Mental Health Comorbidities in Adolescents with ASD: Indirect Effects of Family Functioning through Youth Social Competence

Mental Health Comorbidities in Adolescents with ASD: Indirect Effects of Family Functioning through Youth Social Competence Marie Johnson, Depts. of Psychology and Product Innovation, and Jessica Greenlee and Cathryn Richmond, Dept. of Psychology Graduate Students, with Dr. Marcia Winter, Dept. of Psychology Recent research has established the high comorbidities of mental health problems in adolescents with Autism Spectrum Disorder (ASD; see Strang, et al., 2012), prompting researchers to examine factors that may contribute to elevated anxiety and depression. Given the centrality during adolescence of both the family and peer contexts (Greenlee, Winter, & Diehl, 2018) as well as the stage salience of peer relationships (Masten et al., 1995), this study focused on family functioning, social competence, and mental health in verbally-fluent adolescents with ASD. Some have suggested that adolescents with ASD who have no cognitive impairment are more interested in social interaction but also more aware of their social differences (Mazurek & Kanne, 2010). Combined with the social demands of adolescence, increased social awareness may put youth at risk for disengaging from peers; poor peer relationships, feelings of isolation, and loneliness have been associated with internalizing problems in youth with ASD (Bauminger & Kasari, 2000; Vickerstaff et al., 2007; Whitehouse et al., 2009). We reasoned that adolescents learn social skills in part from family experiences, even in the context of ASD, and that the family environment plays a role in adolescent’s social competence. Thus, while social-communication deficits are an inherent part of an ASD diagnosis, families still play a role in adolescents’ social competencies and influence their social development. Therefore, we tested part of the larger theoretical model by examining the indirect relationship between family functioning and adolescent anxiety and depression symptomatology via adolescent social competence for adolescents with ASD. This study uses data from the Teens and Parents (TAP) Study (see Greenlee, 2019). Participants were adolescents aged 13-17 (N = 178; Mage= 14.92, SD = 1.31; 73% male) diagnosed with ASD, and their primary caregivers (PCs) who all identified as biological or adoptive mothers. PCs reported demographics and completed (1) the Self-Report of Family Inventory (SFI; Beavers & Hampston, 2000) to assess global family functioning via the Health and Competence subscale, and (2) the Social Responsiveness Scale (SRS; Constantino & Gruber, 2012) to assess deficits in adolescent social competencies. Adolescents reported their own depression and anxiety symptoms via the Revised Children’s Anxiety and Depression Scale-Short Version (RCADS; Ebesutani et al., 2012). As shown in Figures 1 and 2, the indirect pathway from family functioning to social competence deficits and in turn to internalizing symptoms was statistically significant for adolescent anxiety (B= -1.015, SE = 0.394, 95% CI = [-1.893, -0.353]) and depression symptoms (B= -0.513, SE = 0.192, 95% CI = [-0.938, -0.189]) over and above the effects of family SES and adolescent age, sex, and restrictive and repetitive behavior. It was proposed that family functioning would play a role in adolescent mental health symptomatology via the mediating effect of social competence. Results support this hypothesis, indicating the importance of family functioning in youth social competence, and the subsequent effects on adolescent mental health. These results contribute to the understanding of mental health comorbidities in adolescents with ASD and could be used to inform future interventions.https://scholarscompass.vcu.edu/uresposters/1315/thumbnail.jp

A Piece of My Heart: Examining Healing Facilitated by the Performing Arts

Undergraduate Performing Arts - Theatr

Comparison of household measure descriptions and food photographs in determining food portion sizes among young adults.

Background: Portion size estimation is one of the largest sources of error in dietary assessment and relies on individuals’ perception, memory and conceptual skills(1). Varying methods adopted by researchers and practitioners have led to conflicting conclusions on accuracy of current dietary assessment methods including food photography and household measure estimations. There is also an absence of research focusing on young adults in this area. This study aimed to assess the accuracy of portion size estimations using household measures and food photographs compared to actual weights, among young adults. Methods: In a cross-sectional study design, 35 (18 female, 17 male; aged 18–26 years) participants were recruited by posters distributed around a North England university campus. Participants volunteered by arriving at a designated location indicated on the posters. A short demographic questionnaire was completed before participants self- served a meal consisting of three items with either a definite shape (jacket potato) or amorphous foods of no defined shape (baked beans and grated cheese). Serving dishes were weighed before and after serving, providing the actual weight of foods served. Fifteen minutes after eating, a questionnaire was used to collect dietary information. Participants described portions using household measures e.g. number of spoonfuls or ‘small’, ‘medium’ or ‘large’. These were quantified using a portion size reference guide(2). A food photograph atlas(3) was used for selection of a photograph representing each item and the associated weight recorded. In total each participant provided three weights per component (i.e. actual weight, household measure estimate, food photograph estimate) providing 315 weights overall. Results: For the overall meal, household measure estimations were the most accurate with an average 4% underestimation compared to actual weight. Food photographs overestimated portion weight by 14% on average. For individual meal components food photographs were more accurate in estimating the size of jacket potatoes with no significant difference between estimates and actual weights (P = 0.34). Cheese was significantly overestimated by food photographs (P = 0.029) and underestimated by household description (P = 0.005) compared to actual weights. Baked beans were overestimated by both methods. Females overestimated more frequently, however differences in estimation between males and females were not statistically significant. Discussion: Estimated portion weights of all three food components differed significantly to actual weight for at least one of the methods. It would therefore be inappropriate to suggest that either method can assess the dietary intake of young adults without error. Household measure descriptions were closer to actual weight than estimations based on food photographs. Amorphous foods may be particularly prone to overestimation regardless of method. Consideration should be given to the likely overestimation in portion size associated with food photographs and underestimation with household measures. Both under- and over-estimation can be associated with household measure descriptions according to the type of food being assessed. Food photographs and household methods are useful portion size assessment tools for use among young adults only when inherent errors in both methods are acknowledged

Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus

Peer reviewe

Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk

Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al

Research Staff COVID-19 Pandemic Survey-Results from the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network

Objectives: There is a lack of knowledge about the challenges of researchers who continued in-person research during the early phases of the COVID-19 pandemic. Design: Electronic survey assessing work-related exposure to COVID-19, logistical challenges, and procedural changes during the first year of the COVID-19 pandemic on clinical research. Setting: National Heart, Lung, and Blood Institute-sponsored Prevention and Early Treatment of Acute Lung Injury Clinical Trial Network Centers. Subjects: Research staff at research Network Sites. Measurements and Main Results: The 37-question survey was completed by 277 individuals from 24 states between 29 September 2020, and 12 December 2020, yielding a response rate of 37.7%. Most respondents (91.5%) indicated that non-COVID-19 research was affected by COVID-19 research studies. In response to the COVID-19 pandemic, 20% of respondents were reassigned to different roles at their institution. Many survey takers were exposed to COVID-19 (56%), with more than 50% of researchers requiring a COVID-19 test and 8% testing positive. The fear of infection was 2.7-times higher compared to pre-COVID-19 times. Shortages of personal protective equipment were encountered by 34% of respondents, primarily due to lack of access to N95 masks, followed by gowns and protective eyewear. Personal protective equipment reallocation from research to clinical use was reported by 31% of respondents. Most of the respondents (88.5%), despite these logistical challenges, indicated their willingness to enroll COVID-19 patients. Conclusions: During the first year of the COVID-19 pandemic, members of the research network were engaged in COVID-19 research despite logistical challenges, limited access to personal protective equipment, and fear of exposure. The research network’s survey experience can inform ongoing policy discussions to create research enterprises that can dexterously refocus research to address the knowledge gaps associated with novel public health emergencies while mitigating the effect of pandemics on existing research projects and research personnel

GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation.

Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the KATP channel blocker tolbutamide, and the L-type Ca(2+) channel blocker isradipine; however, depolarization was abolished by lowering extracellular Na(+). The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of Na(+)-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca(2+) from thapsigargin-sensitive Ca(2+) stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by β cells.We thank David Wiggins for excellent technical assistance. This work was supported by the Medical Research Council, Diabetes UK (to R. Ramracheya ), Oxford Biomedical Research Centre (to A. Tarasov), the Wellcome Trust (Senior Investigator Awards to A. Galione and P. Rorsman), the Warwick Impact Fund (to C. Weston and G. Ladds), the Biotechnology and Biological Sciences Research Council (to G. Ladds), the Knut and Alice Wallenberg Foundation (to P. Rorsman), and the Swedish Research Council (to P. Rorsman). The initial stages of M. Shigeto’s stay in Oxford were supported by a fellowship from Kawasaki Medical School.This is the final version of the article. It was first available from the American Society for Clinical Investigation via http://dx.doi.org/10.1172/JCI8197

APOΕ4 Lowers Energy Expenditure in Females and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer\u27s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field. METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4. RESULTS: Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis. CONCLUSIONS: Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a \u27Warburg like\u27 endophenotype that is observable in young females decades prior to clinically manifest AD

A Tale of Two Disks: Mapping the Milky Way with the Final Data Release of APOGEE

We present new maps of the Milky Way disk showing the distribution of metallicity ([Fe/H]), $\alpha$-element abundances ([Mg/Fe]), and stellar age, using a sample of 66,496 red giant stars from the final data release (DR17) of the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. We measure radial and vertical gradients, quantify the distribution functions for age and metallicity, and explore chemical clock relations across the Milky Way for the low-$\alpha$ disk, high-$\alpha$ disk, and total population independently. The low-$\alpha$ disk exhibits a negative radial metallicity gradient of $-0.06 \pm 0.001$ dex kpc$^{-1}$, which flattens with distance from the midplane. The high-$\alpha$ disk shows a flat radial gradient in metallicity and age across nearly all locations of the disk. The age and metallicity distribution functions shift from negatively skewed in the inner Galaxy to positively skewed at large radius. Significant bimodality in the [Mg/Fe]-[Fe/H] plane and in the [Mg/Fe]-age relation persist across the entire disk. The age estimates have typical uncertainties of $\sim0.15$ in $\log$(age) and may be subject to additional systematic errors, which impose limitations on conclusions drawn from this sample. Nevertheless, these results act as critical constraints on galactic evolution models, constraining which physical processes played a dominant role in the formation of the Milky Way disk. We discuss how radial migration predicts many of the observed trends near the solar neighborhood and in the outer disk, but an additional more dramatic evolution history, such as the multi-infall model or a merger event, is needed to explain the chemical and age bimodality elsewhere in the Galaxy.Comment: 41 pages, 32 figures, accepted to Ap

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD