title: Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients.
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.
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Powell
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Ursula M
authors.initials: UM
authors.lastname: D'Souza
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen-Woods
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Hosang
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.affiliation: Division of Neuroscience, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Matthews
authors.affiliation: Division of Neuroscience, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Day
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Farmer
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.affiliation: King's College London, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, London, United Kingdom.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D054423:Chemokine CCL24 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012307:Risk Factors; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D054423:Chemokine CCL24; D016207:Cytokines; D018836:Inflammation Mediators; D054399:Receptors, CCR6