Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects

Abstract

Objectives. To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. Methods. Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS^E), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. Results. This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic–pituitary–adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. Conclusions. Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.

Key words::

• Schizophrenia
• biochemical markers
• psychopathology
• neuropsychiatry
• ACTH

Acknowledgements

This work was supported by funding from the Stanley Medical Research Institute (SMRI) and the European Union FP7 SchizDX research programme (grant reference 223427). We also thank the SMRI for the generous donation of post-mortem pituitaries and Maree Webster for useful discussion. The funding sources had no further role in: the study design; in the collection, analysis and interpretation of the data; in the report writing; and in the decision to submit the paper for publication.

Statement of Interest

None to declare.