Faculty Bibliography

It is currently believed that the acquisition of classically conditioned fear involves potentiation of conditioned thalamic inputs in the lateral amygdala (LA). In turn, LA cells would excite more neurons in the central nucleus (CE) that, via their projections to the brain stem and hypothalamus, evoke fear responses. However, LA neurons do not directly contact brain stem-projecting CE neurons. This is problematic because CE projections to the periaqueductal gray and pontine reticular formation are believed to generate conditioned freezing and fear-potentiated startle, respectively. Moreover, like LA, CE may receive direct thalamic inputs communicating information about the conditioned and unconditioned stimuli. Finally, recent evidence suggests that the CE itself may be a critical site of plasticity. This review attempts to reconcile the current model with these observations. We suggest that potentiated LA outputs disinhibit CE projection neurons via GABAergic intercalated neurons, thereby permitting associative plasticity in CE. Thus plasticity in both LA and CE would be necessary for acquisition of conditioned fear. This revised model also accounts for inhibition of conditioned fear after extinction

BACKGROUND: For many years, researchers and clinicians have described parent reports of an unusual developmental phenomenon in a substantial minority of children with Autistic Spectrum Disorders (ASD), the acquisition and then loss of communication skills during the second year of life. METHODS: As part of a longitudinal study of 110 children referred for assessments of possible autism at age 2 years or younger, 21 developmentally delayed children and 33 typically developing controls, 19 children were described by their parents at age 2 as having gained and lost spontaneous, meaningful words, and 12 children as having a history of less specific loss of imitated words or nonword vocalizations. A battery of diagnostic and cognitive tasks was administered to all children at study entrance, at ages 3 (for the referral children only) and 4 or 5 (for referral and developmentally delayed children). RESULTS: Results indicated that the acquisition of a small number of spontaneous words used meaningfully and consistently followed by loss of all words, often associated with other social changes, was unique to children diagnosed at 5 years with ASD. Few differences, besides those that defined the pattern of word loss, emerged between children with ASD with and without word loss. Loss of less specific, nonword vocalizations was associated with cognitive delay, with or without autism. CONCLUSIONS: Word loss is a reliably identifiable phenomenon in early childhood that appears to be unique, but not universal to, ASD. Histories and outcome of children with word loss were not in keeping with a sudden change from normal to abnormal functioning, but did suggest that this type of loss in the second year of life may be a useful 'red flag' for ASD in a significant minority of cases

Children who experience homelessness are at increased risk for a range of health and mental health problems. In spite of this increased risk, they are often less likely to receive appropriate services. School-based programs offer considerable potential to reduce the gap between needs and appropriate services for these youth; however, there are few examples of such programs in the published literature. This article provides information from a mental and physical health prevention program and needs assessment for at-risk children, who were experiencing homelessness or were from very low-income families, which was piloted during a summer camp program in an urban school. Results of the needs assessment indicated that children residing in homeless shelters reported less consistent access to medical and dental care than children residing with their families. It is interesting that children experiencing homelessness were more likely to report that they had participated in counseling than did children from low-income families. Satisfaction ratings of prevention activities conducted in the program were positive for students and teachers.

Childhood is a time filled with wondrous changes, as brain plasticity permits experiences to shape the immature brain to meet the demands of the environment. Change occurs at various levels--from neuroanatomy, including within a given region and its connectivity to other regions, to the function of neurotransmitter systems and their reactivity to pharmacological agents in the short- and long-term. The nature and degree to which drug exposure influences the final adult topography is influenced greatly by the maturational phase of these critical factors. Moreover, evidence is slowly emerging that suggests that the long-term effects of drug exposure are delayed and expressed once the vulnerable system reaches maturation (i.e., typically during adulthood). This phenomenon is known as neuronal imprinting and occurs when the effects of drug exposure outlast the drug itself. Thus, understanding the persistent effects critically depends on the window of observation. Embracing this concept should influence how we conduct preclinical assessments of developmental drug exposure, and ultimately how we conduct clinical assessments of drug efficacy, effectiveness, and safety for the treatment of childhood psychiatric disorders. In this article, we present a model to provide a heuristic framework for making predictions about imprinted effects of childhood drug exposure. We then review epidemiological data on attention deficit hyperactivity disorder (ADHD) and childhood depression, prescription practices, and what is known regarding the long-term consequences of drug exposure in these populations. We conclude with a discussion of the current status of preclinical studies on juvenile stimulant exposure

