Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia.
The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders, and schizophrenia specifically. We enriched for this anatomical structure, in the anterior cingulate cortex, of 20 schizophrenia samples and 20 controls from the Stanley Medical Research Institute, and used unbiased shotgun proteomics incorporating label-free quantitation to identify differentially expressed proteins. Quantitative investigation of the PSD revealed more than 700 protein identifications and 143 differentially expressed proteins. Prominent among these were altered expression of proteins involved in clathrin-mediated endocytosis (CME) (Dynamin-1, adaptor protein 2) and N-methyl-D-aspartate (NMDA)-interacting proteins such as CYFIP2, SYNPO, SHANK3, ESYT and MAPK3 (all P
Post-mortem brains were donated by the Stanley Foundation Brain Bank Consortium courtesy of Llewellyn B Bigelow, Maree J Webster and staff. We thank the donors,Daire Quinn, Sinead Kinsella, Alison Gordon and Magdalena Hryniewiecka, for help with western blotting and animal work; Andrew Pocklington and George Kirov for the PSD gene lists, and Aniket Misra, Stuart MacGregor and Dave Hill for help with the gene-based analysis. We thank the Psychiatric Genetics Consortium, DIAGRAM(DIAbetes Genetics Replication And Meta-analysis) Consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) for providing genome-wide association study data. Access to and use of mass spectrometry instrumentation and computing facilities at the Conway Institute is gratefully acknowledged. This work was supported by a Brain and Behavior Research Foundation Award (to MF), the SMRI and the Irish Health Research Board through a Health Research Award (to DC,GC and MF) and a Health Research Board Clinician Scientist Award (to DC).
CommentsThe original article is available at https://www.nature.com
Published CitationFöcking M, Lopez LM, English JA, Dicker P, Wolff A, Brindley E, Wynne K, Cagney G, Cotter DR. Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Molecular Psychiatry. 2015;20(4):424-32
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