Cardiovascular risk and emotion regulation contribute to depression symptomatology in middle-aged and older autistic adults

Background: Cardiovascular risk factors (CVRF) and executive function difficulties increase during later-life and are associated with depression symptoms among non-autistic older people. These associations, however, have not yet been explored among middle-aged and older autistic people. Methods: Using data collected via Simons Foundation Powering Autism Research (SPARK), Research Match, we examined the frequency of CVRF, and associations between CVRF, executive function and depression symptoms in 387 middle-aged and older autistic people (aged 40-83 years). Results: Autistic adults reported high rates of CVRF (two, 28.9%; three or more, 23.2%). Rates of high cholesterol and obesity were greater among middle-aged and older autistic adults compared to the general population. CVRF, age, and emotion regulation (but not inhibitory control), were significantly associated with depression symptoms in middle-aged and older autistic adults. Conclusions: CVRF occur at high rates in middle-aged and older autistic adults, and it is important that healthcare providers monitor risk factors in order to implement preventative strategies. CVRF are associated with depressive symptoms among middle-aged and older autistic adults, but may not be as important as difficulties with emotion regulation

Cardiovascular disease risk factors in autistic adults: The impact of sleep quality and antipsychotic medication use

Approximately 40% of American adults are affected by cardiovascular disease (CVD) risk factors (e.g., high blood pressure, high cholesterol, diabetes, and overweight or obesity), and risk among autistic adults may be even higher. Mechanisms underlying the high prevalence of CVD risk factors in autistic people may include known correlates of CVD risk factors in other groups, including high levels of perceived stress, poor sleep quality, and antipsychotic medication use. A sample of 545 autistic adults without intellectual disability aged 18+ were recruited through the Simons Foundation Powering Autism Research, Research Match. multiple linear regression models examined the association between key independent variables (self-reported perceived stress, sleep quality, and antipsychotic medication use) and CVD risk factors, controlling for demographic variables (age, sex assigned at birth, race, low-income status, autistic traits). Overall, 73.2% of autistic adults in our sample had an overweight/obesity classification, 45.3% had high cholesterol, 39.4% had high blood pressure, and 10.3% had diabetes. Older age, male sex assigned at birth, and poorer sleep quality were associated with a higher number of CVD risk factors. Using antipsychotic medications was associated with an increased likelihood of having diabetes. Poorer sleep quality was associated with an increased likelihood of having an overweight/obesity classification. Self-reported CVD risk factors are highly prevalent among autistic adults. Both improving sleep quality and closely monitoring CVD risk factors among autistic adults who use antipsychotic medications have the potential to reduce risk for CVD

Germline TERT promoter mutations are rare in familial melanoma.

Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that a rare promoter variant of TERT (c.-57 T>G) is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families. The identification of POT1 and TERT germline mutations highlights the importance of telomere integrity in melanoma biology.The authors would like to thank the families for their willingness to participate; and Rajiv Kumar for the provision of mutation positive samples. The collection of samples in the UK population-ascertained sample set was funded by Cancer Research UK (awards C588/A19167 and C8216/A6129) and by the NIH (CA83115). The work of N.A.G. and R.v.D was supported by the Dutch Cancer Society (UL 2012-5489). D.J.A and C.D.R.E are supported by Cancer Research UK, ERC Combat Cancer and the Wellcome Trust. N.K.H is supported by a fellowship from the National Health and Medical Research Council of Australia. A.M.D. and K.A.P. were supported by CRUK grant (C8197/A16565) and The Isaac Newton Trust. K.M.B. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10689-015-9841-

Psychometric properties of the mock interview rating scale for autistic transition-age youth

