Faculty Bibliography

Survival in a dangerous environment requires learning about stimuli that predict harm. Although recent work has focused on the amygdala as the locus of aversive memory formation, the hypothalamus has long been implicated in emotional regulation, and the hypothalamic neuropeptide orexin (hypocretin) is involved in anxiety states and arousal. Nevertheless, little is known about the role of orexin in aversive memory formation. Using a combination of behavioral pharmacology, slice physiology, and optogenetic techniques, we show that orexin acts upstream of the amygdala via the noradrenergic locus coeruleus to enable threat (fear) learning, specifically during the aversive event. Our results are consistent with clinical studies linking orexin levels to aversive learning and anxiety in humans and dysregulation of the orexin system may contribute to the etiology of fear and anxiety disorders.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and cannabis use are each associated with specific cognitive deficits. Few studies have investigated the neurocognitive profile of individuals with both an ADHD history and regular cannabis use. The greatest cognitive impairment is expected among ADHD Cannabis Users compared to those with ADHD-only, Cannabis use-only, or neither. METHODS: Young adults (24.2+/-1.2 years) with a childhood ADHD diagnosis who did (n=42) and did not (n=45) report past year>/=monthly cannabis use were compared on neuropsychological measures to a local normative comparison group (LNCG) who did (n=20) and did not (n=21) report past year regular cannabis use. Age, gender, IQ, socioeconomic status, and past year alcohol and smoking were statistical covariates. RESULTS: The ADHD group performed worse than LNCG on verbal memory, processing speed, cognitive interference, decision-making, working memory, and response inhibition. No significant effects for cannabis use emerged. Interactions between ADHD and cannabis were non-significant. Exploratory analyses revealed that individuals who began using cannabis regularly before age 16 (n=27) may have poorer executive functioning (i.e., decision-making, working memory, and response inhibition), than users who began later (n=32); replication is warranted with a larger sample. CONCLUSIONS: A childhood diagnosis of ADHD, but not cannabis use in adulthood, was associated with executive dysfunction. Earlier initiation of cannabis use may be linked to poor cognitive outcomes and a significantly greater proportion of the ADHD group began using cannabis before age 16. Regular cannabis use starting after age 16 may not be sufficient to aggravate longstanding cognitive deficits characteristic of ADHD.

The rates of comorbid anxiety as well as the presentation of challenging behaviors are elevated within the autism spectrum disorder (ASD) population. The current study utilizes the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) to explore the relationship of anxiety/repetitive behavior symptom severity and challenging behaviors in infants and toddlers with ASD. Children with ASD who evinced more severe impairment associated with anxiety/repetitive behavior (n = 94) demonstrated higher rates of overall challenging behaviors than those with ASD who evinced no to minimal anxiety impairment (n = 291). Specifically, a comparison of individual challenging behavior items indicated that the infants and toddlers with moderate to severe anxiety impairment exhibited more significant challenging behaviors under the domains of aggression/destruction, stereotypies, and self-injurious behavior than children with no to minimal impairment. This study adds to the literature evidencing an exacerbation of challenging behaviors by comorbid psychopathology in individuals with ASD. Clinical implications of these results are discussed. (C) 2013 Elsevier Ltd. All rights reserved.

We examined whether error monitoring, operationalized as the degree to which individuals slow down after committing an error (i.e., posterror slowing), is differentially important in the learning of rule-based versus information-integration category structures. Rule-based categories are most efficiently solved through the application of an explicit verbal strategy (e.g., "sort by color"). In contrast, information-integration categories are believed to be learned in a trial-by-trial, associative manner. Our results indicated that posterror slowing predicts enhanced rule-based but not information-integration category learning. Implications for multiple category-learning systems are discussed.

Background: Children learn to attach to the caregiver, even when experiencing abuse. We explore unique attributes of the learning attachment system in infant rodents to better understand how the brain supports this learning. Our previous work showed that the amygdala's learning plasticity is suppressed during attachment learning with an abusive caregiver. Here we present data indicating that, although the amygdala is not supporting fear learning, it is responding to the trauma and organizing to produce laterlife pathology associated with malfunctioning amygdala. Methods: Infant rats pups were either reared with a maltreating mother for natural attachment learning or classically conditioned in an experimentally controlled attachment learning paradigm that included pain (odor- 0.5mA shock) or no pain (odor-tactile stimulation). These procedures produce a maternal odor that pups require to interact with the mother. Controls included rearing with a typical mother and controls that do not learn the maternal odor (presentations of rewards unpaired with the odor). Social behaviors and neural activity (microarray, microdialysis, electrophysiology, 2-DG autoradiography) were assessed in pups and older animals to explore short-term and enduring effects. Results: The short-term effects of pups experiencing pain within attachment (abusive mother, learning the maternal odor with pain) seem minimal since pups showed attachment to the caregiver and the amygdala did not participate in behaviourFsimilarly to that expressed by controls. While this attachment system ensures infants attach to their caregiver regardless of the quality of care received, the longterm effects indicate these early-life experiences with maltreatment have costs. Amygdala and behavioural abnormalities emerge around weaning and continue into adulthood. However, presentation of the early life maternal odor (natural and learned) appears to normalize both the behaviour and amygdala. Conclusions: Together, these data suggest that the attachmen!

This two-part study describes the development and validation of a method for quantifying adolescent personality pathology using the latest edition of the Shedler-Westen Assessment Procedure for Adolescents (SWAP-II-A), an instrument designed to be used by clinically experienced observers. In Study 1, experienced psychologists and psychiatrists described a normative clinical sample of 950 North American patients. Study 2 applied the SWAP-II-A in a day treatment setting. Results indicated that SWAP-II-A personality disorder (PD) scales evidenced high internal consistency, construct validity with Diagnostic and Statistical Manual of Mental Disorders (5th ed.) symptoms and diagnoses, and concurrent validity with Child Behavior Checklist (CBCL) ratings. Independent observers saw patients similarly, and PD assessments were significantly associated with CBCL scale scores and ward behavior. C1 [DeFife, Jared A.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Malone, Johanna C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [DiLallo, John] NYU, Sch Med, New York City Adm Childrens Serv, New York, NY 10003 USA. [Westen, Drew] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Westen, Drew] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA