Peripheral biomarkers of major depression and antidepressant treatment response: Current knowledge and future outlooks

Abstract

Background: In recent years, we have accomplished a deeper understanding about the pathophysiology of major depressive disorder (MDD). Nevertheless, this improved comprehension has not translated to improved treatment outcome, as identification of specific biologic markers of disease may still be crucial to facilitate a more rapid, successful treatment. Ongoing research explores the importance of screening biomarkers using neuroimaging, neurophysiology, genomics, proteomics, and metabolomics measures.

Results: In the present review, we highlight the biomarkers that are differentially expressed in MDD and treatment response and place a particular emphasis on the most recent progress in advancing technology which will continue the search for blood-based biomarkers.

Limitations: Due to space constraints, we are unable to detail all biomarker platforms, such as neurophysiological and neuroimaging markers, although their contributions are certainly applicable to a biomarker review and valuable to the field.

Conclusions: Although the search for reliable biomarkers of depression and/or treatment outcome is ongoing, the rapidly-expanding field of research along with promising new technologies may provide the foundation for identifying key factors which will ultimately help direct patients toward a quicker and more effective treatment for MDD.

Keywords: Biomarkers; Biosignatures; Depression; Genomics; Metabolomics; Proteomics.

Figure 1. Biomarkers of major depression

Biomarkers identified before treatment initiation are classified as diagnostic, predictive, or moderators. Diagnostic markers classify an MDD patient, predictive markers determine overall likelihood of response/remission, and moderators determine likelihood of response/remission with a particular treatment. Mediators are biomarkers collected soon after treatment initiation and help predict overall likelihood of response/remission. Long-term treatment response may also be indicative of ultimate outcome

Figure 2. Tools and Technologies for the development biomarker candidates

Biomarker consists of four main phases- discovery, qualification, verification and validation. The tools and associated technologies are listed for pharmacogenomics, epigenetics, transcriptomics, proteomics and metabolomics. “Analytes” and “Samples” refer to the number of different protein targets or samples, respectively that are evaluated in each phase. LC-MS/MS, liquid chromatography tandem mass spectrometry; NGS, Next generation sequencing; PCR, Polymerase chain reaction.

Figure 3. ‘Omics based approach in major depression and treatment matching

Along with imaging and physiology, ‘omics’ and clinical phenotype are major components which may lead to treatment matching via unique biosignature. ‘Omics include: genomics, proteomics, transcriptomics, epigenomics, and metabolomics. Phenotype includes social, clinical and behavioral. Overall, evaluation of these features may enable identification of different subtypes of depression, which may improve treatment matching.