Depression, the most prevailing mental health condition, remains untreated in over 30% of patients. This cluster presents with sub-clinical inflammation. Investigations trialling anti-inflammatory medications had mixed results. The lack of results may result from inflammation's complexity and targeting only a few of depression's abnormal pathways. Mind-body therapies' biological and neuro-imaging studies offer valuable insights into depression psychopathology. Interestingly, mind-body therapies, like yoga, reverse the aberrant pathways in depression. These aberrant pathways include decreased cognitive function, interoception, neuroplasticity, salience and default mode networks connectivity, parasympathetic tone, increased hypothalamic-pituitary-adrenal (HPA) axis activity, and metabolic hyper/hypofunction. Abundant evidence found yogic techniques improving self-reported depressive symptoms across various populations. Yoga may be more effective in treating depression in conjunction with pharmacological and cognitive therapies. Yoga's psychoneuroimmunology teaches us that reducing allostatic load is crucial in improving depressive symptoms. Mind-body therapies promote parasympathetic tone, downregulate the HPA axis, reduce inflammation and boost immunity. The reduced inflammation promotes neuroplasticity and, subsequently, neurogenesis. Improving interoception resolves the metabolic needs prediction error and restores homeostasis. Additionally, by improving functional connectivity within the salience network, they restore the dynamic switching between the default mode and central executive networks, reducing rumination and mind-wandering. Future investigations should engineer therapies targeting the mechanisms mentioned above. The creation of multi-disciplinary health teams offering a combination of pharmacological, gene, neurofeedback, behavioural, mind-body and psychological therapies may treat treatment-resistant depression.
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