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In MDD, this peripheral-central coupling is likely amplified by BBB dysfunction characterized by increased permeability, neurovascular inflammation, and associations with symptom severity [172, 173] thereby lowering the threshold at which peripheral KP activation translates into central glutamatergic, oxidative, and neuroimmune dysregulation

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10.1083/jcb.201708007 86 WongD

Vitamin B12 deficiency can present with a range of physical and neurological symptoms

However, it should be noted that patients may evaluate drugs differently during actual treatment, and the impact of these various factors in practice may be less than patients anticipate