title: MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c.
abstract: There is a growing emphasis in the field of psychiatry on the need to identify candidate biomarkers to aid in diagnosis and clinical management of depression, particularly with respect to predicting response to specific therapeutic strategies. MicroRNAs are small nucleotide sequences with the ability to regulate gene expression at the transcriptomic level and emerging evidence from a range of studies has highlighted their biomarker potential. Here we compared healthy controls (n=20) with patients diagnosed with major depression (n=40) and who were treatment-resistant to identify peripheral microRNA biomarkers, which could be used for diagnosis and to predict response to electroconvulsive therapy (ECT) and ketamine (KET) infusions, treatments that have previously shown to be effective in treatment-resistant depression (TRD). At baseline and after treatment, blood samples were taken and symptom severity scores rated using the Hamilton Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression using microarray and validated using quantitative PCR. As expected, both treatments reduced HDRS scores. Compared with controls, the baseline expression of the microRNA let-7b was less by ~40% in TRD patients compared with controls. The baseline expression of let-7c was also lower by ~50% in TRD patients who received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has previously been reported to be dysfunctional in depression. The expression of miR-16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline microRNA expression could not predict treatment response and microRNAs were unaffected by treatment. Taken together, we have identified let-7b and let-7c as candidate biomarkers of major depression.
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Gururajan
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.|St Patrick's University Hospital, Dublin, Ireland.
authors.forename: M E
authors.initials: ME
authors.lastname: Naughton
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: K A
authors.initials: KA
authors.lastname: Scott
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: R M
authors.initials: RM
authors.lastname: O'Connor
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Moloney
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Dowling
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Walsh
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
authors.forename: F
authors.identifier: 0000-0002-7019-2146
authors.initials: F
authors.lastname: Ismail
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Shorten
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Scott
authors.affiliation: St Patrick's University Hospital, Dublin, Ireland.|Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: D M
authors.initials: DM
authors.lastname: McLoughlin
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: J F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: T G
authors.initials: TG
authors.lastname: Dinan
mesh_terms: D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000628:therapy; D061218:Depressive Disorder, Treatment-Resistant / Q000378:metabolism* / Q000628:therapy; D004565:Electroconvulsive Therapy / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C487931:mirnlet7 microRNA, human; C546842:MTOR protein, human