Projects per year
Abstract
Metals are critical to neurodevelopment, and dysregulation in early life
has been documented in autism spectrum disorder (ASD). However,
underlying mechanisms and biochemical assays to distinguish ASD cases
from controls remain elusive. In a nationwide study of twins in Sweden,
we tested whether zinc-copper cycles, which regulate metal metabolism,
are disrupted in ASD. Using novel tooth-matrix biomarkers that provide
direct measures of fetal elemental uptake, we developed a predictive
model to distinguish participants who would be diagnosed with ASD in
childhood from those who did not develop the disorder. We replicated our
findings in three independent studies in the United States and the UK.
We show that three quantifiable characteristics of fetal and postnatal
zinc-copper rhythmicity are altered in ASD: the average duration of
zinc-copper cycles, regularity with which the cycles recur, and the
number of complex features within a cycle. In all independent study sets
and in the pooled analysis, zinc-copper rhythmicity was disrupted in
ASD cases. In contrast to controls, in ASD cases, the cycle duration was
shorter (F = 52.25, P < 0.001), regularity was reduced (F = 47.99, P < 0.001), and complexity diminished (F = 57.30, P
< 0.001). With two distinct classification models that used metal
rhythmicity data, we achieved 90% accuracy in classifying cases and
controls, with sensitivity to ASD diagnosis ranging from 85 to 100% and
specificity ranging from 90 to 100%. These findings suggest that altered
zinc-copper rhythmicity precedes the emergence of ASD, and quantitative
biochemical measures of metal rhythmicity distinguish ASD cases from
controls.
Original language | English |
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Article number | eaat1293 |
Number of pages | 9 |
Journal | Science Advances |
Volume | 4 |
Issue number | 5 |
DOIs | |
Publication status | Published - 30 May 2018 |
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Dive into the research topics of 'Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder'. Together they form a unique fingerprint.Projects
- 1 Finished
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NIHR BRC Mental Health
Gunnell, D. J. (Principal Investigator)
1/04/17 → 31/03/22
Project: Research, Parent
Profiles
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Professor Dheeraj Rai
- Bristol Medical School (PHS) - Professor of Neurodevelopmental Psychiatry
- Migration Mobilities Bristol
- Bristol Population Health Science Institute
- Centre for Academic Mental Health
Person: Academic , Member