Faculty Bibliography

OBJECTIVES/OBJECTIVE:This study aimed to understand if maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) is associated with delayed language development among very young children ("toddlers"). METHODS:Data were collected from 61 mothers and toddlers (ages 12-42 months, mean age = 25.6 months SD = 8.70). Child expressive and receptive language development was assessed by the Ages and Stages Questionnaire (ASQ) communication subscale (ASQCS) that measures language acquisition. Observed maternal caregiving behavior was coded from videos of 10-min free-play interactions via the CARE-Index. Correlations, Mann-Whitney tests, and multiple linear regression were performed. RESULTS:There was no significant association between maternal IPV-PTSD severity and the ASQCS. Maternal IPV-PTSD severity was associated with continuous maternal behavior variables (i.e. sensitive and controlling behavior on the CARE-Index) across the entire sample and regardless of child gender. Maternal sensitivity was positively and significantly associated with the ASQCS. Controlling behavior was negatively and significantly associated with the ASQCS. CONCLUSIONS:Results are consistent with the literature that while maternal IPV-PTSD severity is not associated with child language delays, the quality of maternal interactive behavior is associated both with child language development and with maternal IPV-PTSD severity. Further study is needed to understand if the level of child language development contributes to intergenerational risk or resilience for relational violence and/or victimization.

Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.

Venous thromboembolism (VTE), comprised of deep vein thrombosis and pulmonary embolism, is a common health problem both in the United States and worldwide, with significant associated morbidity and mortality. Despite multiple known genetic and situational risk factors, an estimated 30% of all events remain classified as idiopathic, demonstrating a significant knowledge gap in the pathophysiology VTE. While platelets are well established as an essential contributor to thrombus formation and there has been recent interest in the role of neutrophil extracellular traps, specific cell types and pathways involved in the pathogenesis of VTE remain uncertain. In this study, our primary aims were to define a unique transcriptional signature for VTE and to identify the types of cells and specific pathways involved in development of VTE. Whole blood was collected in PAX gene tubes and RNA sequencing for coding mRNA was performed in an unbiased manner in 201 patients with prevalent VTE as well as 43 healthy controls. We used a bioinformatics approach to develop a unique signature for VTE by identifying differentially expressed genes, developing cell-type modules, and ascertaining pathways driving differentially expressed transcripts. We performed additional analyses on subgroups of patients with idiopathic VTE, patients with incident VTE, and VTE patients matched to healthy controls by age and sex. We went on to use machine learning methods to learn models that best differentiate VTE patients from healthy controls and validated it on a left out test set within our VTE population. Genes specific to neutrophils, erythrocytes, and platelets, in that order, were most significantly upregulated in patients with VTE compared to healthy controls. Genes related to T-cells were downregulated. Pathway analysis revealed upregulated neutrophil activation and degranulation, erythrocyte differentiation and homeostasis, and platelet degranulation. A gene signature of 217 transcripts was outstanding at differentiating patients with VTE versus healthy controls (AUC 0.94). Following adjustment for age, sex, and race/ethnicity our genetic signature remained significantly robust at differentiating patients with VTE versus controls (AUC 0.83). Our expression signature remained stable across patients with idiopathic VTE (AUC 0.93), and in patients who went on to develop future VTE events (AUC 0.95). In summary, we have demonstrated a whole blood transcriptional signature for prevalent and incident VTE. Genes related to neutrophils, erythrocytes, and platelets are upregulated in patients with VTE and genes related to T-cells were downregulated. These findings suggest an active role of cell types once thought to be passively entrapped within thrombus and provide new areas of study to establish the pathophysiology of VTE

This study examined how experiences of service denial and discrimination in three health care settings-doctors' offices, emergency rooms, and mental health clinics-might contribute to attempted suicide among transgender adults. Mechanisms of this relationship were examined, including treatment receipt and the use of substances to cope with mistreatment. Perceived emotional social support was also tested as a potential protective factor against the deleterious effects of service denial and discrimination on treatment receipt, substance use, and attempted suicide. The analysis included 4190 respondents from the National Transgender Discrimination Survey. Structural equation modeling was employed to test hypothesized relationships. Being denied a greater number of services and discriminated against in more settings were associated with lower levels of treatment receipt. Service denial was also correlated with increased rates of coping-motivated substance use and elevated rates of attempted suicide. Treatment receipt mediated the relationships between service denial/discrimination and substance use. Substance use mediated the relationship between treatment receipt and attempted suicide. Higher levels of support were protective to treatment receipt when denied services in one setting, but no longer retained protective effects when denied in two or three settings. Results have critical implications for service access and delivery and policies that protect transgender help-seekers in the health care system.

Turban and van Schalkwyk assert in their Translations article, "'Gender Dysphoria' and Autism Spectrum Disorder: Is the Link Real?" that an over-representation of autism spectrum disorder (ASD) in gender dysphoria is unsupported based on current evidence. Turban and van Schalkwyk discuss 7 of the currently 19 available empirical studies (excluding reviews and case reports) of the over-occurrence of ASD and/or autism traits with gender dysphoria/diversity. They are correct to note that some ASD screeners may lack specificity; that is, a clinical-range total score could indicate non-ASD-related mental health conditions or other developmental difference. However, they do not account for the 7 available studies which specifically report rates of clinical diagnoses of ASD among unselected gender-diverse samples. We suggest also that many of the studies that assess ASD-symptoms in gender-diverse groups are more convincing than suggested by Turban and van Schalkwyk because they employ measures assessing the multi-dimensionality of ASD symptoms and report significant elevations not only for socially-related symptoms but also for the various components of restricted and repetitive behaviors and interests (RRBI) core to ASD. We come together to write this response as gender clinicians and researchers, autism clinicians and researchers, and key stakeholders, including autistic and autistic transgender self-advocates. We work and live with the co-occurrence of autism and gender diversity on a daily basis, and we are concerned that perpetuating misunderstanding about the co-occurrence places individuals at risk.

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophrenia cases and 27 healthy controls. Associations between olfaction measures and psychiatric symptoms were also examined. Cases and controls had similar identification accuracy of unpleasant odors, but cases were significantly less accurate in naming pleasant odors. In cases, greater negative symptom severity was related to abnormal hedonic judgments; specifically, higher pleasantness ratings for unpleasant odors and higher unpleasantness ratings for pleasant odors. Greater positive symptom severity was associated with lower pleasantness ratings for neutral odors. Regarding sex differences, male cases and female controls rated pleasant odors as significantly more unpleasant than male controls. Correlations between depression severity and pleasantness ratings of neutral odors were in opposite directions in male and female cases. These results suggest that a normal sexual dimorphism in the circuitry for hedonic odor judgments may interact with schizophrenia pathology, supporting the utility of olfactory hedonics as a sex-specific biomarker of this pathology.

BACKGROUND:Sleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking. OBJECTIVE:We conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD. METHODS:FINDINGS: From a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9. DISCUSSION AND CLINICAL IMPLICATIONS/UNASSIGNED:A number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force created the TASK3 working groups to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve standardization of experimental designs. This article concerns the parameters that can be measured to assess the physiologic condition of the animals that are used to study rodent models of epilepsy. Here we discuss CDEs for physiologic parameters measured in adult rats and mice such as general health status, temperature, cardiac and respiratory function, and blood constituents. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript we discuss the monitoring of different aspects of physiology of the animals. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of biomarkers and new treatments for epilepsy.