Faculty Bibliography

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 +/- 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.

OBJECTIVE: Most youths experiencing a psychiatric crisis present to emergency departments (EDs) that lack the specialized staff to evaluate them, so youths are often discharged without appropriate mental health assessment or treatment. To better understand the needs of this population, this study described clinical details and disposition associated with visits for psychiatric emergencies to a specialized ED staffed 24/7 by child psychiatrists. METHODS: Through retrospective chart review, 1,180 visits to the ED during its first year of operation were reviewed for clinical characteristics, prior service utilization, and demographic characteristics. Bivariate analyses (chi-square test and Wilcoxon rank sum test) compared differences in disposition (evaluate and release, brief stabilization, and inpatient psychiatric admission) associated with characteristics of the children's first visit (N=885). Measures with bivariate association of p<.10 were further assessed by using multinomial logistic regression analyses. RESULTS: For most visits (59%), children were evaluated and released, 13% were briefly stabilized, and 28% were admitted for psychiatric treatment. Youths with mood or psychotic disorders were more likely to be admitted, as were those with current suicidality or aggression. Many youths who presented with aggression were also identified as having suicidality or self-harm. CONCLUSIONS: Clinical factors, especially suicidality, predicted psychiatric admission. Admission rates for youths with suicidality were significantly higher in this study than previously reported, suggesting the availability of child psychiatrists in this ED allowed greater ascertainment of suicide risk (and thus hospitalization to mitigate that risk) than occurs in EDs without such staffing.

The present study examined 115 service providers' adherence to components of cognitive-behavioral therapy (CBT) for youth anxiety prior to training, post workshop training, and after three months of weekly consultation. Adherence was measured using a role-play with a trained actor. We examined differences in individual adherence to CBT components across time and the relationship between number of consultation sessions attended and adherence ratings following consultation. Findings indicated that somatic arousal identification and relaxation were the most used treatment components prior to training. Adherence to all components of CBT increased following workshop training, except the usage of problem-solving. Adherence to problem-solving, positive reinforcement, the identification of anxious self-talk, and the creation of coping thoughts increased following consultation but usage of problem-solving remained low compared to other treatment components. Overall adherence remained less than optimal at the final measurement point. Number of consultation sessions attended predicted post-consultation adherence to identification of somatic arousal, identification of anxious self-talk, and positive reinforcement. Implications include tailoring future training based on baseline levels of adherence and spending more time during training and consultation on underutilized CBT components, such as problem-solving. Limitations of the present study, including how adherence was measured, are discussed. This study adds to the implementation science literature by providing more nuanced information on changes in adherence over the course of training and consultation of service providers.

When animals and their offspring are threatened, parents switch from self-defense to offspring protection. How self-defense is suppressed remains elusive. We postulated that suppression of the self-defense response, freezing, is gated via oxytocin acting in the centro-lateral amygdala (CeL). We found that rat dams conditioned to fear an odor, froze when tested alone, whereas if pups were present, they remained in close contact with them or targeted the threat. Furthermore, blocking oxytocin signaling in the CeL prevented the suppression of maternal freezing. Finally, pups exposed to the odor in the presence of the conditioned dam later froze when re-exposed alone. However, if oxytocin signaling in the dam had been blocked, pups failed to learn. This study provides a functional role for the well-described action of oxytocin in the central amygdala, and demonstrates that self-defense suppression allows for active pup protection and mother-pup interactions crucial for pup threat learning.

Exposure to trauma is a common event in the lives of children and adolescents living in the United States. Although a minority of youth develop full posttraumatic stress disorder (PTSD) after a traumatic event, those who do tend to have an extended course of symptoms in multiple functional domains and higher rates of psychiatric comorbidities. Pediatric PTSD can play an important role in legal settings, and requires that an expert witness be well versed in advances in clinical and conceptual models of this diagnosis and familiar with current research devoted to the posttraumatic response in youth. This review is designed to be a resource for the forensic evaluator and outlines the current understanding of epidemiological and clinical features of pediatric PTSD, as well as the neurobiological, dimensional, and developmental conceptual models that describe it.

Since the Third Edition, the Diagnostic and Statistical Manual of Mental Disorders (DSM) has increasingly incorporated developmentally informed criteria for posttraumatic stress disorder (PTSD) because of recognition that children and adolescents can manifest PTSD differently from adults. The most recent edition, DSM-5, among other changes, has introduced a developmental subtype for children six years of age or younger. As pediatric PTSD features very prominently in both civil and criminal proceedings, it is vital that the expert witness be familiar with the updated criteria and know how to interview traumatized youth appropriately in the forensic setting. In this review, we discuss the importance of the evolution of PTSD from past DSM editions to the current one, and the implications of using the new diagnostic criteria and current conceptual models in the forensic evaluation of pediatric PTSD.

PURPOSE/BACKGROUND: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist d-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia. METHODS/PROCEDURES: Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance. FINDINGS/RESULTS: No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments. IMPLICATIONS/CONCLUSIONS: These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early interventions that can potentially ameliorate the defining deficits of ASD and improve long-term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% [95% confidence interval (CI), 62.9 to 100], correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified [specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3)]. These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD.

The purpose of this longitudinal study was to examine the relations of early socialization of anger with change in adolescent depression, and moderation by child anger. Using a sample of low-income, ethnic minority children at familial risk for psychopathology in the United States (n = 92; ages 3-5; 53% female; 65% African American; 27% Latina/o), early anger socialization (i.e., parent response to child anger) was tested as a predictor of change in depression from preadolescence to adolescence [i.e., age 8 (n = 63), 11 (n = 58), and 13 (n = 44)]. A videotaped parent-child interaction was coded for parental socialization of preschooler anger, and psychiatric interviews of depression were conducted three times across preadolescence and adolescence. Major depression diagnoses increased from preadolescence to adolescence. Latent growth modeling indicated parent discouragement of child anger was a significant predictor of an increase in the child's later depression from preadolescence to adolescence, and child anger intensity was a significant moderator.