BackgroundEmployment is a major contributor to quality of life. However, autistic people are often unemployed and underemployed. One potential barrier to employment is the job interview. However, the availability of psychometrically-evaluated assessments of job interviewing skills is limited for autism services providers and researchers.ObjectiveWe analyzed the psychometric properties of the Mock Interview Rating Scale that was adapted for research with autistic transition-age youth (A-MIRS; a comprehensive assessment of video-recorded job interview role-play scenarios using anchor-based ratings for 14 scripted job scenarios).MethodsEighty-five transition-age youth with autism completed one of two randomized controlled trials to test the effectiveness of two interventions focused on job interview skills. All participants completed a single job interview role-play at pre-test that was scored by raters using the A-MIRS. We analyzed the structure of the A-MIRS using classical test theory, which involved conducting both exploratory and confirmatory factor analyzes, Rasch model analysis and calibration techniques. We then assessed internal consistency, inter-rater reliability, and test–retest reliability. Pearson correlations were used to assess the A-MIRS’ construct, convergent, divergent, criterion, and predictive validities by comparing it to demographic, clinical, cognitive, work history measures, and employment outcomes.ResultsResults revealed an 11-item unidimensional construct with strong internal consistency, inter-rater reliability, and test–retest reliability. Construct [pragmatic social skills (r = 0.61, p &lt; 0.001), self-reported interview skills (r = 0.34, p = 0.001)], divergent [e.g., age (r = −0.13, p = 0.26), race (r = 0.02, p = 0.87)], and predictive validities [competitive employment (r = 0.31, p = 0.03)] received initial support via study correlations, while convergent [e.g., intrinsic motivation (r = 0.32, p = 0.007), job interview anxiety (r = −0.19, p = 0.08)] and criterion [e.g., prior employment (r = 0.22, p = 0.046), current employment (r = 0.21, p = 0.054)] validities were limited.ConclusionThe psychometric properties of the 11-item A-MIRS ranged from strong-to-acceptable, indicating it may have utility as a reliable and valid method for assessing the job interview skills of autistic transition-age youth

POT1 mutations predispose to familial melanoma

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease. Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.D.J.A., C.D.R.-E., Z.D., J.Z.L., J.C.T., M.P. and T.M.K. were supported by Cancer Research UK and the Wellcome Trust (WT098051). C.D.R.-E. was also supported by the Consejo Nacional de Ciencia y Tecnología of Mexico. K.A.P. and A.M.D. were supported by Cancer Research UK (grants C1287/A9540 and C8197/A10123) and by the Isaac Newton Trust. N.K.H. was supported by a fellowship from the National Health and Medical Research Council of Australia (NHMRC). L.G.A. was supported by an Australia and New Zealand Banking Group Limited Trustees PhD scholarship. A.L.P. is supported by Cure Cancer Australia. The work was funded in part by the NHMRC and Cancer Council Queensland. The work of N.A.G. was in part supported by the Dutch Cancer Society (UL 2012-5489). M.H., J.A.N.-B. and D.T.B. were supported by Cancer Research UK (programme awards C588/A4994 and C588/A10589 and the Genomics Initiative). C.L.-O., A.J.R. and V.Q. are funded by the Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII), the Red Temática de Investigación del Cáncer (RTICC) del ISCIII and the Consolider-Ingenio RNAREG Consortium. C.L.-O. is an investigator with the Botín Foundation.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.294

A Multi-Site Analysis of the Prevalence of Food Insecurity in the United States, before and during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs. Objective: The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements. This study presents results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic. Methods: A validated survey instrument was developed and implemented in whole or part through an online survey of adults across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA 6-item module. Food security prevalence was analyzed using ANOVA by sampling method to assess statistically significant differences. Results: Respondents (n = 27,168) indicate higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, compared with before the pandemic. In nearly all study sites, there is a higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. The findings demonstrate lingering food insecurity, with high prevalence over time in sites with repeat cross-sectional surveys. There are no statistically significant differences between convenience and representative surveys, but a statistically higher prevalence of food insecurity among high-risk compared with convenience surveys. Conclusions: This comprehensive study demonstrates a higher prevalence of food insecurity in the first year of the COVID-19 pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations. Results especially document the continued high levels of food insecurity, as well as the variability in estimates due to the survey implementation method

Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant

(BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype.Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation

Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder

Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic treatment for veterans with PTSD. Extensive work has identified epigenetic factors related to PTSD disease risk and pathophysiology, but how these factors influence treatment response is unclear. Serotonin signaling and hypothalamic-pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are molecular pathways targeted by PTSD treatments. To identify potential biomarkers for treatment response, we utilized genomic DNA isolated from peripheral blood samples from veterans with PTSD who were responders (n = 11) or non-responders (n = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements suggested to regulate this gene. Selected subjects were matched across MBSR responder status by baseline symptoms, age, sex, current smoking status, and current antidepressant use. Percent methylation was compared between responders and non-responders at baseline (pre-MBSR treatment). Additionally, percent change in methylation from baseline to post-treatment was compared between responders and non-responders. There was a significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2 [F(1, 19) = 7.492, p = 0.013] whereby responders had a decrease in methylation and non-responders had an increase in methylation from before to after treatment in this region. Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 [F(1, 19) = 5.551, p = 0.029] which resides in a known glucocorticoid response element (GRE). Decreases in FKBP5 methylation after treatment in responders as compared to increases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. These preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of response to meditation treatment in PTSD and require validation in larger cohorts