Systemic effects of anesthesia on the dynamics of the apnea-induced Blood Oxygen Level Dependent (BOLD) signal is still not clear. In the present study, the dynamics of the fMRI-BOLD signal and blood flow using laser Doppler flowmetry (LDF) was studied in rats in response to apnea. Two anesthetics namely pentobarbital and urethane, hypothesized to have distinct effects on the mean arterial blood pressure (MAP) were used. During normoxic baseline conditions, MAP decreased in response to apnea in rats anesthetized with pentobarbital but increased with urethane. However, MAP did not change significantly in response to apnea during hyperoxic or hypercapnic baseline conditions with both anesthetics. LDF increased in response to apnea during normoxia, hyperoxia or hypercapnia and was influenced by MAP during normoxia. Apnea-induced BOLD signal dynamics was similar with both anesthetics, dominated by an alteration in arterial blood oxygenation and independent of changes in MAP. Our results suggest that anesthesia-dependent MAP change modulates the apnea-induced cerebral blood flow (CBF) response but has a minimal effect on the fMRI-BOLD signal probably due to uncoupling of CBF and oxygen consumption

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of a variety of fear or anxiety disorders. Although they inhibit the reuptake of serotonin within hours of administration, therapeutic improvement only occurs after several weeks. In this study, we used fear conditioning to begin to understand how acute and chronic SSRI treatment might differentially affect well-characterized fear circuits. METHODS: We evaluated the effects of acute and chronic treatment with the SSRI citalopram on the acquisition of auditory fear conditioning. To further understand the role of serotonin in modulating fear circuits, we compared these effects with those of acute and chronic administration of the antidepressant tianeptine, a purported serotonin reuptake enhancer. RESULTS: We found that acute administration of the SSRI citalopram enhanced acquisition, whereas chronic treatment reduced the acquisition of auditory fear conditioning. In comparison, treatment with tianeptine had no effect acutely but also reduced the acquisition of tone conditioning when administered chronically. CONCLUSIONS: Our findings with citalopram are consistent with the clinical effects of SSRI treatment seen in patients with anxiety disorders, in which anxiety is often increased during early stages of treatment and decreased after several weeks of treatment. The findings also indicate that auditory fear conditioning can be a useful tool in understanding differences in the effects of short-term and long-term antidepressant treatment with serotonergic medications

BACKGROUND: Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences. METHODS: We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared. RESULTS: Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males. CONCLUSIONS: These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.

BACKGROUND: Context conditioning has been suggested to model clinical anxiety, but context, as manipulated in animal models, has not been translated to human studies. A virtual environment might prove to be the ideal tool for innovative experimental paradigms to study explicitly cued fear and contextual anxiety in humans. METHODS: Subjects were guided through a virtual environment that consisted of two rooms connected by a street scene. In each of the rooms, a blue and a yellow panel on a wall served as explicit conditioned stimuli (CS). The panels were displayed several times. One of the panels (CS+) was associated with a shock in one of the rooms (shock room). No shock was administered in the other room (safe room). Acoustic startle stimuli were administered in the presence and in the absence of the panels to assess explicit cued conditioning to the CS and context conditioning to the rooms, respectively. RESULTS: Startle was potentiated by the CS+ in both rooms, which suggests generalization of fear across contexts. After acquisition, startle was potentiated in the shock room, compared with the safe room, in the absence of the CS+. CONCLUSIONS: These results support the future use of virtual reality to design new conditioning experiments to study both fear and anxiety.

The purpose of this study was to determine whether asthma status and severity have an impact on the quality of life of urban elementary school children. Participants were 1292 caregiver-child dyads from six schools serving low-income, ethnic minority, urban families; 53% of the children were female. Caregivers provided data on the children's asthma diagnosis and frequency in the last 12 months of asthma symptoms, use of medication for asthma, emergency room visits, and hospitalizations. Using the KINDL, a generic quality of life instrument, children reported on their health-related quality of life (HRQL). Results revealed a high prevalence of current asthma (18%). No differences were found in HRQL based on having current asthma or the severity of asthma as assessed by proxy measures of health care utilization and limited functioning. These findings are consistent with previous research indicating that HRQL is influenced by several factors other than asthma status and severity. The implications of these results for intervention are discussed