Protein biomarkers may be the key to schizophrenia diagnosis
Date: 16.8.2006
Schizophrenia is a surprisingly common disease, affecting about 1% of the world's population. The common perception of schizophrenic patients is that they suffer from dual (or split) personality but the situation is far more complex, with several known types such as catatonic, paranoid and disorganised schizophrenia. Diagnosing the disease can be complicated by the patient's behaviour but it is generally confirmed by a combination of symptoms.
The so-called positive symptoms such as hallucinations, delusions and disordered thinking are complemented by negative symptoms like apathy and the inability to express emotion, which could be mistaken for depression or laziness. The third category, cognitive symptoms, includes problems with working memory and the inability to uphold attention.
There is a strong genetic link in the disease, with people more likely to develop it if they have immediate relatives with a history of schizophrenia or other particular psychiatric disorders such as bipolar disorder. The people at greatest risk are the second identical twin if the first is a sufferer, but even people with a first degree relative (parent, brother or sister) have a 10% chance of succumbing to the disease.
Now, proteomics might be able to provide a biochemical basis for diagnosing schizophrenia. Changes in the amounts of certain proteins in schizophrenic patients compared with control subjects might lead to the identification of one or more proteins that could be used as biomarkers. Recent research has linked the pathophysiology of the disease with changes in the regulation of the inflammatory response. The cytokine proteins group have been implicated and these may have various inflammatory effects within the central nervous system that impact upon schizophrenia.
So researchers have undertaken a proteomics study of the plasma from 22 male schizophrenic patients undergoing therapeutic treatment with clozapine and compared the results with those from a group of 20 healthy male controls. Lin He from the Bio-X Center at Shanghai Jiao Tong University and Chinese colleagues subjected the samples to two-dimensional gel electrophoresis, with isoelectric focusing at pH 3-7 followed by SDS-PAGE.
Following gel staining with Coomassie blue G-250, approximately 1500 protein spots were detected by the imaging software and 66 clear spots were selected for further analysis. They were identified by peptide mass fingerprinting after digestion with trypsin and matrix-assisted laser desorption/ionisation mass spectrometry of the subsequent peptide mixtures. The 66 spots corresponded to 28 individual proteins, with most of the proteins having multiple spots corresponding to different forms.
When the control and patient protein levels were compared, it was evident that seven proteins were present at significantly different abundances between the two cases. The acute phase proteins haptoglobin alpha2 chain, haptoglobin beta chain, alpha1-antitrypsin and complement factor B precursor were all up-regulated in schizophrenia patients.
Conversely, apolipoprotein A-I (apoA-I) and transthyretin (TTR) were both down-regulated in patients. A portion of TTR is carried in plasma by binding to apoA-I, so the researchers suggested that this interaction might be relevant to the pathogenesis of schizophrenia and this will be an area of future research for the team. The seventh differentially regulated protein was apolipoprotein A-IV, which was more abundant in patients.
The team reflected on one limitation of their study, which is the estimation of protein abundances in 2D gels when different isoforms of a given protein have different electrophoretic mobilities. This makes it very difficult to quantify one protein accurately, with the possibility of some isoforms being omitted. Nonetheless, the abundances of haptoglobin alpha2 chain and haptoglobin beta chain were approximately two-fold higher than in controls, so they can be regarded with confidence as potential biomarkers of schizophrenia.
However, acute phase proteins are known to be non-specific markers of immune system changes due, perhaps, to infection, stress or inflammation, so they must be used as biomarkers only in conjunction with other indicators of schizophrenia.
"Source":[ http://www.separationsnow.com/coi/cda/detail.cda?id=13785&type=Feature&chId=6&page=1]
