Putative Transcriptomic Biomarkers in the Inflammatory Cytokine Pathway Differentiate Major Depressive Disorder Patients from Control Subjects and Bipolar Disorder Patients

• Published in: PloS one Vol. 9; no. 3; p. e91076
• Main Authors: Powell, Timothy R., McGuffin, Peter, D'Souza, Ursula M., Cohen-Woods, Sarah, Hosang, Georgina M., Martin, Charlotte, Matthews, Keith, Day, Richard K., Farmer, Anne E., Tansey, Katherine E., Schalkwyk, Leonard C.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.03.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis of Variance; Biological markers; Biology; Biomarkers; Bipolar disorder; Bipolar Disorder - diagnosis; Bipolar Disorder - genetics; Bipolar Disorder - metabolism; Case-Control Studies; CCR6 protein; Chemokine CCL24 - genetics; Chemokine CCL24 - metabolism; Chemokines; Clinical decision making; Complementary DNA; Cytokines; Cytokines - genetics; Cytokines - metabolism; Decision making; Deoxyribonucleic acid; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - genetics; Depressive Disorder, Major - metabolism; Diagnosis, Differential; Diagnostic systems; Disorders; DNA; Drugs; Etiology; Female; Gene expression; Gene Expression Profiling; Genes; Genetic research; Humans; Illnesses; Inflammation; Inflammation Mediators - metabolism; Major depressive disorder; Male; Medical research; Medicine; Mental depression; Middle Aged; Mood; Neurosciences; Patients; Primers; Psychiatry; Psychopathology; Receptors, CCR6 - genetics; Receptors, CCR6 - metabolism; Reliability analysis; Reproducibility of Results; Ribonucleic acid; Risk Factors; RNA; Signal Transduction; Studies; Transcription; Transcription (Genetics); Transcriptome; Tumor necrosis factor-TNF; Variance analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091076

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.