Peripheral biomarkers in schizophrenia: A meta-analysis of microarray gene-expression datasets.

Background: Schizophrenia (SCZ) is a severe psychiatric disorder with a complex pathophysiology. Given its prevalence, high risk of mortality, early onset, and high levels of disability, researchers have attempted to develop early detection strategies for facilitating timely pharmacological and/or non-pharmacological interventions. Here, we performed a meta-analysis of publicly available gene expression datasets in peripheral tissues in SCZ and healthy controls (HC) to detect consistent patterns of illness-associated gene expression. We also tested whether our earlier finding of a down-regulation of NPTX2 expression in the brain of SCZ patients replicated in peripheral tissues.

Methods: We conducted a systematic search in the GEO repository (https://www.ncbi.nlm.nih.gov/gds/), and identified 3 datasets matching our inclusion criteria: GSE62333, GSE18312 and GSE27383. After quality controls, the total sample size was: SCZ = 71 and HC = 57 (SCZ range: n = 12 - 40; HC range: n = 8 - 29).

Results: The results of the meta-analysis conducted with the GeneMeta package revealed 2 genes with FDR < 0.05: atlastin GTPase 3 (ATL3) (up-regulated) and arachidonate 15-lipoxygenase, type B (ALOX15B) (down-regulated). The result for ATL3 was confirmed using the Weighted Z-test method, whereas we found a suggestive signal for ALOX15B (FDR < 0.10).

Conclusions : hese data point to alterations of peripheral expression of ATL3 in SCZ, but did not confirm the significant association signal found for NPTX2 in post-mortem brain samples. These findings await replication in newly recruited SCZ samples as well as complementary analysis of their encoded peptides in blood.