Does subtle disturbance of neuronal migration contribute to schizophrenia and other neurodevelopmental disorders? Potential genetic mechanisms with possible treatment implications.
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.
Deutsch
Stephen I
SI
Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA, USA. deutscsi@evms.edu
Burket
Jessica A
JA
Katz
Elionora
E
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D006801:Humans; D054082:Lissencephaly / Q000235:genetics / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D012697:Serine Endopeptidases / Q000235:genetics
D015816:Cell Adhesion Molecules, Neuronal; C412476:DISC1 protein, human; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases