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Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression

Gaiteri, C and Guilloux, JP and Lewis, DA and Sibille, E (2010) Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression. PLoS ONE, 5 (4).

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Coordinated gene transcript levels across tissues (denoted "gene synchrony") reflect converging influences of genetic, biochemical and environmental factors; hence they are informative of the biological state of an individual. So could brain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies? Using bootstrapped Pearson correlation for transcript levels for the same genes across distinct brain areas, we report robust gene transcript synchrony between the amygdala and cingulate cortex in the human postmortem brain of normal control subjects (n = 14; Control/Permutated data, p<0.000001). Coordinated expression was confirmed across distinct prefrontal cortex areas in a separate cohort (n = 19 subjects) and affected different gene sets, potentially reflecting regional network- and function-dependent transcriptional programs. Genewise regional transcript coordination was independent of age-related changes and array technical parameters. Robust shifts in amygdala-cingulate gene synchrony were observed in subjects with major depressive disorder (MDD, denoted here "depression") (n = 14; MDD/Permutated data, p<0.000001), significantly affecting between 100 and 250 individual genes (10-30% false discovery rate). Biological networks and signal transduction pathways corresponding to the identified gene set suggested putative dysregulated functions for several hormone-type factors previously implicated in depression (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids; p<0.01 for association with depression-related networks). In summary, we showed that coordinated gene expression across brain areas may represent a novel molecular probe for brain structure/function that is sensitive to disease condition, suggesting the presence of a distinct and integrated hormone-mediated corticolimbic homeostatic, although maladaptive and pathological, state in major depression. © 2010 Gaiteri et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Gaiteri, C
Guilloux, JP
Lewis, DAtnplewis@pitt.eduTNPLEWIS
Sibille, E
Centers: Other Centers, Institutes, Offices, or Units > Center for Neuroscience
Date: 13 September 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0009970
Refereed: Yes
MeSH Headings: Amygdala--metabolism; Brain--metabolism; Brain Chemistry; Cerebral Cortex--metabolism; Depressive Disorder, Major--genetics; Gene Expression Regulation; Homeostasis; Hormones--physiology; Humans; RNA, Messenger--analysis
Other ID: NLM PMC2848620
PubMed Central ID: PMC2848620
PubMed ID: 20376317
Date Deposited: 03 Aug 2012 18:54
Last Modified: 02 Feb 2019 16:56


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