Type

Journal Article

Authors

D R Cotter
G Cagney
K Wynne
E Brindley
A Wolff
P Dicker
J A English
L M Lopez
M Föcking

Subjects

Psychiatry

Topics
genome wide association schizophrenia n methyl d aspartate anterior cingulate cortex medical research calcium signaling long term potentiation density

Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. (2014)

Abstract 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<0.0015). Pathway analysis of the differentially expressed proteins implicated the cellular processes of endocytosis, long-term potentiation and calcium signaling. Both single-gene and gene-set enrichment analyses in genome-wide association data from the largest schizophrenia sample to date of 13 689 cases and 18 226 controls show significant association of HIST1H1E and MAPK3, and enrichment of our PSD proteome. Taken together, our data provide robust evidence implicating PSD-associated proteins and genes in schizophrenia, and suggest that within the PSD, NMDA-interacting and endocytosis-related proteins contribute to disease pathophysiology.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

D R Cotter, G Cagney, K Wynne, E Brindley, A Wolff, P Dicker, J A English, L M Lopez, M Föcking

Experts in our system

1
David R Cotter
Royal College of Surgeons in Ireland
Total Publications: 56
 
2
Gerard Cagney
Royal College of Surgeons in Ireland
Total Publications: 54
 
3
Kieran Wynne
Royal College of Surgeons in Ireland
Total Publications: 45
 
4
Patrick Dicker
Royal College of Surgeons in Ireland
Total Publications: 95
 
5
Jane A English
Royal College of Surgeons in Ireland
Total Publications: 24
 
6
Lorna Lopez
Royal College of Surgeons in Ireland
Total Publications: 17
 
7
Melanie Föcking
Royal College of Surgeons in Ireland
Total Publications: 20