Increased α-Defensins as a Blood Marker for Schizophrenia Susceptibility

• Published in: Molecular & cellular proteomics Vol. 7; no. 7; p. 1204
• Main Authors: Rachel M. Craddock, Jeffrey T. Huang, Edmund Jackson, Nathan Harris, E. Fuller Torrey, Marlis Herberth, Sabine Bahn
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 01-07-2008
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M700459-MCP200

Schizophrenia is a severe psychotic illness affecting 1% of the general population. There are no consistent pathological features,
and the disorder is defined by a complex symptomatology, which overlaps with other psychiatric illnesses. Diagnosis is based
on a clinical interview, relying on the patient meeting criteria according to diagnosis manuals, including Diagnostic and Statistical Manual of Mental Disorders , 4th Ed. and International Statistical Classification of Diseases , 10th Revision. Because of the ambiguous symptoms, the diagnostic process can take many months and often years. Rapid and
effective treatment has been shown to impact positively on disease progression and outcome, and it is therefore important
to identify disease-associated biomarkers allowing early diagnosis. Reliable biomarkers can be used for the development of
diagnostic tests and may also help us understand the underlying pathology of this disorder. In the present study, proteins
from anti-CD3 stimulated and unstimulated peripheral blood T cell lysates from 15 minimally medicated and unmedicated patients
and 15 age-, sex-, race-, and smoking-matched controls were profiled on cation exchange (CM10) chips using SELDI-TOF. Partial
least squares discriminate analysis was used to separate patient and control groups according to the expression of 108 detected
peaks, and two peaks of 3,374 and 3,450 Da, corresponding to α-defensins based on masses and cationic properties, were found
to contribute significantly to the separation of patient and control groups. Reduction of T cell lysates with DTT resulted
in a 6-Da shift in the mass of these peaks consistent with the presence of three cysteine bonds in the structure, confirming
them as α-defensins. Quantification of α-defensins in T cell lysates from six patients and 18 healthy controls was carried
out by ELISA, which also showed that α-defensin levels were significantly increased in patient lysates when compared with
matched controls ( p = 0.0197). Plasma from 21 monozygotic twins discordant for schizophrenia and eight healthy unaffected twin pairs was also
analyzed for the expression of α-defensins by ELISA. Notably both affected and unaffected twins were found to have significantly
elevated α-defensin levels compared with healthy control twin pairs ( p = 0.0014 and p = 0.0115, respectively). Increased expression of α-defensins in unaffected as well as affected discordant monozygotic twins
is of particular interest as monozygotic twins share genes and usually environmental upbringing. The unaffected twin therefore
represents the biological and environmental risk of developing schizophrenia in the absence of overt symptomatology and therapeutic
medication. These findings suggest that α-defensins could be an important early indicator of the risk of schizophrenia.