Dr. Greenblatt’s Take on Root Causes and Depression

A leader in functional psychiatry looks for root causes to explain why a third of depressed patients don’t respond to standard care

STUDY: Greenblatt J Advances in Mind-Body Medicine 2026
STUDY TYPE: Expert interview.
FUNDING: Independent

Background

James Greenblatt is a leader in functional psychiatry, which aims to find root causes of psychiatric disorders, such as vitamin deficiencies, hormone imbalance, or an unhealthy gut. His new book, Finally Hopeful, makes the case for that, and he gave a recent interview on the subject in a medical journal.

Summary

• Greenblatt discusses his 30-year clinical experience treating depression through nutritional and metabolic testing.
• He highlights specific deficiencies tied to mood: vitamin D (a cofactor for serotonin synthesis), B12, folate, zinc, and magnesium, low cholesterol (total cholesterol under 130 is associated with suicidality), and low dietary omega-3s.
• He also reviews gut-brain signaling, amino acid precursors for neurotransmitters, and lithium’s neuroprotective effects, including a 2025 Harvard study showing lithium orotate reversed Alzheimer’s pathology in mice.
• Greenblatt uses this same testing approach to ease antidepressant withdrawal by correcting micronutrient deficits before tapering.

Practice Implications

1. Greenblatt’s approach is based on a mix of theory and clinical research, most of the steps he recommends are backed by clinical trials. They are low cost and low-risk.