Lost in translation. The quest for definitions of treatment-resistant depression with a focus on inflammation-related gene expression

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Major depressive disorder (MDD) affects a significant portion of the population.
• Approximately one-third of MDD patients exhibit non-response to standard antidepressant treatments, a condition known as treatment-resistant depression (TRD).
• Current definitions and understanding of TRD lack comprehensive clinical and operational criteria.

Purpose of the Study:

• To provide an overview of the current clinical and operational criteria for defining treatment-resistant depression (TRD).
• To highlight knowledge gaps and open questions in TRD research.
• To emphasize the need for biological and molecular correlates in defining TRD.

Main Methods:

• Literature review and synthesis of existing clinical and operational definitions of TRD.
• Analysis of current research on biological and molecular correlates of antidepressant non-response.
• Exploration of potential biomarkers, including inflammation-related gene expression signatures.

Main Results:

• Existing definitions of TRD are insufficient and require refinement.
• Inflammation-related gene expression signatures show promise as potential biomarkers for TRD.
• A significant gap exists in understanding the biological underpinnings of non-response to depression treatments.

Conclusions:

• A refined definition of TRD is essential for advancing research and clinical practice.
• Incorporating biological and molecular data, such as inflammation markers, is critical for a more accurate TRD characterization.
• Identifying biologically distinct MDD phenotypes could lead to more effective, targeted treatments.