Does subtle disturbance of neuronal migration contribute to schizophrenia and other neurodevelopmental disorders? Potential genetic mechanisms with possible treatment implications

Eur Neuropsychopharmacol. 2010 May;20(5):281-7. doi: 10.1016/j.euroneuro.2010.02.005. Epub 2010 Mar 5.

Abstract

Pathways associated with genes that regulate neuronal migration by influencing the function of microtubules in the developing fetal brain may be interfered with as part of the "first-hit" of schizophrenia. In the fully-developed brain, these same pathways that impact microtubule function mediate at least some aspects of experience-dependent plasticity, which may also be impaired in schizophrenia. Whereas severe presentations of "lissencephaly" are associated with mutations and deletions of DISC1, LIS1 and the gene for the very low-density lipoprotein receptor, genetic variations of these loci are good candidate schizophrenia genes. Importantly, in the fully-developed brain, there is a possibility that at least some of the consequences of these disturbed genetic pathways that adversely affect microtubule function may be "bypassed" or mitigated.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Movement / genetics*
  • Extracellular Matrix Proteins / genetics
  • Humans
  • Lissencephaly / genetics
  • Lissencephaly / physiopathology
  • Microtubule-Associated Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Neurons / physiology*
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*
  • Serine Endopeptidases / genetics

Substances

  • Cell Adhesion Molecules, Neuronal
  • DISC1 protein, human
  • Extracellular Matrix Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein