Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

• Published in: Molecular psychiatry Vol. 15; no. 3; pp. 326 - 336
• Main Authors: Kim, S, Webster, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2010; Nature Publishing Group
• Subjects: Apoptosis; Autopsy; Behavioral Sciences; Biological Phenomena - genetics; Biological Psychology; Bipolar disorder; Bipolar Disorder - genetics; Bipolar Disorder - pathology; Brain architecture; Brain diseases; Brain research; Calbindin; Cell death; Central nervous system; Complications and side effects; Correlation analysis; Cortex (frontal); Cyclin-dependent kinases; Datasets; Depression - genetics; Depression - pathology; DNA microarrays; Gene expression; Gene Expression Profiling - methods; Genetic aspects; Genome-Wide Association Study - methods; Genomes; Health aspects; Humans; Independent study; Interneurons; Interneurons - metabolism; Interneurons - pathology; Kinases; Medical research; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Mental Disorders - genetics; Mental Disorders - pathology; Mental illness; Metadata; Molecular modelling; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurosciences; Oligodendrocytes; Oligodendroglia - metabolism; Oligodendroglia - pathology; Oligonucleotide Array Sequence Analysis - methods; original-article; Pharmacotherapy; Prefrontal cortex; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Proteins; Psychiatry; Research centers; Risk factors; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Statistical methods; Variables; Variance analysis; γ-Aminobutyric acid; United States; United States > US; correlation analysis; GABAergic neuron; microarray; oligodendrocyte
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2008.99

Cytoarchitectural abnormalities have been described in the prefrontal cortex of subjects with schizophrenia, bipolar disorder and depression. However, little is known about the gene expression profiles associated with these abnormalities. Genome-wide expression profiling technology provides an unbiased approach to identifying candidate genes and biological processes that may be associated with complex biological traits such as cytoarchitecture. In this study, we explored expression profiles associated with the abnormalities by using publicly available microarray metadata and cytoarchitectural data from post-mortem samples of the frontal cortex from 54 subjects (schizophrenia, n =14; bipolar disorder, n =13; depression, n =12 and controls n =15). Correlation analysis between genome-wide expression levels and cytoarchitectural traits revealed that 818 genes were significantly correlated with a decrease in the number of perineuronal oligodendrocytes across all subjects. A total of 600 genes were significantly correlated with a decrease in density of calbindin-positive interneurons across all subjects. Multiple biological processes including cellular metabolism, central nervous system development, cell motility and programmed cell death were significantly overrepresented in both correlated gene lists. These findings may provide novel insights into the molecular mechanisms that underlie the cytoarchitectural abnormalities of perineuronal oligodendrocytes and calbindin-containing GABAergic interneurons in the prefrontal cortex of the major psychiatric disorders.