title: Targeted multiplexed selected reaction monitoring analysis evaluates protein expression changes of molecular risk factors for major psychiatric disorders.
abstract: BACKGROUND
  Extensive research efforts have generated genomic, transcriptomic, proteomic, and functional data hoping to elucidate psychiatric pathophysiology. Selected reaction monitoring, a recently developed targeted proteomic mass spectrometric approach, has made it possible to evaluate previous findings and hypotheses with high sensitivity, reproducibility, and quantitative accuracy.
  
  
  METHODS
  Here, we have developed a labelled multiplexed selected reaction monitoring assay, comprising 56 proteins previously implicated in the aetiology of major psychiatric disorders, including cell type markers or targets and effectors of known psychopharmacological interventions. We analyzed postmortem anterior prefrontal cortex (Brodmann area 10) tissue of patients diagnosed with schizophrenia (n=22), bipolar disorder (n=23), and major depressive disorder with (n=11) and without (n=11) psychotic features compared with healthy controls (n=22).
  
  
  RESULTS
  Results agreed with several previous studies, with the finding of alterations of Wnt-signalling and glutamate receptor abundance predominately in bipolar disorder and abnormalities in energy metabolism across the neuropsychiatric disease spectrum. Calcium signalling was predominantly affected in schizophrenia and affective psychosis. Interestingly, we were able to show a decrease of all 4 tested oligodendrocyte specific proteins (MOG, MBP, MYPR, CNPase) in bipolar disorder and to a lesser extent in schizophrenia and affective psychosis. Finally, we provide new evidence linking ankyrin 3 specifically to affective psychosis and the 22q11.2 deletion syndrome-associated protein septin 5 to schizophrenia.
  
  
  CONCLUSIONS
  Our study highlights the potential of selected reaction monitoring to evaluate the protein abundance levels of candidate markers of neuropsychiatric spectrum disorders, providing a high throughput multiplex platform for validation of putative disease markers and drug targets.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom (Wesseling, Gottschalk, and Bahn); Department of Neuroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (Dr Bahn).H.W. and M.G.G. contributed equally to this work.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Wesseling
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom (Wesseling, Gottschalk, and Bahn); Department of Neuroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (Dr Bahn).H.W. and M.G.G. contributed equally to this work.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Gottschalk
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom (Wesseling, Gottschalk, and Bahn); Department of Neuroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands (Dr Bahn).H.W. and M.G.G. contributed equally to this work. sb209@cam.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D017397:Prefrontal Cortex / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism*
keywords: CamKII; GSK3b; SRMstats; microglia.; myelination