Faculty Bibliography

BACKGROUND: Uncontrollability and unpredictability are key concepts related to re-experiencing, avoidance, and hypervigilance symptoms of posttraumatic stress disorder (PTSD). However, little is known about the differential sensitivity of PTSD individuals to unpredictable stressors, relative to either healthy individuals or individuals with other anxiety disorders. This study tested the hypothesis that elevated anxious reactivity, specifically for unpredictable aversive events, is a psychophysiological correlate of PTSD. METHODS: Sixteen patients with PTSD (34.5 +/- 12.4 years) were compared with 18 patients with generalized anxiety disorder (GAD) (34.0 +/- 10.5 years) and 34 healthy control subjects (30.2 +/- 8.5 years). Participants were exposed to three conditions: one in which predictable aversive stimuli were signaled by a cue, a second in which aversive stimuli were administered unpredictably, and a third in which no aversive stimuli were anticipated. Startle magnitude was used to assess anxious responses to the threat cue and to contexts associated with each condition. RESULTS: Posttraumatic stress disorder and GAD patients showed normative enhancement of fear to the predictable threat cue, but the PTSD group displayed elevated anxiety during the unpredictable condition compared with participants with GAD and healthy control subjects. CONCLUSIONS: Anxious reactivity to unpredictable aversive events was heightened in PTSD but not in GAD and healthy subjects. Prior works also found signs of increased reactivity to unpredictable threat in panic disorder (PD), suggesting that PTSD and PD may involve shared vulnerability. As such, the current results inform understandings of classification, pathophysiology, and psychopharmacology of anxiety disorders, generally, and PTSD and panic disorder specifically.

BACKGROUND: Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK(1)) receptors in brain using the nonpeptide antagonist radioligand, [(18)F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK(1) receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a drug-induced panic attack releases substance P in brain, as measured by decreased binding of [(18)F]SPA-RQ. METHODS: Positron emission tomography scans with [(18)F]SPA-RQ were performed in 14 patients with panic disorder and 14 healthy subjects. Of these two groups, 7 patients and 10 healthy subjects were scanned twice, once at baseline and once after injection of doxapram, a drug that induces panic attacks. RESULTS: NK(1) receptor binding in patients (n = 14) compared with that in healthy subjects (n = 14) was significantly decreased by 12% to 21% in all brain regions. Doxapram effectively produced panic attacks in 6 of 7 patients with panic disorder but only 2 of 10 healthy subjects. Doxapram caused no significant change of [(18)F]SPA-RQ binding in either patients or healthy subjects. CONCLUSIONS: Although induction of a panic attack has no significant effect on [(18)F]SPA-RQ binding to NK(1) receptors, patients with panic disorder have widespread reduction of NK(1) receptor binding in brain.

RATIONALE: Psychostimulants, such as yohimbine and amphetamine, can enhance learning and memory. Extinction of conditioned fear involves new learning, so we asked whether psychostimulants could enhance this learning. Previous work suggests that yohimbine facilitates extinction, using freezing as a fear measure. However, psychostimulant-induced alterations in locomotion can confound freezing measurements. Furthermore, the effects of amphetamine on fear extinction have never been examined. OBJECTIVE: We evaluated the effectiveness of yohimbine and amphetamine in enhancing fear extinction. In addition to freezing, we measured bar-press suppression, which is less sensitive to changes in locomotion. We asked: Do psychostimulants reduce fear during extinction training when drug is present? Does learning extinction with psychostimulants result in better extinction retention? MATERIALS AND METHODS: Rats received fear conditioning on day 1 followed by partial extinction training on days 2 and 3. Yohimbine (1.0, 2.0, or 5.0 mg/kg, i.p.), amphetamine (1.0 mg/kg, i.p.), or vehicle were injected prior to extinction on day 2. RESULTS: Yohimbine dose-dependently reduced freezing during extinction training on day 2, whereas bar-press suppression was reduced at the highest dose only. When tested drug-free, yohimbine-treated rats showed equivalent levels of freezing and suppression to controls. Amphetamine also decreased freezing during extinction, but did not decrease suppression. During the drug-free test, there was no difference between amphetamine-treated rats and controls in either measure. CONCLUSIONS: Although yohimbine and amphetamine are capable of decreasing freezing, neither drug strengthened retention of fear extinction. Based on these rodent findings, psychostimulants may not be suitable adjuncts to extinction-based therapies for the treatment of anxiety disorders.

This study used a Competency Questionnaire modified for medical surgical patients (CQ-Med). Twenty-nine patients (ages 65-94 years) admitted to a geriatric medicine unit were studied. Along with the CQ-Med, patients were administered several WAIS-R subtests, the Blessed Dementia Scale (BDS), and Mini Mental State Exam (MMSE). Additionally, a blind forensic evaluation for competency to consent to hospitalization and treatment was performed for the purpose of validation of the CQ-Med. Results of the study found that, as expected, increased age was correlated with decreasing performance on the CQ-Med and decreased findings of competence by clinical exam. However, there was great variability within each age group, demonstrating individual differences in the progress of declining competency. CQ-Med scores also correlated well with the WAIS-R subtest raw and scaled scores. Scores on the MMSE and BDS were less well correlated. The CQ-Med may be a useful adjunct in assessing declining competency in geriatric patients

OBJECTIVE: To examine whether preschool children with Attention deficit/hyperactivity disorder (ADHD) utilize more speech and language therapy (ST), occupational therapy (OT), and physical therapy (PT) services and are more likely to be placed in special education (SPED) classrooms as compared to their peers. Corresponding financial consequences were also examined. METHODS: The amount of ST, OT, and PT, as well as SPED placements, was examined in 3- and 4-year-old children with and without ADHD (n = 109 and n = 97, respectively) during the baseline portion of an ongoing, 5-year longitudinal study. Costs for individual services and aggregate cost were determined per child and compared across groups. RESULTS: Preschool children with ADHD were more likely to receive individual and multiple services. Higher rates of service utilization translated into increased costs for each individual service with the exception of PT. CONCLUSIONS: A comprehensive understanding of service utilization in the early years of development is important in addressing the increased service use in the preschool years and assist in guiding allocation of resources.

Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system and is thought to be behaviorally mediated by olfactory habituation memory. Data from our laboratory have shown that odor-specific adaptation in piriform neurons, mediated at least partially by synaptic adaptation between the olfactory bulb outputs and piriform cortex pyramidal cells, is highly odor specific, while that observed at the synaptic level is specific only to certain odor features. Behavioral data show that odor habituation memory at short time constants corresponding to synaptic adaptation is also highly odor specific and is blocked by the same pharmacological agents as synaptic adaptation. Using previously developed computational models of the olfactory system we show here how synaptic adaptation and potentiation interact to create the observed specificity of response adaptation. The model analyzes the mechanisms underlying the odor specificity of habituation, the dependence on functioning cholinergic modulation, and makes predictions about connectivity to and within the piriform neural network. Predictions made by the model for the role of cholinergic modulation are supported by behavioral results

Parent cultural adaptation and preschool behavioral and socioemotional functioning were examined in a community sample of urban families from diverse cultural backgrounds. Participants were 130 families of children (mean age = 4.1 years) attending eight public Pre-Kindergarten programs in urban communities. Parents completed a measure of cultural adaptation that taps into acculturation and enculturation, and teachers reported on children's externalizing problems, internalizing problems and adaptive behavior in the classroom. Parents' ethnic identity was a significant predictor of children's functioning. The retention of parents' culture of origin and specific aspects of acculturation are related to positive outcomes in a sample of culturally diverse families of preschoolers living in urban communities. Bicultural parents (those with high ethnic and US American identity) had children with lower levels of internalizing problems and higher levels of adaptive behavior relative to parents who were not bicultural. Implications for enhancing positive child outcomes through the promotion of parental ethnic identity are discussed

The nervous system must provide a mechanism for very precise discrimination of differing patterns of activity, yet at the same time, there must be a mechanism for generalization to prevent all experiences from being independent and novel. Pattern separation and completion by cortical circuits contribute to these processes, respectively. Based on theoretical and computational models of the piriform cortex and experimental designs developed for hippocampal spatial memory, we provide evidence for pattern separation and completion in the olfactory system and demonstrate the predictive power of these two processes for behavioral odor perception