The stanley neuropathology consortium integrative database: a novel, web-based tool for exploring neuropathological markers in psychiatric disorders and the biological processes associated with abnormalities of those markers

Abstract

An integrative database, Stanley Neuropathology Consortium Integrative Database (SNCID) (http://sncid.stanleyresearch.org), has been developed to facilitate psychiatric research. The SNCID includes 1749 neuropathological markers measured in 12 different brain regions in 60 human subjects (15 each schizophrenia, bipolar disorder, depression, and unaffected controls). Genome-wide expression microarray datasets from three independent studies are also included. Statistical analysis tools such as variance analysis, correlation analysis, and functional annotation tools have been integrated into the database. In this report, we first replicate an earlier correlation analysis between genome-wide expression profiles and an abnormal cytoarchitectural marker using the SNCID. We then show the potential for identifying neuropathological markers that are abnormal in subjects with psychiatric disorders. We also identify biological pathways associated with several abnormal neuropathological markers, including those in the dopamine, glutamate, Reelin, and gamma-aminobutyric acid (GABA)ergic systems. Data exploration using the SNCID may provide insights into the biological pathways associated with the neurotransmitter abnormalities identified in subjects with major psychiatric disorders.

Figure 1

Data distribution and variance analysis for the number of perineuronal oligodendrocytes in the frontal cortex. Basic descriptive statistics and histogram for the marker (a). Box plots represent the median and distribution of the marker for each diagnostic group (b) for suicide vs non-suicide (c) and for psychotic features vs non-psychotic features (d).

Figure 2

The total number of probe sets correlated with the number of perineuronal oligodendrocytes and the significantly associated biological processes. (a) Screen shot captures the number of probe sets correlated with the perineuronal oligodendrocytes by p-values from genome-wide correlation analysis and (b) biological processes (gene ontology, all levels) overrepresented in the probe sets (n=243) significantly correlated with the marker (p<0.001). The functional annotation was done using an interface in the SNCID that links the SNCID (http://sncid.stanleyresearch.org) and DAVID (http://david.abcc.ncifcrf.gov/).

Figure 3

Biological processes (gene ontology, all levels) overrepresented in the probe sets significantly correlated with GAD₆₇ (a) and GAD₆₅ protein levels (b) in the frontal cortex. The functional annotation was done using an interface in the SNCID that links the SNCID (http://sncid.stanleyresearch.org) and DAVID (http://david.abcc.ncifcrf.gov/).