The possible interplay of synaptic and clock genes in autism spectrum disorders

Cold Spring Harb Symp Quant Biol. 2007:72:645-54. doi: 10.1101/sqb.2007.72.020.


Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by deficits in social communication, absence or delay in language, and stereotyped and repetitive behaviors. Results from genetic studies reveal one pathway associated with susceptibility to ASD, which includes the synaptic cell adhesion molecules NLGN3, NLGN4, and NRXN1 and a postsynaptic scaffolding protein SHANK3. This protein complex is crucial for the maintenance of functional synapses as well as the adequate balance between neuronal excitation and inhibition. Among the factors that could modulate this pathway are the genes controlling circadian rhythms. Indeed, sleep disorders and low melatonin levels are frequently observed in ASD. In this context, an alteration of both this synaptic pathway and the setting of the clock would greatly increase the risk of ASD. In this chapter, I report genetic and neurobiological findings that highlight the major role of synaptic and clock genes in the susceptibility to ASD. On the basis of these lines of evidence, I propose that future studies of ASD should investigate the circadian modulation of synaptic function as a focus for functional analyses and the development of new therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autistic Disorder / complications
  • Autistic Disorder / drug therapy
  • Autistic Disorder / genetics*
  • Autistic Disorder / physiopathology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cell Adhesion Molecules, Neuronal
  • Child
  • Circadian Rhythm / genetics*
  • Circadian Rhythm / physiology
  • Female
  • Humans
  • Male
  • Melatonin / therapeutic use
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Models, Genetic
  • Models, Neurological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / physiology
  • Sleep Wake Disorders / complications
  • Sleep Wake Disorders / genetics
  • Sleep Wake Disorders / physiopathology
  • Synapses / genetics*
  • Synapses / physiology


  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Membrane Proteins
  • NLGN4X protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • SHANK3 protein, human
  • neuroligin 3
  • Melatonin