genetics have a stronger influence on the shape of lateral ventricles than do the disease-related changes in schizophrenia.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a prominent role in feeding and energy homeostasis. The rodent MCH receptor (MCH1R) is highly expressed in the nucleus accumbens shell (AcSh), a region that is important in the regulation of appetitive behavior. Here we establish a role for MCH and MCH1R in mediating a hypothalamic-limbic circuit that regulates feeding and related behaviors. Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant-like effect in the forced swim test, whereas intra-AcSh injection of MCH had the opposite effect. Expression studies demonstrated that MCH1R is present in both the enkephalin- and dynorphin-positive medium spiny neurons of the AcSh. Biochemical analysis in AcSh explants showed that MCH signaling blocks dopamine-induced phosphorylation of the AMPA glutamate receptor subunit GluR1 at Ser845. Finally, food deprivation, but not other stressors, stimulated cAMP response element-binding protein-dependent pathways selectively in MCH neurons of the hypothalamus, suggesting that these neurons are responsive to a specific set of physiologically relevant conditions. This work identifies a novel hypothalamic-AcSh circuit that influences appetitive behavior and mediates the antidepressant activity of MCH1R antagonists.

Defining the circuits that are involved in production and cessation of specific behaviors is an ultimate goal of neuroscience. Short-term behavioral habituation is the response decrement observed in many behaviors that occurs during repeated presentation of non-reinforced stimuli. Within a number of invertebrate models of short-term behavioral habituation, depression of a defined synapse has been implicated as the mechanism. However, the synaptic mechanisms of short-term behavioral habituation have not been identified within mammals. We have shown previously that a presynaptic metabotropic glutamate receptor (mGluR)-dependent depression of synapses formed by olfactory bulb afferents to the piriform (olfactory) cortex significantly contributes to adaptation of cortical odor responses. Here we show that blockade of mGluRs within the olfactory cortex of awake, behaving rats diminishes habituation of a simple odor-induced behavior, strongly implicating a central mechanism for sensory gating in olfaction

BACKGROUND: Alcoholism is often comorbid with mood disorders and suicide. We recently reported an upregulation of CB(1) receptor-mediated signaling in the dorsolateral prefrontal cortex (DLPFC) of subjects with major depression who died by suicide. In the present study, we sought to determine whether the changes in depressed suicides would also be present in alcoholic suicides and whether the endocannabinoid (EC) system plays a role in suicide in alcoholism. METHODS: The density of CB(1) receptor and its mediated [(35)S]GTP gamma S signaling were measured in the DLPFC of alcoholic suicides (AS) (n = 11) and chronic alcoholics (CA) (n = 11). The levels of ECs were measured by a liquid chromatograph/mass spectrometry. RESULTS: The CB(1) receptor density was higher in AS compared with the CA group in the DLPFC. Western blot analysis confirmed a greater immunoreactivity of the CB(1) receptor in AS. The CB(1) receptor-mediated [(35)S]GTP gamma S binding indicated a greater signaling in AS. Higher levels of N-arachidonyl ethanolamide and 2-arachidonylglycerol were observed in the DLPFC of AS. CONCLUSIONS: The elevated levels of ECs, CB(1) receptors, and CB(1) receptor-mediated [(35)S]GTP gamma S binding strongly suggest a hyperactivity of endocannabinoidergic signaling in AS. EC system may be a novel therapeutic target for the treatment of suicidal behavior

BACKGROUND: Previous neuroimaging studies have demonstrated exaggerated amygdala responses to negative stimuli in posttraumatic stress disorder (PTSD). The time course of this amygdala response is largely unstudied and is relevant to questions of habituation and sensitization in PTSD exposure therapy. METHODS: We applied blood oxygen level dependent functional magnetic resonance imaging and statistical parametric mapping to study amygdala responses to trauma-related and nontrauma-related emotional words in sexual/physical abuse PTSD and normal control subjects. We examined the time course of this response by separate analysis of early and late epochs. RESULTS: PTSD versus normal control subjects have a relatively increased initial amygdala response to trauma-related negative, but not nontrauma-related negative, versus neutral stimuli. Patients also fail to show the normal patterns of sensitization and habituation to different categories of negative stimuli. These findings correlate with measured PTSD symptom severity. CONCLUSIONS: Our results demonstrate differential time courses and specificity of amygdala response to emotional and control stimuli in PTSD and normal control subjects. This has implications for pathophysiologic models of PTSD and treatment response. The results also extend previous neuroimaging studies demonstrating relatively increased amygdala response in PTSD and expand these results to a largely female patient population probed with emotionally valenced words

Given the morbidity and difficulty of treating psychotic disorders, including schizophrenia, there has been a move toward identifying and treating adolescents and young adults who appear to be clinically at risk or 'prodromal' to psychosis. The field now has greater specificity in identification, with rates of 40-50% conversion to frank psychosis within 1-2 years. There is further evidence that medications and other treatments may have some efficacy for 'prodromal' patients, though with variable side effects. However, controversy remains about some of the inherent risks in prodromal research, such as medication exposure and stigma among false-positives. In this paper, we add to this discussion through an analysis of ethics in prodromal research from the more established field of predictive genetic testing. Issues are raised about the effects of information on patients, families, and institutions, as well as future insurability, the limits of confidentiality (as it relies on discretion of patients and families), the autonomy of minors with psychiatric symptoms, and even the risks for the true-positive patient

Fear-potentiated startle (FPS) is an increasingly popular psychophysiological method for the objective assessment of fear and anxiety. Studies applying this method often elicit the startle reflex with loud white-noise stimuli. Such intense stimuli may, however, alter psychological processes of interest by creating unintended emotional or attentional artifacts. Additionally, loud acoustic probes may be unsuitable for use with infants, children, the elderly, and those with hearing damage. Past studies have noted robust and reliable startle reflexes elicited by low intensity airpuffs. The current study compares the aversiveness of white-noise (102 dB) and airpuff (3 psi) probes and examines the sensitivity of each probe for the assessment of fear-potentiated startle. Results point to less physiological arousal and self-reported reactivity to airpuff versus white-noise probes. Additionally, both probes elicited equal startle magnitudes, response probabilities, and levels of fear-potentiated startle. Such results support the use of low intensity airpuffs as efficacious and relatively non-aversive startle probes.