title: Changes in winter depression phenotype correlate with white blood cell gene expression profiles: a combined metagene and gene ontology approach.
abstract: In the present study we evaluate the feasibility of gene expression in white blood cells as a peripheral marker for winter depression. Sixteen patients with winter type seasonal affective disorder were included in the study. Blood was taken by venous puncture at three time points; in winter prior and following bright light therapy and in summer. RNA was isolated, converted into cRNA, amplified and hybridized on Illumina® gene expression arrays. The raw optical array data were quantile normalized and thereafter analyzed using a metagene approach, based on previously published Affymetrix gene array data. The raw data were also subjected to a secondary analysis focusing on circadian genes and genes involved in serotonergic neurotransmission. Differences between the conditions were analyzed, using analysis of variance on the principal components of the metagene score matrix. After correction for multiple testing no statistically significant differences were found. Another approach uses the correlation between metagene factor weights and the actual expression values, averaged over conditions. When comparing the correlations of winter vs. summer and bright light therapy vs. summer significant changes for several metagenes were found. Subsequent gene ontology analyses (DAVID and GeneTrail) of 5 major metagenes suggest an interaction between brain and white blood cells. The hypothesis driven analysis with a smaller group of genes failed to demonstrate any significant effects. The results from the combined metagene and gene ontology analyses support the idea of communication between brain and white blood cells. Future studies will need a much larger sample size to obtain information at the level of single genes.
authors.affiliation: University of Groningen, University Medical Centre Groningen, University Centre for Psychiatry, the Netherlands. Electronic address: f.j.bosker@umcg.nl.
authors.forename: Fokko J
authors.initials: FJ
authors.lastname: Bosker
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Epidemiology, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Terpstra
authors.affiliation: University of Groningen, University Medical Centre Groningen, University Centre for Psychiatry, the Netherlands.
authors.forename: Anatoliy V
authors.initials: AV
authors.lastname: Gladkevich
authors.affiliation: University of Groningen, University Medical Centre Groningen, Laboratory Medicine, the Netherlands.
authors.forename: D A
authors.initials: DA
authors.lastname: Janneke Dijck-Brouwer
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, the Netherlands; Baylor College of Medicine, One Baylor Plaza, Houston, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: te Meerman
authors.affiliation: University of Groningen, University Medical Centre Groningen, University Centre for Psychiatry, the Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: University of Groningen, University Medical Centre Groningen, University Centre for Psychiatry, the Netherlands.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schoevers
authors.affiliation: University of Groningen, University Medical Centre Groningen, University Centre for Psychiatry, the Netherlands.
authors.forename: Ybe
authors.initials: Y
authors.lastname: Meesters
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D010641:Phenotype; D010789:Phototherapy; D011569:Psychiatric Status Rating Scales; D016574:Seasonal Affective Disorder / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D012621:Seasons; D055815:Young Adult
keywords: Bright-light therapy; Gene ontology analysis; Metagene analysis; Peripheral gene expression; Winter depression