1. ¹Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland
2. ²Proteome Research Centre, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
3. ³Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
4. ⁴Department of Molecular and Cellular Therapeutics, Royal College of Surgeons, Dublin, Ireland
5. ⁵School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
6. ⁶King's College, Section of Stress, Psychiatry and Immunology, Division of Psychological Medicine, Institute of Psychiatry, London, UK
7. ⁷Kennedy Institute of Rheumatology Division, Imperial College, London, UK

Correspondence: Professor DR Cotter, Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland. E-mail: drcotter@rcsi.ie

Received 22 February 2007; Revised 16 July 2007; Accepted 31 July 2007; Published online 16 October 2007.

Abstract

There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P<0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.