Abstract:
BACKGROUND:Major depressive disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. METHODS:We used a classifier approach on blood gene expression profiles of a unique set of unmedicated subjects (MDD patients and control subjects) to select genes with expression predictive for disease status. To reveal blood gene expression changes related to major depressive disorder-disease, we applied a powerful ex vivo stimulus to the blood: incubation with lipopolysaccharide (LPS; 10 ng/mL blood). RESULTS:Based on LPS-stimulated blood gene expression using whole-genome microarrays (primary cohort; 21 MDD patients, 21 healthy control subjects), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated using an independent quantitative polymerase chain reaction method (primary cohort, p = .007). The difference between depressive patients and control subjects was confirmed (p = .019) in a replication cohort of 13 MDD patients and 14 control subjects. The MDD signature score comprised expression levels of seven genes could discriminate depressive patients from control subjects with sensitivity of 76.9% and specificity of 71.8%. CONCLUSIONS:We have shown for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of major depressive disorder.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Spijker S,Van Zanten JS,De Jong S,Penninx BW,van Dyck R,Zitman FG,Smit JH,Ylstra B,Smit AB,Hoogendijk WJdoi
10.1016/j.biopsych.2010.03.017subject
Has Abstractpub_date
2010-07-15 00:00:00pages
179-86issue
2eissn
0006-3223issn
1873-2402pii
S0006-3223(10)00246-5journal_volume
68pub_type
杂志文章abstract:BACKGROUND:Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2011.03.026
更新日期:2011-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-09-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:1998-10-01 00:00:00
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更新日期:2001-12-01 00:00:00
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更新日期:2006-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1984-02-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2006-05-01 00:00:00