Gene expression meta-analysis reveals the up-regulation of CREB1 and CREBBP in Brodmann Area 10 of patients with schizophrenia.

ABSTRACT

Cognitive impairments characterize individuals with schizophrenia, and are correlated to the patients' functional outcome. The transcription factor Cyclic AMP-responsive element-binding protein-1 (CREB1) is involved in learning and memory processes. CREB1 and both CREB-binding protein (CREBBP) and E1A Binding Protein P300 (EP300), co-activators of CREB1, have been associated with schizophrenia. We performed a systematic meta-analysis of CREB1, CREBBP and EP300 differential expression in post mortem Brodmann Area 10 (BA10) samples of patients with schizophrenia vs. healthy controls, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two microarray datasets met the inclusion criteria (overall 41 schizophrenia samples and 38 controls were analyzed). We detect up-regulation of CREB1 and CREBBP in BA10 samples of patients with schizophrenia, while EP300 wasn't differentially expressed. The integration of two independent datasets and the positive correlation between the expression patterns of CREB1 and CREBBP increase the validity of the results. The up-regulation of CREB1 and its co-activator CREBBP might relate to BA10 altered activation that has been shown in schizophrenia. As BA10 was shown to be involved in the cognitive impairments associated with schizophrenia, this suggests involvement of CREB1 and CREBBP in the cognitive symptoms that characterize the disease.