Schizophrenia: from developmental deviance to dopamine dysregulation.
Two major theories of schizophrenia are respectively, the neurodevelopmental hypothesis and the dopamine hypothesis. Each of these has recently been revised. Firstly, the classical neurodevelopmental hypothesis has been modified to include the pathogenic effects of psychostimulants and cannabis abuse, and also of chronic social adversity; it is perhaps now more appropriately termed, the developmental hypothesis. Secondly, recent amendments to the dopamine hypothesis suggest that excess striatal dopamine is responsible for increased salience being given to insignificant events and thoughts, and that this underpins the development of psychotic symptoms. Traditionally, it has been thought that this striatal dopamine dysregulation might be secondary to frontal dysfunction. However, recent animal research shows that over-expression of striatal D(2) receptors results in frontal dysfunction manifesting as cognitive difficulties and animal equivalents of so-called negative symptoms. This raises the question whether early intervention may prevent the development of these latter problems. Finally, the two theories are beginning to be integrated through the growing evidence that all the developmental risk factors which increase risk of schizophrenia appear to act by facilitating dopamine dysregulation.
Murray
Robin M
RM
Institute of Psychiatry, De Crespigny Park, London, United Kingdom. robin.murray@iop.kcl.ac.uk
Lappin
Julia
J
Di Forti
Marta
M
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D012559:Schizophrenia / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012565:Schizophrenic Psychology; D012919:Social Behavior
D004298:Dopamine