Faculty Bibliography

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.

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.

Family socioeconomic status (SES) is strongly associated with children's cognitive development, and past studies have reported socioeconomic disparities in both neurocognitive skills and brain structure across childhood. In other studies, bilingualism has been associated with cognitive advantages and differences in brain structure across the lifespan. The aim of the current study is to concurrently examine the joint and independent associations between family SES and dual-language use with brain structure and cognitive skills during childhood. A subset of data from the Pediatric Imaging, Neurocognition and Genetics (PING) study was analyzed; propensity score matching established an equal sample (N = 562) of monolinguals and dual-language users with similar socio-demographic characteristics (M_age = 13.5, Range = 3-20 years). When collapsing across all ages, SES was linked to both brain structure and cognitive skills. When examining differences by age group, brain structure was significantly associated with both income and dual-language use during adolescence, but not earlier in childhood. Additionally, in adolescence, a significant interaction between dual-language use and SES was found, with no difference in cortical surface area (SA) between language groups of higher-SES backgrounds but significantly increased SA for dual-language users from lower-SES families compared to SES-matched monolinguals. These results suggest both independent and interacting associations between SES and dual-language use with brain development. To our knowledge, this is the first study to concurrently examine dual-language use and socioeconomic differences in brain structure during childhood and adolescence.

OBJECTIVE:The serotonin (5-hydroxytryptamine [HT]) system has long been implicated in autism spectrum disorder (ASD). Whole-blood 5-HT level (WB5-HT) is a stable, heritable biomarker that is elevated in more than 25% of children with ASD. Recent findings indicate that the maternal 5-HT system may influence embryonic neurodevelopment, but maternal WB5-HT has not been examined in relation to ASD phenotypes. METHOD:WB5-HT levels were obtained from 181 individuals (3-27 years of age) diagnosed with ASD, 99 of their fathers, and 119 of their mothers. Standardized assessments were used to evaluate cognitive, behavioral, and language phenotypes. RESULTS: = 17.394, p < .001). Paternal and proband WB5-HT did not differ between classes. CONCLUSION:Maternal WB5-HT is associated with neurodevelopmental outcomes in offspring with ASD. Prospective, longitudinal studies will be needed to better understand the relationship between the function of the maternal serotonin system during pregnancy and brain development. Further studies in animal models may be able to reveal the mechanisms underlying these findings.

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.

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.

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.

Structural and functional elements of biological systems are highly conserved across vertebrates. Many neurological and psychiatric conditions affect both humans and animals. A cross-species approach to the study of brain and behaviour can advance our understanding of human disorders via the identification of unrecognized natural models of spontaneous disorders, thus revealing novel factors that increase vulnerability or resilience, and via the assessment of potential therapies. Moreover, diagnostic and therapeutic advances in human neurology and psychiatry can often be adapted for veterinary patients. However, clinical and research collaborations between physicians and veterinarians remain limited, leaving this wealth of comparative information largely untapped. Here, we review pain, cognitive decline syndromes, epilepsy, anxiety and compulsions, autoimmune and infectious encephalitides and mismatch disorders across a range of animal species, looking for novel insights with translational potential. This comparative perspective can help generate novel hypotheses, expand and improve clinical trials and identify natural animal models of disease resistance and vulnerability.