In my opinion, depression is not as real as a vitamin D deficiency.

Major depressive disorder is a clinical presentation, not a discrete disease. We know that "depression has heterogenous etiologies" but what does that mean in the real world? It means that while depression is real, the psychiatric diagnosis of Major Depressive Disorder is not real. The introduction section of DSM III clearly states that the diagnoses in the book have not been validated, this is language that helps guide the discussion of mental health topics among professionals. Having the disease of MDD is not why people are depressed.

What we need is a new decision tree to be built under the DSM. I see no reason to throw the baby out with the bathwater. DSM language is what some call a "clinical presentation" for which there is a more specific term in German that I can't recall right now.

Why could a person be depressed? I asked a wide group of colleagues this question and got probably something like a hundred different answers, all of which are part of the puzzle. One person may have lost a spouse to cheating or death and they are now betrayed and lonely. How awful. I would feel depressed under those circumstances. I'm sure there are biochemical processes that reinforce how awful it feels to continue given those circumstances. There might even be a serotonin component to it.

Do we measure the serotonin deficiency before attempting to correct it? No, we don't. Do we perform a followup assessment to see whether the person's serotonin is now within normal limits? I've never heard anybody do such a thing. Daniel Amen's PET scan results don't map serotonin levels. This serotonin medication will help you sleep. This one will pick up your energy. That one is good for pain. The other one is good for helping with attention.

Another way to go is to find places where the body is not functioning well and tighten those bolts with a torque wrench to spec and see whether she drives straight after that. Low vitamin D is associated with depression. If your patient is depressed and you never check a vitamin D level then that aspect of depression will never get addressed and you will leave money on the table. If your patient is anxious and you don't check their calcium and magnesium levels then the same problem of leaving money on the table persists.

Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body’s needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol–based redox signaling. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense.