Faculty Bibliography

In this pilot study, amygdala connectivity related to trauma symptoms was explored using resting-state functional magnetic resonance imaging (R-fMRI) in 23 healthy adolescents ages 13-17 years with no psychiatric diagnoses. Adolescents completed a self-report trauma symptom checklist and a R-fMRI scan. We examined the relationship of trauma symptoms to resting-state functional connectivity of the amygdala. Increasing self-report of trauma symptoms by adolescents was associated with increasing functional connectivity with the right amygdala and a local limbic cluster and decreasing functional connectivity with the amygdala and a long-range frontoparietal cluster to the left amygdala, which can be a hallmark of immaturity. These pilot findings in adolescents provide preliminary evidence that even mild trauma symptoms can be linked to the configuration of brain networks associated with the amygdala.

OBJECTIVE: The aim of the current study is to investigate challenging behavior in children who may no longer meet criteria for an autism spectrum disorder (ASD) diagnosis according to the proposed fifth edition of the Diagnostic and Statistical Manual (DSM-5). METHOD: Children and adolescents (n = 459) were separated into three groups including those who met criteria for ASD according to the DSM-5 criteria (n = 219); those who will no longer qualify for an ASD diagnosis according to the DSM-5 but met criteria according to the DSM-IV-TR (n = 109); and a control group (n = 131). Scores on the Autism Spectrum Disorders - Problem Behaviors for Children (ASD-PB-C) were compared among groups. RESULTS: The DSM-5 captured a slightly more impaired population in terms of problem behavior. CONCLUSION: Implications regarding access to treatment for those no longer meeting criteria need to be taken into consideration in the coming months.

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

OBJECTIVE: We sought to establish prevalence rates and detail patterns of comorbidity for generalized anxiety disorder, separation anxiety disorder, and social phobia in preschool-aged children. METHOD: The Duke Preschool Anxiety Study, a screen-stratified, cross-sectional study, drew from pediatric primary care and oversampled for children at risk for anxiety. A total of 917 parents of preschool children (aged 2-5 years) completed the Preschool Age Psychiatric Assessment. RESULTS: Generalized anxiety disorder, separation anxiety disorder, and social phobia are common in preschool-aged children attending pediatric primary care. Three-fourths of preschoolers with an anxiety disorder only had a single anxiety disorder. Generalized anxiety disorder displayed the greatest degree of comorbidity: with separation anxiety disorder (odds ratio [OR] = 4.1, 95% CI = 2.0-8.5), social phobia (OR = 6.4, 95% CI = 3.1-13.4), disruptive behavior disorders (OR = 5.1, 95% CI = 1.6-15.8), and depression (OR = 3.7, 95% CI = 1.1-12.4). CONCLUSIONS: The weakness of association between generalized anxiety disorder and depression stands in contrast to substantial associations between these 2 disorders reported in older individuals. Attenuated associations in preschool-aged children could translate into clinical opportunities for targeted early interventions, aimed at modifying the developmental trajectory of anxiety disorders.

BACKGROUND: Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. METHODS: Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323). RESULTS: The mean (SD) paternal age was 29.2 (6.2) years, range (16-50) and maternal age was 26.8 (5.7) years, range (17-42) at childbirth for the 201 adolescents (ages 12-17years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p<0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages. CONCLUSIONS: APA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder.

Over the past decade there has been increasing interest in the idea that marriage and perhaps other forms of interpersonal support can buffer the negative effects of poverty. The current study tests the hypothesis that marital status, perceived social support and neighborhood collective efficacy can moderate the effects of economic adversity on depressive symptoms among parents. Hierarchical Linear Modeling was used to analyze data from the Project on Human Development in Chicago Neighborhoods. Participants were 1,957 mothers of minor children. Analysis of main effects revealed associations between neighborhood SES (beta = -0.69, SE (0.15), p < .001), family income (beta = -0.11, SE (0.05), p = .02) financial strain (beta = 0.51, SE (0.18), p = .004), being single (beta = 0.63, SE (0.24), p = .009) and perceived social support (beta = -0.22, SE (0.03), p < .001) on depressive symptoms. The hypothesis that interpersonal resources can buffer the effects of economic adversity was not supported. There were no significant interactions between marital status and economic adversity. There was a significant interaction between perceived social support and neighborhood level socioeconomic status (beta = -0.07, SE (0.03), p = .04) but the effects of social support were weakest in neighborhoods characterized by low socioeconomic status.

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.

Effective navigation of the social world relies on the correct interpretation of facial emotions. This may be particularly important in formative years. Critically, literature examining the emergence of face processing in youth (children and adolescents) has focused on the neural and behavioral correlates of processing adult faces, which are relationally different from youth participants, and whose facial expressions may convey different meaning than faces of their peers. During a functional magnetic resonance imaging (fMRI) scan, we compared concurrent neural and behavioral responses as youth (N=25) viewed validated, emotionally varied (i.e., anger, fear, happy, and neutral) adult and child face stimuli. We observed that participants made fewer errors when matching adult, compared to child, face stimuli, and that while similar brain regions were involved in processing both adult and child faces, activation in the face processing neural network was greater for adult than child faces. This was true across emotions, and also when comparing neutral adult versus neutral child faces. Additionally, a valence by stimuli-type effect was observed within the amygdala. That is, within adult face stimuli, negative and neutral face stimuli elicited the largest effects, whereas within child face stimuli, happy face stimuli elicited the largest amygdala effects. Thus, heightened engagement of the amygdala was observed for happy child and angry adult faces, which may reflect age-specific salience of select emotions in early life. This study provides evidence that the relational age of the perceived face influences neural processing in youth.

Aquaporin-4 (AQP4) is the major water channel expressed in the central nervous system (CNS) and is primarily expressed in glial cells. Many studies have shown that AQP4 regulates the response of the CNS to insults or injury, but far less is known about the potential for AQP4 to influence synaptic plasticity or behavior. Recent studies have examined long-term potentiation (LTP), long-term depression (LTD), and behavior in AQP4 knockout (KO) and wild-type mice to gain more insight into its potential role. The results showed a selective effect of AQP4 deletion on LTP of the Schaffer collateral pathway in hippocampus using an LTP induction protocol that simulates pyramidal cell firing during theta oscillations (theta-burst stimulation; TBS). However, LTP produced by a different induction protocol was unaffected. There was also a defect in LTD after low frequency stimulation (LFS) in AQP4 KO mice. Interestingly, some slices from AQP4 KO mice exhibited LTD after TBS instead of LTP, or LTP following LFS instead of LTD. These data suggest that AQP4 and astrocytes influence the polarity of long-term synaptic plasticity (potentiation or depression). These potentially powerful roles expand the influence of AQP4 and astrocytes beyond the original suggestions related to regulation of extracellular potassium and water balance. Remarkably, AQP4 KO mice did not show deficits in basal transmission, suggesting specificity for long-term synaptic plasticity. The mechanism appears to be related to neurotrophins and specifically brain-derived neurotrophic factor (BDNF) because pharmacological blockade of neurotrophin trk receptors or scavenging ligands such as BDNF restored plasticity. The in vitro studies predicted effects in vivo of AQP4 deletion because AQP4 KO mice performed worse using a task that requires memory for the location of objects (object placement). However, performance on other hippocampal-dependent tasks was spared. The results suggest an unanticipated and selective role of AQP4 in synaptic plasticity and spatial memory, and underscore the growing appreciation of the role of glial cells in functions typically attributed to neurons. Implications for epilepsy are discussed because of the previous evidence that AQP4 influences seizures, and the role of synaptic plasticity in epileptogenesis.