# Complex versus Essential Autism: A Developmental Study of Risk

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $688,332

## Abstract

PROJECT SUMMARY/ABSTRACT
In recognition of the developmental heterogeneity of ASD, Miles and colleagues divided ASD into two groups:
"complex autism" and "essential autism". The label "complex autism" grouped together children with ASD who
had overt evidence of abnormalities of early morphogenesis, e.g. as signaled by the presence of multiple
dysmorphic features and/or microcephaly and associated with lower IQs, more seizures, and higher incidence
of EEG and MRI abnormalities. Children with "essential autism", by comparison, had fewer dysmorphic
features, had greater male to female ratios, and showed greater heritability of autism features within families.
An implication of this work was that in complex autism, autism was expected to arise as the result of broad
developmental insult that also impacted social function, whereas essential autism was viewed as the result of
specific social neural systems dysfunction. In this study, we use this conceptualization of complex versus
essential autism to longitudinally track from 6 to 36 months of age two groups of infants with distinct etiologies
but common elevation of autism symptoms: very low birthweight (VLBW, n=100) infants, who, like children with
complex autism, are expected to evidence a broad range of delays in multiple domains, and high-risk infant
siblings of children with ASD (HR-Sibs, n=100), who, as in essential autism, show heightened heritability of
ASD symptoms and greater risk for social and communicative challenges. These groups are compared against
a control group of low-risk typically developing children (LR, n=100). We take promising eye tracking (ET) and
EEG paradigms that have been associated with the emergence of ASD in HR-Sibs in the first year after life
after birth, and which were primarily developed to capture social dimensions of function, and extend them in
order to investigate analogous nonsocial information processing. We hypothesize that VLBW infants
evidencing ASD symptoms will show decreased performance in both social and nonsocial tasks, highlighting
generalized difficulty with information processing consistent with broader developmental risk, whereas we
hypothesize that difficulties in HR-Sibs with similar ASD symptoms will show more specific social (c.f.
nonsocial) atypicalities. By adapting and extending paradigms which have shown strong or unique signal for
later ASD in HR-Sibs, we will further our understanding of mechanisms underlying ASD risk and inform
potential biomarker discovery; by pairing this with different etiological risk groups, we will elucidate multilevel
vulnerabilities that can shape developmental trajectories and the emergence of the disorder. In summary, this
work will advance our understanding of developmental trajectories of risk associated with ASD, elucidate
mechanisms underlying later emergence of core autism features, and help to test and refine the sensitivity and
specificity of putative early neurobehavioral and neurocognitive biomarkers ...

## Key facts

- **NIH application ID:** 9897597
- **Project number:** 5R01MH115913-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** FREDERICK SHIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $688,332
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897597

## Citation

> US National Institutes of Health, RePORTER application 9897597, Complex versus Essential Autism: A Developmental Study of Risk (5R01MH115913-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897597. Licensed CC0.

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