Cognitive deficits are increasingly recognised as core features of schizophrenia, and it has long been known that antagonism of NMDA receptors at glutamatergic synapses can induce a schizophrenia-like psychosis that includes some of those deficits.42 This has led to a glutamate hypofunction hypothesis of schizophrenia. Glutamate receptors form multiprotein complexes with large sets of scaffold and signalling proteins including MAGUKs43 that are embedded in the PSD. It is clear that disruption of a number of synaptic proteins linked to glutamate receptor signalling alters cognitive function in rodents.44 The composition of the PSD has recently been identified in humans by some of the present authors,34 affording us an unprecedented opportunity to investigate the role of this complex in schizophrenia. Specifically, we tested the hypothesis that de novo CNVs in cases are enriched for genes encoding members of this complex.
