Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients

PLoS One. 2014 Mar 11;9(3):e91076. doi: 10.1371/journal.pone.0091076. eCollection 2014.

Abstract

Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD) and bipolar disorder (BPD). These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90) and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35). The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif) ligand 24 (CCL24) which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6) which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biomarkers
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Case-Control Studies
  • Chemokine CCL24 / genetics
  • Chemokine CCL24 / metabolism
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / metabolism
  • Diagnosis, Differential
  • Female
  • Gene Expression Profiling
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Middle Aged
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism
  • Reproducibility of Results
  • Risk Factors
  • Signal Transduction
  • Transcriptome*

Substances

  • Biomarkers
  • Chemokine CCL24
  • Cytokines
  • Inflammation Mediators
  • Receptors, CCR6

Grants and funding

The GENDEP project was funded by the European Commission Framework 6 Grant, EC Contract Ref. LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the GENDEP project. The BACC Study collection was funded by GlaxoSmithKline. The current study was financially supported by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London, under the Grant BRC 08/09PP. The funders had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing the report. Timothy R. Powell is funded by a Medical Research Council PhD studentship.