Developing a translational research framework for MDD: combining biomolecular mechanisms with a spiraling risk factor...

Area of Science:

• Neuroscience
• Psychiatry
• Microbiology

Background:

• Major Depressive Disorder (MDD) incidence is rising globally, with 30-40% of patients unresponsive to current treatments.
• The microbiota-gut-brain axis (MGBA) presents potential novel therapeutic targets for MDD.
• Integrating MGBA with psychological and environmental factors in MDD is challenging.

Purpose of the Study:

• Investigate MDD's biomolecular mechanisms using a modeling approach.
• Develop a comprehensive 'spiraling risk factor model' for MDD.
• Establish a biopsychosocial translational research framework for MDD prevention and treatment.

Main Methods:

• Systematic literature review (PubMed, Embase, Scopus, 2016-2020) for biomolecular mechanisms.
• Narrative review to integrate findings into a biopsychosocial model.
• PROSPERO registration (CRD42020215412) ensured methodological rigor.

Main Results:

• HPA axis hyperactivation and inflammation are key MGBA components in MDD.
• MGBA dysregulation, alongside lifestyle and mental/physical health imbalances, can initiate a stress-anxiety spiral leading to MDD.
• MDD is a heterogeneous condition influenced by biomolecular, psychological, and environmental factors.

Conclusions:

• MDD is a complex disorder, not solely brain-related.
• Future research should focus on interdisciplinary, biopsychosocial insights.
• Develop lifestyle-focused, multimodal interventions for MDD treatment, diagnosis, and prevention.