Autism spectrum conditions have been hypothesized to be an exaggeration of normal male low-empathizing and high-systemizing behaviors. We tested this hypothesis at the molecular level by performing comprehensive multi-analyte profiling of blood serum from adult subjects with Asperger's syndrome (AS) compared with controls. This led to identification of distinct sex-specific biomarker fingerprints for male and female subjects. Males with AS showed altered levels of 24 biomarkers including increased levels of cytokines and other inflammatory molecules. Multivariate statistical classification of males using this panel of 24 biomarkers revealed a marked separation between AS and controls with a sensitivity of 0.86 and specificity of 0.88. Testing this same panel in females did not result in a separation between the AS and control groups. In contrast, AS females showed altered levels of 17 biomarkers including growth factors and hormones such as androgens, growth hormone and insulin-related molecules. Classification of females using this biomarker panel resulted in a separation between AS and controls with sensitivities and specificities of 0.96 and 0.83, respectively, and testing this same panel in the male group did not result in a separation between the AS and control groups. The finding of elevated testosterone in AS females confirmed predictions from the ‘extreme male brain’ and androgen theories of autism spectrum conditions. We conclude that to understand the etiology and development of autism spectrum conditions, stratification by sex is essential.
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This work was funded by the Stanley Medical Research Institute, Psynova Neurotech and the Three Guineas Project Grant, Cambridge Lifespan Asperger Syndrome Service. Insulin-related assays were performed by Keith Burling at the NIHR Cambridge Biomedical Research Centre, Core Biochemistry Assay Laboratory, Addenbrookes Hospital, Cambridge, UK.
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
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Schwarz, E., Guest, P., Rahmoune, H. et al. Sex-specific serum biomarker patterns in adults with Asperger's syndrome. Mol Psychiatry 16, 1213–1220 (2011). https://doi.org/10.1038/mp.2010.102
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