Most people are still locked into the theory that depression is caused by a chemical imbalance in the brain ? a shortage of feel-good neurotransmitters like serotonin that deliver messages from one neuron to another. That explanation works well for public consumption because it’s simple and it makes for great pharmaceutical commercials.

But depression is a whole lot more complicated than that.

For starters, there’s faulty brain wiring. On functional MRIs, depressed brains display lower activity levels in the frontal lobes, responsible for cognitive processes, and higher levels of activity in the amygdala region of the brain (fear central). Depression can be associated with the loss of volume in parts of the brain, namely the hippocampus, which belongs to the limbic system (the emotional center of the brain). The more severe the depression, the greater the loss of brain volume. The endocrine system plays a significant role in mood disturbances. Some studies on depression have indicated a default in the hypothalamic-pituitary-adrenal (HPA) axis, the region that manages the body’s response to stress. Chronic activation of the HPA is no good, as anyone with thyroid or pituitary issues will tell you.

And there’s another theory has been lurking in the background for quite awhile, but is finally gaining the trust and attention of the public: that depression is an allergic reaction to inflammation.

The first time I read this ? in the bestseller The UltraMind Solution by Mark Hyman, MD, ? I had trouble believing it. At that point, I had spent eight years researching and writing about depression, closely following the studies published by Johns Hopkins Medical School, because their Mood Disorders Center (and my skilled psychiatrist) saved me from severe, suicidal depression.

However, I continued to be bothered by the fact that one-third of people with major depression don’t respond to antidepressants, even after trying multiple options. Two years after my initial remission from depression, in 2006, I fell into that category myself. And I didn’t seem to respond all that dramatically to sessions of psychotherapy either. Or mindfulness programs.

So a year and a half ago, I began to entertain the idea that some types of depressions could very well be caused by inflammation, and therefore might require remedies other than medication, psychotherapy, and mindfulness.

A piece by Caroline Williams in The Guardian cites the growing number of studies that suggest depression is, in fact, a result of inflammation. One study published in the Journal of Affective Disorders found that both depression and mania are associated with pro-inflammatory states. A spike in cytokines, proteins that are pumped into our blood stream when our immune system is fighting off a foreign agent, happens when people are depressed. The process looks the same as when a person is fighting an infection of any kind. A study published in Biological Psychiatry reported that brain images of volunteers injected with a typhoid vaccine, which produces robust inflammation, showed changes in the prefrontal regions of the brain that affect motivation and concentration.

Williams builds the case: “There are other clues, too: people with inflammatory diseases such as rheumatoid arthritis tend to suffer more than average with depression; cancer patients given a drug called interferon alpha, which boosts their inflammatory response to help fight the cancer, often become depressed as a side-effect.”

But what is causing the inflammation?

Researchers name a host of possibilities ranging from infections, such as the flu, to diets high in sugar and trans fats, to bullying and loneliness. In my case, the suspect is painfully obvious: carbohydrates composed of carbon, hydrogen, and oxygen … a.k.a the legal white powder that is a hidden ingredient in most of our foods.

Dr. Hyman, also author of The Blood Sugar Solution, writes: “By far the most important factor in brain aging and inflammation in America is sugar. The sheer flood of sweet things and processed refined foods into our bodies is a tidal wave that leaves destruction everywhere we look … The insulin triggered by this flood of sugar sets into motion an entire inflammatory parade.”

Sugar and foods like potatoes and pasta, Hyman asserts, turn on the “cellular switches” that increase cytokines, just like when we have the flu or a urinary tract infection. “There is no scientific controversy here,” he writes. “The evidence is in. Sugar causes inflammation. The insulin-resistant fat cells you pack on when you eat too much sugar produce nasty inflammatory messengers (cytokines) … spreading their damage to the brain.”

I thought he was exaggerating the evil powers of the Oreo until I stopped eating sugar (plus anything made with white flour) cold turkey one day last year. I went months without it, but thought I deserved a piece of pumpkin pie on Thanksgiving. It took a few hours to get into my system, but once the cytokines were swimming in my blood stream, all I could think about for the next 48 hours was the quickest exit out of this life.

Coincidence?

On Memorial Day weekend, I slipped again. My daughter couldn’t eat her entire Nutty Buddy — those irresistible vanilla ice-cream cones dipped in chocolate and peanuts. With my favorite dessert sitting right in front of me, I begin to think, “Maybe I didn’t react to the pumpkin pie on Thanksgiving. Maybe it was something else.” Satan then whispered into my ear, “How can something so luscious make you so sad?”

I had nine bites.

I counted them.

I also had baked beans (sugar), coleslaw (sugar), and eight breaded chicken nuggets from Chick-fil-A (sugar).

And then I endured four days of intense death thoughts, wondering if I prayed hard enough maybe God would kindly exchange my body and soul with a child in heaven who wasn’t meant to die. I started doing death math again, figuring if the median age of death for my ancestors is 82, then I had approximately 37.5 more years to hang in there. I compared life to a marathon: I only had 12 more miles to run!

“This is crazy!” I thought to myself.

But I’m hardly alone.

Once my brain stopped obsessing about death, I posted my holiday experiment in my depression communities, ProjectBeyondBlue.com and Group Beyond Blue, and on my Facebook page, and was taken aback by the enlightened responses of fellow members.

“I experience suicidal depression whenever I eat sugar or any other simple carb,” one woman explained. “I do many things to manage my depression, but this is the most important piece of my plan. I haven't eaten any sugar or other problem carbs for many years now. I have absolutely no interest in desserts. The cost is way too large.”

“I can barely function if I eat dairy,” another wrote. “Especially cheese. The first 24 hours after I eat it, I feel drunk. But a few days later, I can barely think straight, and my depression goes through the roof. I feel guilt and shame over things that are long past and forgiven. I even have a hard time talking, forming sentences, etc. It usually takes five days to completely clear out of my system.”

All of this is incredibly fascinating to me because this kind of science could eventually provide relief to the considerable chunk of people that don’t respond to antidepressants. Williams explains that a few clinical trials so far have found that adding anti-inflammatory medicines to antidepressants improves symptoms and increases the proportion of people who respond to treatment. She says there is also some evidence that omega-3s and curcumin might have similar effects.

Some experts like Turhan Canli, PhD, are going so far as to try to brand depression as an infectious (but not contagious) disease.

That might take awhile.

In the meantime, I’m staying away from the Nutty Buddy.

It certainly isn’t my buddy.

Join the discussion "Depression Is a Reaction to Inflammation" on ProjectBeyondBlue.com, the new depression community.