Faculty Bibliography

Posttraumatic stress disorder (PTSD) is frequently underdiagnosed in maltreated samples. Protective services information is critical for obtaining complete trauma histories and determining whether to survey PTSD symptoms in maltreated children. In the current study, without protective services information to supplement parent and child report, diagnosing PTSD was missed in a significant proportion of the cases. Collaboration between mental health professionals and protective service workers is critical in determining psychiatric diagnoses and treatment needs of children involved with the child welfare system

Anxiety disorders are among the most common disorders affecting children and adolescents. Most pediatric anxiety treatment trials have been conducted in specialized research clinics and have targeted mixed samples of anxious children. In addition, the majority have focused on children ages 7 through 14 years, and used waiting-list controls which provide limited documentation of the specific contribution of CBT. Another issue is that despite the efficacy demonstrated for existing cognitive-behavioral treatments, the majority of affected children in the community do not receive mental health services. Future research is needed examining the effectiveness of interventions: (a) compared to other treatments, (b) tailored to specific disorders, and (c) for younger children below age 9 as well as adolescents. An additional critical direction will be to evaluate the efficacy of interventions in less controlled and innovative settings, and to adapt our existing treatments to be feasible for delivery by less specialized clinicians and more applicable to children with anxiety disorders who present in community settings. This special series in Cognitive and Behavioral Practice aims to expand the research agenda on interventions for pediatric anxiety disorders to address these unmet needs of anxious children and adolescents.

In the water maze, mice are trained to navigate to an escape platform located below the water's surface, and spatial learning is most commonly evaluated in a probe test in which the platform is removed from the pool. While contemporary tracking software provides precise positional information of mice for the duration of the probe test, existing performance measures (e.g., percent quadrant time, platform crossings) fail to exploit fully the richness of this positional data. Using the concept of entropy (H), here we develop a new measure that considers both how focused the search is and the degree to which searching is centered on the former platform location. To evaluate how H performs compared to existing measures of water maze performance we compiled five separate databases, containing more than 1600 mouse probe tests. Random selection of individual trials from respective databases then allowed us to simulate experiments with varying sample and effect sizes. Using this Monte Carlo-based method, we found that H outperformed existing measures in its ability to detect group differences over a range of sample or effect sizes. Additionally, we validated the new measure using three models of experimentally induced hippocampal dysfunction: (1) complete hippocampal lesions, (2) genetic deletion of alphaCaMKII, a gene implicated in hippocampal behavioral and synaptic plasticity, and (3) a mouse model of Alzheimer's disease. Together, these data indicate that H offers greater sensitivity than existing measures, most likely because it exploits the richness of the precise positional information of the mouse throughout the probe test.

Fear arousal, initiated by an environmental threat, leads to activation of the stress response, a state of alarm that promotes an array of autonomic and endocrine changes designed to aid self-preservation. The stress response includes the release of glucocorticoids from the adrenal cortex and catecholamines from the adrenal medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to the brain and influence neural structures that control emotion and cognition. To illustrate this influence, we focus on how it impacts fear conditioning, a behavioral paradigm widely used to study the neural mechanisms underlying the acquisition, expression, consolidation, reconsolidation, and extinction of emotional memories. We also discuss how stress and the endocrine mediators of the stress response influence the morphological and electrophysiological properties of neurons in brain areas that are crucial for fear-conditioning processes, including the amygdala, hippocampus, and prefrontal cortex. The information in this review illuminates the behavioral and cellular events that underlie the feedforward and feedback networks that mediate states of fear and stress and their interaction in the brain

A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within both default-mode and executive networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because of the known association between the BDNF gene and neuropsychiatric disorder, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. In addition, we demonstrate that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

Early life trauma alters later life emotions, including fear. To better understand mediating mechanisms, we subjected pups to either predictable or unpredictable trauma, in the form of paired or unpaired odor-0.5 mA shock conditioning which, during a sensitive period, produces an odor preference and no learning respectively. Fear conditioning and its neural correlates were then assessed after the sensitive period at postnatal day (PN)13 or in adulthood, ages when amygdala-dependent fear occurs. Our results revealed that paired odor-shock conditioning starting during the sensitive period (PN8-12) blocked fear conditioning in older infants (PN13) and pups continued to express olfactory bulb-dependent odor preference learning. This PN13 fear learning inhibition was also associated with suppression of shock-induced corticosterone, although the age appropriate amygdala-dependent fear learning was reinstated with systemic corticosterone (3 mg/kg) during conditioning. On the other hand, sensitive period odor-shock conditioning did not prevent adult fear conditioning, although freezing, amygdala and hippocampal 2-DG uptake and corticosterone levels were attenuated compared to adult conditioning without infant conditioning. Normal levels of freezing, amygdala and hippocampal 2-DG uptake were induced with systemic corticosterone (5 mg/kg) during adult conditioning. These results suggest that the contingency of early life trauma mediates at least some effects of early life stress through learning and suppression of corticosterone levels. However, developmental differences between infants and adults are expressed with PN13 infants' learning consistent with the original learned preference, while adult conditioning overrides the original learned preference with attenuated amygdala-dependent fear learning

This study examines the independent impact of bullying on suicide risk. Bullying was assessed by peer nomination in a prospective study of 1,655 7th and 8th grade Korean students, and suicide by youth self-report. Odds Ratios (ORs) of bullying for suicidal risks were computed, controlling for other suicide risk factors. Victim-Perpetrators and female Victims at baseline showed increased risk for persistent suicidality (OR: 2.4-9.8). Male Incident Victims exhibited increased risk for suicidal behaviors and ideations (OR = 4.4, 3.6). Female Persistent Perpetrators exhibited increased risks for suicidal behaviors; male Incident Perpetrators had increased risk for suicidal ideations (OR = 2.7, 2.3). Baseline-only male Victim-Perpetrators showed increased risk for suicidal ideations. (OR = 6.4). Bullying independently increased suicide risks