Distinct proteomic profiles in post-mortem pituitary glands from bipolar disorder and major depressive disorder patients. (January 2015)

• Record Type: Journal Article
• Authors: Stelzhammer, Viktoria; Alsaif, Murtada; Chan, Man K.; Rahmoune, Hassan; Steeb, Hannah; Guest, Paul C.; Bahn, Sabine
• Is Part Of: Journal of psychiatric research. Volume 60(2015:Jan.)
• Page Start: 40
• Page End: 48
• Publication Date: 2015-01
• Subjects: Bipolar disorder -- Major depressive disorder -- HPA-axis -- Pituitary -- Mass spectrometry; Psychiatry -- Periodicals; Mental Disorders -- Periodicals; Maladies mentales -- Périodiques; Psychiatry; Electronic journals; Periodicals; 616.89005
• DOI: 10.1016/j.jpsychires.2014.09.022
• Languages: English
• ISSNs: 0022-3956

Abstract

Abstract: Disturbances of the hypothalamic–pituitary–adrenal axis have been implicated in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). To examine this further, we carried out proteomic profiling of post-mortem pituitaries from 13 BD and 14 MDD patients, in comparison to 15 controls. Liquid chromatography–mass spectrometry (LC–MS E ) analysis showed that BD patients had significantly increased levels of the major pituitary hormones pro-opiomelanocortin (POMC) and galanin. BD patients also showed changes in proteins associated with gene transcription, stress response, lipid metabolism and growth signalling. In contrast, LC–MS E profiling revealed that MDD patients had significantly decreased levels of the prohormone-converting enzyme carboxypeptidease E and follow-up enzymatic analysis showed decreased activity of prolyl-oligopeptidase convertase. This suggested that altered prohormone processing may occur in pituitaries of MDD patients. In addition, MDD patients had significant changes in proteins involved in intracellular transport and cytoskeletal signalling. Finally, we carried out selective reaction monitoring (SRM) mass spectrometry profiling for validation of protein changes in key biological pathways. This confirmed increased POMC levels in BD patients with no change in the levels of this prohormone in MDD. This study demonstrates that proteomic profiling analysis of the pituitary can lead to new insights into the pathophysiology of BD and MDD. Also, given that the pituitary directly releases a variety of bioactive molecules into the bloodstream, many of the proteins identified here could serve as focal points in the search for peripheral biomarkers in clinical or drug treatment studies of BD and MDD patients. Highlights: Pituitary disturbances have been implicated in psychiatric disorders. This proteomic study identified differences in pituitaries from BD and MDD patients. BD patients had changes mainly in hormones, growth factors and metabolism. MDD patients had changes in prohormone converting enzymes and cell structure proteins. Many of these proteins could be focal points in the search for peripheral biomarkers.