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An independent validation was conducted of the Utah Autism and Developmental Disabilities Monitoring Network's (UT-ADDM) classification of children with autism spectrum disorder (ASD). UT-ADDM final case status (n = 90) was compared with final case status as determined by independent external expert reviewers (EERs). Inter-rater reliability (ICC = 0.84), specificity [0.83 (95 % CI 0.74-0.90)], and sensitivity [0.99 (95 % CI 0.96-1.00)] were high for ASD case versus non-case classification between UT-ADDM and EER. At least one EER disagreed with UT-ADDM on ASD final case status on nine out of 30 records; however, all three EERs disagreed with UT-ADDM for only one record. Findings based on limited data suggest that children with ASD as identified by UT-ADDM are consistently classified as ASD cases by independent autism experts.

Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12,000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion. A number of medical conditions co-occur with suicide, including asthma, and this study was undertaken to identify genetic risk common to asthma and suicide. This study tests the hypothesis that a particular comorbid condition may identify a more homogeneous genetic subgroup, facilitating the identification of specific genetic risk factors in that group. From pedigrees at increased risk for suicide, we identified three pedigrees also at significantly increased familial risk for asthma. Five suicide decedents from each of these pedigrees, plus an additional three decedents not from these pedigrees with diagnosed asthma, and 10 decedents with close relatives with asthma were genotyped. Results were compared with 183 publicly available unaffected control exomes from 1000 Genomes and CEPH (Centre d'etude du polymorphisme humain) samples genotyped on the same platform. A further 432 suicide decedents were also genotyped as non-asthma suicide controls. Genotyping was done using the Infinium HumanExome BeadChip. For analysis, we used the pedigree extension of Variant Annotation, Analysis and Search Tool (pVAAST) to calculate the disease burden of each gene. The Phenotype Driven Variant Ontological Re-ranking tool (Phevor) then re-ranked our pVAAST results in context of the phenotype. Using asthma as a seed phenotype, Phevor traversed biomedical ontologies and identified genes with similar biological properties to those known to result in asthma. Our top associated genes included those related to neurodevelopment or neural signaling (brain-derived neurotrophic factor (BDNF), neutral sphingomyelinase 2 (SMPD2), homeobox b2 (HOXB2), neural cell adhesion molecule (NCAM2), heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0)), inflammation (free fatty acid receptor 2 (FFAR2)) and inflammation with additional evidence of neuronal involvement (oxidized low density lipoprotein receptor 1 (OLR1), toll-like receptor 3 (TLR3)). Of particular interest, BDNF has been previously implicated in both psychiatric disorders and asthma. Our results demonstrate the utility of combining pedigree and co-occurring phenotypes to identify rare variants associated with suicide risk in conjunction with specific co-occurring conditions.

Importance: The DSM-5 contains revised diagnostic criteria for autism spectrum disorder (ASD) from the DSM-IV-TR. Potential impacts of the new criteria on ASD prevalence are unclear., Objective: To assess potential effects of the DSM-5 ASD criteria on ASD prevalence estimation by retrospectively applying the new criteria to population-based surveillance data collected for previous ASD prevalence estimation., Design, Setting, and Participants: Cross-sectional, population-based ASD surveillance based on clinician review of coded behaviors documented in children's medical and educational evaluations from 14 geographically defined areas in the United States participating in the Autism and Developmental Disabilities Monitoring (ADDM) Network in 2006 and 2008. This study included 8-year-old children living in ADDM Network study areas in 2006 or 2008, including 644 883 children under surveillance, of whom 6577 met surveillance ASD case status based on the DSM-IV-TR., Main Outcomes and Measures: Proportion of children meeting ADDM Network ASD criteria based on the DSM-IV-TR who also met DSM-5 criteria; overall prevalence of ASD using DSM-5 criteria., Results: Among the 6577 children classified by the ADDM Network as having ASD based on the DSM-IV-TR, 5339 (81.2%) met DSM-5 ASD criteria. This percentage was similar for boys and girls but higher for those with than without intellectual disability (86.6% and 72.5%, respectively; P < .001). A total of 304 children met DSM-5 ASD criteria but not current ADDM Network ASD case status. Based on these findings, ASD prevalence per 1000 for 2008 would have been 10.0 (95% CI, 9.6-10.3) using DSM-5 criteria compared with the reported prevalence based on DSM-IV-TR criteria of 11.3 (95% CI, 11.0-11.7)., Conclusions and Relevance: Autism spectrum disorder prevalence estimates will likely be lower under DSM-5 than under DSM-IV-TR diagnostic criteria, although this effect could be tempered by future adaptation of diagnostic practices and documentation of behaviors to fit the new criteria.

Background: The rising population of individuals identified with an autism spectrum disorder (ASD) calls for further investigation of its underlying etiology. A disturbance in the fetal steroid hormone environment may be a mechanism in which environmental and genetic risk factors interact. The mother, fetus, and placenta collectively create the fetal steroid environment. Prepregnancy BMI and pregnancy weight gain have served as markers for fetal steroid hormone exposure in other disease states. This study's objective is to determine whether prepregnancy BMI and pregnancy weight gain are associated with increased ASD risk across study designs and cohorts while controlling for important confounding variables., Methods: A population-based Utah ASD cohort (n = 128) was ascertained in a 3-county surveillance area and gender- and age-matched to 10,920 control subjects. A second, research-based ASD cohort of Utah children (n = 288) and their unaffected siblings (n = 493) were ascertained through participation in an ASD genetics study. Prenatal variables were obtained from birth certificate records., Results: ASD risk was significantly associated with pregnancy weight gain (adjusted odds ratio = 1.10, 95% confidence interval: 1.03 to 1.17; adjusted odds ratio = 1.17, 95% confidence interval: 1.01 to 1.35 for each 5 pounds of weight gained), but not prepregnancy BMI, in population and research-based cohorts, respectively. When analyses were restricted to ASD cases with normal IQ, these associations remained significant., Conclusions: ASD risk associated with a modest yet consistent increase in pregnancy weight gain suggests that pregnancy weight gain may serve as an important marker for autism's underlying gestational etiology. This justifies an investigation into phenomena that link pregnancy weight gain and ASD independent of prepregnancy BMI.

Prenatal and perinatal risk factors associated with intellectual disability (ID) were studied in 8-year-old Utah children from a 1994 birth cohort (N  =  26,108) using broad ascertainment methods and birth records following the most current recording guidelines. Risk factor analyses were performed inclusive and exclusive of children with a known or suspected underlying genetic disorder. Risk factors identified were poly/oligohydramnios, advanced paternal/maternal age, prematurity, fetal distress, premature rupture of membranes, primary/repeat cesarean sections, low birth weight, assisted ventilation greater than 30 min, small-for-gestational age, low Apgar scores, and congenital infection. Although several risk factors lost significance once children with underlying genetic disorders were excluded, socioeconomic variables were among those that maintained a prominent association with increased ID risk.

Background: The objective of this study was to identify psychiatric symptom patterns reported by individuals with phenylketonuria (PKU) in the outpatient clinic setting., Methods: Brief Symptom Inventory (BSI) results, phenylalanine (phe) levels, and demographic information were collected through a retrospective chart review on 64 participants in the study, "A Diversified Approach for PKU Treatment" (ADAPT)., Results: The number of BSI scores meeting clinical threshold was significantly elevated for all global indexes and 6 out of 7 symptom subscales in patients with PKU. Recent and mean phe levels were correlated with age at the time of screening (R(2)=0.10, R(2)=0.10, respectively; p<0.05). Psychoticism and the Positive Symptom Distress Index (PSDI) scores were associated with metabolic control., Conclusions: The results of this study demonstrate a positive correlation between phe levels and psychiatric symptom severity in individuals with PKU., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study examined changes in the administrative prevalence of autism spectrum disorders (ASD) in Utah children from 2002 to 2008 by record source (school and health), age (four, six, and eight), and special education classification. Prevalence increased 100% with 1 in 77 children aged eight identified with ASD by 2008. Across study years and age groups rates were higher when health and school data were combined with a greater proportion of cases ascertained from health. The proportion of children with both a health ASD diagnosis and a special education autism classification did not significantly change. Most children with an ASD health diagnosis did not have an autism special education classification. Findings highlight the growing health and educational impact of ASD.