Reverse-engineering depression

What do you do when you’re chronically depressed, and conventional treatment doesn’t help? Almost every single day, I’d think about ending my life. A few half-arsed attempts left me with unsightly scars, traumatized friends, and stacks of medical bills. I didn’t actually wish to die, but a life deprived of joy wasn’t very appealing.

I was in and out of mental hospitals, often involuntarily. I had to go on disability leave, since I could no longer do my job. I was in partial hospitalization programs, had weekly appointments with my psychiatrist and with my therapist. I tried a lot of psychotropic drugs, DBT, and ECT. Nothing seemed to help.

At this point, I started questioning what I’d been told by doctors, that it’s all due to low levels of serotonin, or neurotransmitter imbalance in general. Even if they were right, I wanted to know why, so I hit the books.

Let’s read some research

I started reading all the depression research I could get my hands on, and found several interesting theories. I read about the connection between inflammation and depression, and how arthritis drugs were effective for some, due to their anti-inflammatory properties.

This seemed like an interesting direction, because many of the hypothesized etiologies applied to me, and there were plenty of things I could actually test for. It dawned on me that, during the course of my treatment, no actual tests had been performed1.

My doctor at the time was very rude and dismissive, perhaps rightly so. I’m probably not the first patient who read something on the internet and formed a half-baked hypothesis. However, he wanted to put me on yet another SSRI, so I said no thanks, and got a new doctor.

A doctor not averse to testing.

Test-driven depression treatment

I prepared my case, brought all my research, and went to my first appointment with my new doctor. I described my symptoms, and she did a physical exam. She then put forth a more developed version of what I was about to present. Perhaps not surprising, her being an actual doctor and all.

This was an incredibly validating experience, and one that made me feel like I was in good hands, knowing that she was familiar with the stuff I’d been reading about. She wrote me a lab slip for the tests I’d been wanting to do, and then some.

Taking a more scientific approach to depression treatment made it feel like something that could be fixed, rather than this nebulous thing that doesn’t obey the laws of our universe. There was a glimmer of something that had been absent for a long time: hope.

Inflammation, mutation, and mitigation

At my second appointment, we went over the test results. While there were signs of inflammation, what caught her eye were numerous signs of a methylation issue. I’d come across this in my reading, but it wasn’t something I’d really dug into, until now. My doctor wrote another lab slip, recommended a couple of supplements, and put me on a special diet.

I read up on the methylation cycle, and how it’s directly involved in the production of all those neurotransmitters implicated in depression. Through my therapist, I heard about a genetic mutation that affects methylation, and how one of her clients used Deplin to treat it.

While looking into genetic testing, I remembered doing that 23andMe thing some time ago. I downloaded the raw data, and searched for the MTHFR gene. Sure enough, it looked like a homozygous mutation. I wasn’t sure if my interpretation was correct, so I used a couple of tools to check it2.

I looked into Deplin, and found that it’s just L-methylfolate, which is available over-the-counter. My specific mutation, however, is associated more with BH4 issues3, so I ordered some supplements tailored for this.

Mission accomplished

Eh, not really. In hindsight, trying to reverse-engineer a complex and poorly understood illness seems a bit unrealistic. I still consider it a success, though; I figured out one little piece of the puzzle, and I feel better on this treatment than I ever did on antidepressants.

I’m no longer suicidal, I’m back at work, I picked some hobbies back up, and I get a bit of enjoyment out of things again. There’s a long way to go, but this was a critical first step.


  1. Other than for hypothyroidism, which I had to self-diagnose and ask for myself. ^
  2. Genetic Genie and Promethease, both accept 23andMe data. ^
  3. Wikipedia. Tetrahydrobiopterin deficiency § 2.1. ^

Published in mental-health, personal

Copyright © 2017 Alva