Biomarker discovery for early-onset Major Depressive Disorder

Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy Transl Psychiatry. Aug 2014;

An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls.

Patients with MDD received cognitive behavioral therapy (CBT). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT.

Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed.

Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

This study has a number of limitations. These include the modest sample size. In addition, there were only two samples for each MDD subject, and only one ND sample.

Conclusions

This study identified nine transcripts that differentiated depressed from nondepressed participants, three of which can distinguish subjects with MDD from nondepressed controls, even after remission. A three-transcript panel discerned remitted from non-remitted patients post CBT, and concomitant abundance differences in some transcripts at baseline might indicate treatment responsiveness a priori.

Thus, blood levels of different transcript panels may be useful in identifying depressed primary care patients, as well as in predicting and monitoring response to CBT. Future studies are aimed at validating these results in a larger patient population and determining the selectivity of these panels in patient population that include other psychiatric illnesses.

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression  Transl Psychiatry. Apr 2012

Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective.

Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD.

A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths.

These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies

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