Amanda V. Bakian

Potential Impact of DSM-5 Criteria on Autism Spectrum Disorder Prevalence Estimates

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 childrens 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.

Acute Air Pollution Exposure and Risk of Suicide Completion

Research into environmental factors associated with suicide has historically focused on meteorological variables. Recently, a heightened risk of suicide related to short-term exposure to airborne particulate matter was reported. Here, we examined the associations between short-term exposure to nitrogen dioxide, particulate matter, and sulfur dioxide and completed suicide in Salt Lake County, Utah (n = 1,546) from 2000 to 2010. We used a time-stratified case-crossover design to estimate adjusted odds ratios for the relationship between suicide and exposure to air pollutants on the day of the suicide and during the days preceding the suicide. We observed maximum heightened odds of suicide associated with interquartile-range increases in nitrogen dioxide during cumulative lag 3 (average of the 3 days preceding suicide; odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.04, 1.39) and fine particulate matter (diameter ≤2.5 μm) on lag day 2 (day 2 before suicide; OR = 1.05, 95% CI: 1.01, 1.10). Following stratification by season, an increased suicide risk was associated with exposure to nitrogen dioxide during the spring/fall transition period (OR = 1.35, 95% CI: 1.09, 1.66) and fine particulate matter in the spring (OR = 1.28, 95% CI: 1.01, 1.61) during cumulative lag 3. Findings of positive associations between air pollution and suicide appear to be consistent across study locations with vastly different meteorological, geographical, and cultural characteristics.

Changes in the administrative prevalence of autism spectrum disorders: contribution of special education and health from 2002-2008.

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.

Maternal Prenatal Weight Gain and Autism Spectrum Disorders

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.

CACHE-SITE SELECTION IN CLARK'S NUTCRACKER (NUCIFRAGA COLUMBIANA)

ABSTRACT. Clarks Nutcracker (Nucifraga columbiana) is one of the most specialized scatter-hoarding birds, considered a seed disperser for four species of pines (Pinus spp.), as well as an obligate coevolved mutualist of Whitebark Pine (P. albicaulis). Cache-site selection has not been formally studied in Clarks Nutcrackers, which are considered effective seed dispersers for pines because past studies have found that they harvest and store large quantities of seeds. Although many seeds are placed in sites suitable for germination and establishment, information is lacking on the proportions of seeds placed in suitable versus unsuitable sites. We used radiotelemetry to investigate cache-site selection and evaluate the suitability of selected cache sites for establishment of Whitebark and Ponderosa (P. ponderosa) pines. On a landscape scale, Clarks Nutcrackers cached seeds centrally within home ranges, even though this required them to transport seeds up to 32.6 km. They selected low-elevation forests for caching, presumably because these sites accumulated little snow. When caching at high elevations, the birds placed most seeds in aboveground microsites. Only 15% of Whitebark Pine seed caches (n = 155 caches) were placed below ground and in habitats where seeds could germinate and seedlings grow. For comparative purposes, 42% of Ponderosa Pine seed caches were placed in suitable habitats and below ground. Although Whitebark Pine is an obligate mutualist of Clarks Nutcracker, our study suggests that Clarks Nutcrackers in some populations may be more effective seed dispersers for Ponderosa Pine than for Whitebark Pine.

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury

Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

Prenatal and Perinatal Factors Associated with Intellectual Disability.

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.

A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980s Utah/UCLA Autism Epidemiologic Study

This study describes medical conditions experienced by a population-based cohort of adults with autism spectrum disorder whose significant developmental concerns were apparent during childhood. As part of a 25-year outcome study of autism spectrum disorder in adulthood, medical histories were collected on 92 participants (N = 69 males) who were first ascertained as children in the mid-1980s, 11 of whom were deceased at the time of follow-up. Questionnaires queried medical symptoms, disorders, hospitalizations, surgeries, and medication use. Median age at follow-up was 36 years (range: 23.5–50.5 years), and intellectual disability co-occurred in 62%. The most common medical conditions were seizures, obesity, insomnia, and constipation. The median number of medical conditions per person was 11. Increased medical comorbidity was associated with female gender (p = 0.01) and obesity (p = 0.03), but not intellectual disability (p = 0.79). Adults in this cohort of autism spectrum disorder first ascertained in the 1980s experience a high number of chronic medical conditions, regardless of intellectual ability. Understanding of these conditions commonly experienced should direct community-based and medical primary care for this population.

Sociodemographic risk factors associated with autism spectrum disorders and intellectual disability

This study examined the hypotheses that (1) sociodemographic risk factors in young children with autism spectrum disorders (ASD) and/or intellectual disability (ID) significantly vary by disability type, and (2) measures of income (mean adjusted gross income, mean federal taxes paid, and mean tax exemptions) significantly increase between 1994 and 2002, and are lower in families with a child with ASD and/or ID compared with the general population. A multiple source surveillance system utilizing a retrospective record review was used to identify ASD and ID cases from a population of 26,108 eight‐year‐old children born in 1994 and living in Utah in 2002. ASD without ID (ASD‐only, n = 99) cases were significantly more likely to be male (P<0.01) and have mothers of White non‐Hispanic ethnicity (P = 0.02). ASD with ID (ASD/ID, n = 33) cases were significantly more likely to be male (P<0.01) and have mothers older than 34 years (P = 0.03). ID without ASD (ID‐only, n = 113) cases were significantly more likely to have fathers older than 34 years (P<0.01) and were significantly less likely to have mothers with >13 years education (P<0.01). Measures of income for cases at birth and at 8 years of age were not significantly lower than the general population and mean adjusted income of cases significantly increased from birth to 8 years of age. Investigations focused on defining early sociodemographic risk factors by different endophenotypes of ASD may assist in identifying risk factors for this complex group of neurodevelopmental disorders. Aggregate tax information may be a unique resource to utilize for population‐based analysis. Autism Res 2011,4:438–448.

Genetic risk factors in two Utah pedigrees at high risk for suicide

We have used unique population-based data resources to identify 22 high-risk extended pedigrees that show clustering of suicide over twice that expected from demographically adjusted incidence rates. In this initial study of genetic risk factors, we focused on two high-risk pedigrees. In the first of these (pedigree 12), 10/19 (53%) of the related suicides were female, and the average age at death was 30.95. In the second (pedigree 5), 7/51 (14%) of the suicides were female and the average age at death was 36.90. Six decedents in pedigree 12 and nine in pedigree 5 were genotyped with the Illumina HumanExome BeadChip. Genotypes were analyzed using the Variant Annotation, Analysis, and Search program package that computes likelihoods of risk variants using the functional impact of the DNA variation, aggregative scoring of multiple variants across each gene and pedigree structure. We prioritized variants that were: (1) shared across pedigree members, (2) rare in other Utah suicides not related to these pedigrees, (3) ⩽ 5% in genotyping data from 398 other Utah population controls and (4) ⩽5% frequency in publicly available sequence data from 1358 controls and/or in dbSNP. Results included several membrane protein genes (ANO5, and TMEM141 for pedigree 12 and FAM38A and HRCT1 for pedigree 5). Other genes with known neuronal involvement and/or previous associations with psychiatric conditions were also identified, including NFKB1, CASP9, PLXNB1 and PDE11A in pedigree 12, and THOC1, and AUTS2 in pedigree 5. Although the study is limited to variants included on the HumanExome BeadChip, these findings warrant further exploration, and demonstrate the utility of this high-risk pedigree resource to identify potential genes or gene pathways for future development of targeted interventions.