What Are Promising Biomarkers for Predicting Treatment Response in Resistant Depression?

What you need to know

• Treatment-resistant depression (TRD) affects 30-40% of patients with major depression, but there are no established biomarkers to predict treatment response.
• Some inflammatory markers like IL-6 and CRP show potential as predictive biomarkers, but results are inconsistent across studies.
• Factors like BDNF, endocrine markers, and metabolic markers have also been investigated, with mixed results.
• Larger studies are needed to validate potential biomarkers and account for different TRD subtypes.

Inflammatory and Immune Biomarkers

Several inflammatory markers have been studied as potential predictors of treatment response in TRD:

• Interleukin-6 (IL-6): Some studies found higher baseline IL-6 levels predicted better response to ketamine or ECT, while others found no association. Results are inconsistent.

• C-reactive protein (CRP): Higher baseline CRP levels have been associated with better response to some treatments like infliximab in TRD patients. However, results are mixed across studies.

• Tumor necrosis factor-alpha (TNF-α): Most studies found no predictive value of baseline TNF-α levels for treatment response in TRD.

• Other cytokines like IL-1β, IL-8, IL-10, and IFN-γ have shown little evidence as predictive biomarkers so far.

The authors note that inflammatory markers may be most useful for predicting response to anti-inflammatory treatments specifically in TRD patients with elevated inflammation.

Neurotrophic Factors

Brain-derived neurotrophic factor (BDNF) has been extensively studied:

• Most studies found no association between baseline BDNF levels and treatment response in TRD.
• A few studies found higher baseline BDNF predicted better ECT response.
• The BDNF Val66Met polymorphism may be associated with response to brain stimulation treatments.

Other growth factors like vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) have shown some potential in limited studies.

Endocrine Biomarkers

The hypothalamic-pituitary-adrenal (HPA) axis has been investigated:

• Some evidence that baseline cortisol/DHEA ratio may predict treatment response.
• Mixed findings on whether higher or lower baseline cortisol predicts response.
• More research is needed on dynamic HPA axis measures.

Metabolic Biomarkers

Limited studies have looked at:

• Adipokines: Lower baseline adiponectin predicted better ketamine response in one small study.
• Lipid markers: Mixed findings on whether higher or lower baseline cholesterol predicts response.

Other Biomarkers

Exploratory studies have examined markers like p11 protein, D-serine, and oxidative stress markers, but more research is needed to validate their predictive value.

Conclusions

• No single biomarker has shown consistent predictive value for treatment response in TRD.
• Larger studies accounting for TRD subtypes are needed to validate potential biomarkers.
• A combination of biomarkers along with clinical factors may be most useful for predicting treatment outcomes.
• Identifying reliable biomarkers could improve personalized treatment selection and development of new therapies for TRD.