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Biomarkers could help diagnose MDD.


Analyses of blood RNA in a study of 64 patients with or without major depression showed significant differences in gene transcript levels between groups, in ways that suggest blood transcriptomic markers may provide an objective way to diagnose depression, predict response to cognitive-behavioral therapy, and identify people with a predisposition to depression.

As a secondary part of a randomized study comparing the efficacy of 18 weeks of live versus telephone-based cognitive-behavioral therapy, investigators studied a panel of blood transcriptomic markers before treatment in 32 patients with major depressive disorder and 32 matched controls without depression, and in 22 patients in each group after treatment.

The abundance of nine transcripts differed significantly between groups at baseline, suggesting that a panel of transcriptomic markers could be diagnostic in a clinical population, Eva E. Redei, Ph.D., and her associates reported (Transl. Psychiatry 2014 Aug. 16 [doi: 10.1038/tp.2014.66]).

These markers include adenylate cyclase 3 (ADCY3); diacylglycerol kinase, alpha (DGKA); family with sequence similarity 46, member A (FAM46A); immunoglobulin superfamily, member 4 (IGSF4), which also is known as cell adhesion molecule 1 (CADM1); KIAA1539; myristoylated alanine-rich protein kinase C substrate (MARCKS); proteasome activator subunit 1 (PSME1); Ras association and pleckstrin homology domains 1, also known as LPD (RAPH1); and intracellular Toll-like receptor 7 (TLR7).

After cognitive-behavioral therapy, the abundance of five transcripts--DGKA, IGSF4A/CADM1, KIAA1539, MARCKS, and RAPH1-remained significantly different between the two patient groups.

Receiver-operating characteristic (ROC) analyses of blood transcript levels showed that RAPH1, KIAA1539, and DGKA also had significant areas under the curve (AUC) in the depressed patients after cognitive-behavioral therapy both in the 9 patients who achieved a full remission of disease and in the 13 patients who did not.

"These markers come closest to the ultimate goal of identifying predisposition to depression, even in the absence of a current depressive episode," reported Dr. Redei, professor in psychiatry and behavioral sciences, and physiology at Northwestern University, Chicago.

In addition, coexpression patterns of transcripts might help predict remission or persistence of clinical depression after cognitive-behavioral therapy.

Patients whose depression remitted had 11 "hubs" of co-expressed gene-pairs that correlated significantly with three or more transcripts, compared with five hubs in patients who did not achieve remission.

Transcript levels of ADCY3, DGKA, IGSF4A/CADM1, PSME1, and RAPH1 significantly correlated in their expression at baseline in patients whose disease remitted after treatment but not in patients who remained clinically depressed after treatment. On Twitter @sherryboschert


Key clinical point: Blood levels of transcript panels differentiated depressed patients from controls.

Major finding: Blood transcript levels of nine markers differed significantly between groups.

Data source: Secondary analyses from a study of 32 depressed patients and 32 nondepressed subjects.

Disclosures: Dr. Redei is named as an inventor on two pending patent applications. She and her associates reported having no other financial disclosures. The National Institute of Mental Health and the Davee Foundation funded the study.
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Author:Boschert, Sherry
Publication:Clinical Psychiatry News
Date:Oct 1, 2014
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