Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders

Science. 2015 Nov 20;350(6263):10.1126/science.aab3897 aab3897. doi: 10.1126/science.aab3897. Epub 2015 Oct 15.

Abstract

Research in the genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. Although the exact identity of many of the genes remains to be discovered, genes identified to date encode proteins that play roles in certain conserved pathways: protein synthesis, transcriptional and epigenetic regulation, and synaptic signaling. The next generation of research in neurodevelopmental disorders must address the neural circuitry underlying the behavioral symptoms and comorbidities, the cell types playing critical roles in these circuits, and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we can leverage the heterogeneity of neurodevelopmental disorders into precision medicine will the mechanism-based therapeutics for these disorders start to unlock success.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Autistic Disorder / drug therapy
  • Autistic Disorder / genetics
  • Behavior
  • Brain / growth & development
  • Brain / metabolism
  • Chromatin Assembly and Disassembly
  • Clinical Trials as Topic
  • Epigenesis, Genetic
  • Genes
  • Genetic Predisposition to Disease*
  • Humans
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mutation
  • Neural Pathways / metabolism
  • Neurodevelopmental Disorders / drug therapy*
  • Neurodevelopmental Disorders / genetics*
  • Precision Medicine / methods*
  • Protein Biosynthesis / genetics
  • Transcription, Genetic
  • Translational Research, Biomedical