Faculty Bibliography

Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD.

The examination of functional connectivity in fMRI data collected during task-free "rest" has provided a powerful tool for studying functional brain organization. Limitations of this approach include susceptibility to head motion artifacts and participant drowsiness or sleep. These issues are especially relevant when studying young children or clinical populations. Here we introduce a movie paradigm, Inscapes, that features abstract shapes without a narrative or scene-cuts. The movie was designed to provide enough stimulation to improve compliance related to motion and wakefulness while minimizing cognitive load during the collection of functional imaging data. We compare Inscapes to eyes-open rest and to age-appropriate movie clips in healthy adults (Ocean's Eleven, n=22) and a pilot sample of typically developing children ages 3-7 (Fantasia, n=13). Head motion was significantly lower during both movies relative to rest for both groups. In adults, movies decreased the number of participants who self-reported sleep. Intersubject correlations, used to quantify synchronized, task-evoked activity across movie and rest conditions in adults, involved less cortex during Inscapes than Ocean's Eleven. To evaluate the effect of movie-watching on intrinsic functional connectivity networks, we examined mean functional connectivity using both whole-brain functional parcellation and network-based approaches. Both inter- and intra-network metrics were more similar between Inscapes and Rest than between Ocean's Eleven and Rest, particularly in comparisons involving the default network. When comparing movies to Rest, the mean functional connectivity of somatomotor, visual and ventral attention networks differed significantly across various analyses. We conclude that low-demand movies like Inscapes may represent a useful intermediate condition between task-free rest and typical narrative movies while still improving participant compliance. Inscapes is publicly available for download at headspacestudios.org/inscapes.

Catatonia is a syndrome heterogeneous with regard to presentation and etiology. Electroconvulsive therapy (ECT) remains the first-line treatment for catatonia. Literature review reveals only a few published case reports on the use of right unilateral (RUL) ECT in catatonia, 1 case report on ultrabrief RUL ECT, and an absence of evidence on the relative effectiveness and tolerability of RUL versus bilateral ECT in treating catatonia. In contrast, there are multiple reports in the literature of robustly dosed bilateral ECT, often administered on consecutive days. Reasons for choosing this intervention over the better-tolerated RUL treatment include assumptions about its relative speed and/or breadth of efficacy. Here we present a case series of 13 catatonic patients treated in an academic center over the course of the last 3 years. Our experience suggests that ultrabrief RUL ECT can rapidly and effectively treat catatonia from diverse etiologies.

Introduction: The objective of this study was to use two interventions to decrease PTSD and PTSD symptomatology in young burned children as measured by the Posttraumatic Stress Disorder Semi-Structured Interview and Observational Report, or PTSDSSI (Sheeringa et al., 1994; 2003). The PTSDSSI was an appropriate instrument for evaluating PTSD in young children because its use elsewhere informed the DSM 5 diagnostic subtype, "PTSD in Children 6 Years and Younger" (APA, 2013). The PTSDSSI also requires parent observation of symptoms appropriate for young children-such as children's posttraumatic play, distressing dreams, withdrawal and irritibility; with a maximal score of 38. The Intervention group in this study received either the DEF (Distress, Emotional Support, and Family Functioning protocol) or the DEF+COPE (Creating Opportunities for Parent Empowerment program). Outcomes of child stress were compared with a Non-Intervention, control group. Methods: Children aged 0-5 years old admitted for an acute burn or for reconstructive surgery and their families, who speak English or Spanish, were eligible. The DEF consists of an initial meeting with caregivers to identify distress or support from an interview and offer clinical referrals for the family, and can be found online on nctsnet.org. The COPE (Melnyk, 2004) provides a workbook to increase parents' knowledge of typical behaviors and emotions children display in hospital and advice on how to participate more directly in child's care. Parents completed the PTSDSSI after their child's admission and at 6 month follow-up, to measure child stress. The 6-month change scores of the PTSDSSI were analyzed for three symptom clusters: re-experiencing(B), numbing/avoidance(C), and hyperarousal(D). Results: Although results did not reach statistical significance in this small sample, there was a clear trend of larger decreases in PTSD symptoms for children in the intervention group as compared to children in the control group. Conclusions: Both forms of intervention appear to have aided in the reduction child stress as measured by the PTSDSSI. Future studies with larger samples should explore both types of intervention. Applicability of Research to Practice: The psychosocial interventions outlined have clear benefits that should be taken into consideration when providing care to children with burns. (Figure presented)

Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders.