Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia.
The aim of this study was to analyze gene expression in blood of patients with newly-diagnosed schizophrenia during their first psychotic episode and subsequent remission. Whole blood samples were obtained from 32 untreated patients presenting with their first psychotic episode suggestive of schizophrenia and 32 age- and gender-matched controls. Using Affymetrix micoarrays, we identified significantly altered expression of 180 gene probes in psychotic patients compared to controls. A subset of four significantly changed genes was further confirmed with QRT-PCR. The following genes were significantly altered in patients: glucose transporter, SLC2A3 (p<0.001) and actin assembly factor DAAM2 (p<0.001) were increased, whereas translation, zinc metallopeptidase, neurolysin 1 and myosin C were significantly decreased (p<0.05). Expression of these candidate markers was also analyzed in a longitudinal study (12-24 months) in 12 patients who achieved full remission. Interestingly, expression of DAAM2 returned to control levels in patients who were in remission after their first psychotic episode, suggesting that its expression correlates with diseases progression and/or response to treatment. In summary, we identified changes of gene expression from peripheral blood which might help discriminate patients with schizophrenia from controls. While these results are promising, especially for DAAM2 whose polymorphic variants have been found significantly associated with schizophrenia, it will be important to analyze larger cohorts of patients in order to firmly establish changes in gene expression as blood markers of schizophrenia.
Department of Psychiatry, Zagreb University Hospital Centre and Zagreb School of Medicine, Zagreb, Croatia. mrojnic@gmail.com
Martina Rojnic
MR
Kuzman
Vesna
V
Medved
Janos
J
Terzic
Dimitri
D
Krainc
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D043423:Carboxypeptidase H / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D055106:Genome-Wide Association Study; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins; D025102:Myosin Type III / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult; D020741:rho GTP-Binding Proteins
D014150:Antipsychotic Agents; D015415:Biomarkers; C478654:DAAM2 protein, human; D051246:Glucose Transport Proteins, Facilitative; D051274:Glucose Transporter Type 3; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C495687:SLC2A3 protein, human; D043423:Carboxypeptidase H; D008666:Metalloendopeptidases; C062316:neurolysin; D025102:Myosin Type III; D020741:rho GTP-Binding Proteins