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

PLoS One

Georgina M. Hosang¹  Anne E. Farmer²  Richard K. Day²  Ursula M. D'Souza³  Keith Matthews³  Peter McGuffin³  Timothy R. Powell³  Charlotte Martin³  Leonard C. Schalkwyk³  Sarah Cohen-Woods³  Katherine E. Tansey³ 

[1] Discipline of Psychiatry, University of Adelaide, Adelaide, Australia;Division of Neuroscience, Ninewells Hospital and Medical School, Dundee, United Kingdom;King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom

关键词: Biomarkers;    Depression;    Cytokines;    Mood disorders;    Blood;    Chemokines;    DNA transcription;    Inflammatory diseases;   

DOI  :  10.1371/journal.pone.0091076

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY