Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1.
Schizophrenia (SZ) is primarily an adult psychiatric disorder in which disturbances caused by susceptibility genes and environmental insults during early neurodevelopment initiate neurophysiological changes over a long time course, culminating in the onset of full-blown disease nearly two decades later. Aberrant postnatal brain maturation is an essential mechanism underlying the disease. Currently, symptoms of SZ are treated with anti-psychotic medications that have variable efficacy and severe side effects. There has been much interest in the prodromal phase and the possibility of preventing SZ by interfering with the aberrant postnatal brain maturation associated with this disorder. Thus, it is crucial to understand the mechanisms that underlie the long-term progression to full disease manifestation to identify the best targets and approaches towards this goal. We believe that studies of certain SZ genetic susceptibility factors with neurodevelopmental implications will be key tools in this task. Accumulating evidence suggests that neuregulin-1 (NRG1) and disrupted-in-schizophrenia-1 (DISC1) are probably functionally convergent and play key roles in brain development. We provide an update on the role of these emerging concepts in understanding the complex time course of SZ from early neurodevelopmental disturbances to later onset and suggest ways of testing these in the future.
Jaaro-Peled
Hanna
H
Department of Psychiatry and Behavioral Neurosciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hayashi-Takagi
Akiko
A
Seshadri
Saurav
S
Kamiya
Atsushi
A
Brandon
Nicholas J
NJ
Sawa
Akira
A
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020890:Neuregulin-1 / Q000378:metabolism*; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology*
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4