Autism, fever, epigenetics and the locus coeruleus

Mark F. Mehler, Dominick P. Purpura

Research output: Contribution to journalReview article

73 Scopus citations

Abstract

Some children with autism spectrum disorders (ASD) exhibit improved behaviors and enhanced communication during febrile episodes. We hypothesize that febrigenesis and the behavioral-state changes associated with fever in autism depend upon selective normalization of key components of a functionally impaired locus coeruleus-noradrenergic (LC-NA) system. We posit that autistic behaviors result from developmental dysregulation of LC-NA system specification and neural network deployment and modulation linked to the core behavioral features of autism. Fever transiently restores the modulatory functions of the LC-NA system and ameliorates autistic behaviors. Fever-induced reversibility of autism suggests preserved functional integrity of widespread neural networks subserving the LC-NA system and specifically the subsystems involved in mediating the cognitive and behavioral repertoires compromised in ASD. Alterations of complex gene-environmental interactions and associated epigenetic mechanisms during seminal developmental critical periods are viewed as instrumental in LC-NA dysregulation as emphasized by the timing and severity of prenatal maternal stressors on autism prevalence. Our hypothesis has implications for a rational approach to further interrogate the interdisciplinary etiology of ASD and for designing novel biological detection systems and therapeutic agents that target the LC-NA system's diverse network of pre- and postsynaptic receptors, intracellular signaling pathways and dynamic epigenetic remodeling processes involved in their regulation and functional plasticity.

Original languageEnglish (US)
Pages (from-to)388-392
Number of pages5
JournalBrain Research Reviews
Volume59
Issue number2
DOIs
StatePublished - Mar 1 2009

Keywords

  • Developmental critical period
  • Gene-environmental interaction
  • Homeostatic signal
  • Imprinted gene
  • Neuromodulator
  • Pharmacoepigenomic agent
  • Prenatal stressor
  • Sensorimotor processing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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