The synapse in schizophrenia.
It has been several decades since synaptic dysfunction was first suggested to play a role in schizophrenia, but only in the last few years has convincing evidence been obtained as progress has been made in elucidating the genetic underpinnings of the disorder. In the intervening years much has been learned concerning the complex macromolecular structure of the synapse itself, and genetic studies are now beginning to draw upon these advances. Here we outline our current understanding of the genetic architecture of schizophrenia and examine the evidence for synaptic involvement. A strong case can now be made that disruption of glutamatergic signalling pathways regulating synaptic plasticity contributes to the aetiology of schizophrenia.
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cathays, Cardiff, CF24 4HQ, UK.
Andrew J
AJ
Pocklington
Michael
M
O'Donovan
Michael J
MJ
Owen
D000818:Animals; D056915:DNA Copy Number Variations; D006801:Humans; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission
proteomics; psychiatric genetics; synaptic plasticity