Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

Mol Psychiatry. 2015 Feb;20(1):118-25. doi: 10.1038/mp.2014.98. Epub 2014 Sep 9.

Abstract

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / genetics
  • Autistic Disorder / pathology*
  • Brain / pathology*
  • Disease Models, Animal*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Multigene Family / genetics*