title: Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia.
abstract: The molecular basis of schizophrenia is poorly understood; however, different brain regions are believed to play distinct roles in disease symptomology. We have studied gene expression in the superior temporal cortex (Brodmann area 22; BA22), which may play a role in positive pathophysiology, and compared our results with data from the anterior prefrontal cortex (BA10), which shows evidence for a role in negative symptoms. Genome-wide mRNA expression was determined in the BA22 region in 23 schizophrenics and 19 controls and compared with a BA10 data set from the same subjects. After adjustments for confounding sources of variation, we carried out GeneGO pathway enrichment analysis in each region. Significant differences were seen in age-related transcriptional changes between the BA22 and the BA10 regions, 21.8% and 41.4% of disease-associated transcripts showing age association, respectively. After removing age associated changes from our data, we saw the highest enrichment in processes mediating cell adhesion, synaptic contact, cytoskeletal remodelling, and apoptosis in the BA22 region. For the BA10 region, we observed the strongest changes in reproductive signalling, tissue remodelling, and cell differentiation. Further exploratory analysis also identified potentially disease-relevant processes that were undetected in our more stringent primary analysis, including autophagy in the BA22 region and the amyloid process in the BA10 region. Collectively, our analysis suggests disruption of many common pathways and processes underpinning synaptic plasticity in both regions in schizophrenia, whereas individual regions emphasize changes in certain pathways that may help to highlight pathway-specific therapeutic opportunities to treat negative or positive symptoms of the disease.
authors.affiliation: Computational Biology, Quantitative Sciences, Biopharmaceuticals, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barnes
authors.forename: Julie
authors.initials: J
authors.lastname: Huxley-Jones
authors.forename: Peter R
authors.initials: PR
authors.lastname: Maycox
authors.forename: Mark
authors.initials: M
authors.lastname: Lennon
authors.forename: Amy
authors.initials: A
authors.lastname: Thornber
authors.forename: Fiona
authors.initials: F
authors.lastname: Kelly
authors.forename: Stewart
authors.initials: S
authors.lastname: Bates
authors.forename: Adam
authors.initials: A
authors.lastname: Taylor
authors.forename: Juliet
authors.initials: J
authors.lastname: Reid
authors.forename: Neil
authors.initials: N
authors.lastname: Jones
authors.forename: Jörn
authors.initials: J
authors.lastname: Schroeder
authors.forename: Carol A
authors.initials: CA
authors.lastname: Scorer
authors.forename: Ceri
authors.initials: C
authors.lastname: Davies
authors.forename: Jim J
authors.initials: JJ
authors.lastname: Hagan
authors.forename: James N C
authors.initials: JN
authors.lastname: Kew
authors.forename: Claire
authors.initials: C
authors.lastname: Angelinetta
authors.forename: Tariq
authors.initials: T
authors.lastname: Akbar
authors.forename: Steven
authors.initials: S
authors.lastname: Hirsch
authors.forename: Ann M
authors.initials: AM
authors.lastname: Mortimer
authors.forename: Thomas R E
authors.initials: TR
authors.lastname: Barnes
authors.forename: Jackie
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger