title: Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.
abstract: Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.
authors.affiliation: 1] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands [3] Department 'Nieuwe Kennis', Delta Center for Mental Health Care, Rotterdam, The Netherlands.
authors.forename: N J M
authors.initials: NJ
authors.lastname: van Beveren
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: E
authors.initials: E
authors.lastname: Schwarz
authors.affiliation: Department of Psychology, DeSales University, Center Valley, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Noll
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Meijer
authors.affiliation: Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Haan
authors.affiliation: 1] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood; D058068:Endophenotypes / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D011384:Proinsulin / Q000097:blood; D012016:Reference Values; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D002096:C-Peptide; D018836:Inflammation Mediators; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D019382:Human Growth Hormone; D011384:Proinsulin