Climbing Out of the Depression Hole: Kick Pills, Bring Back Aliveness

For this article by Sara Gottfried MD on Depression the image shows a man sitting on the floor holding his head in his hands.

I have been treating depression for about 25 years, so when a friend mentioned feeling depressed while on a hike with me, I jumped into doctor mode: “How’s your diet? How’s your gut? How’s your inflammation?”

My friend stared back at me, dumbfounded. “What does my gut have to do with my bad mood?”

Tons. Deep diagnostics and personalized medicine can really help people who suffer from depression.

When most people think of depression, they don’t think of the body and its role in creating a depressed mood. They think of what the pharmaceutical companies want us to think, i.e., a chemical imbalance in the brain—maybe low serotonin and/or norepinephrine—and how a prescription might help.

But what if depression was a symptom of something else, like inflammation? That is, what if depression is actually an inflammation disorder in the body that begins in the gut and then seeps into the brain, not a disease? Yes, depression is like other brain complaints like anxiety, foggy thinking, weight gain, memory loss—a symptom of inflammation from a brain body out of balance.

The Grim Statistics of Depression

Major depression is one of the most common mental illnesses in the United States and globally, and can interfere with or limit daily activities.

  • Globally, at least 5 percent of the population suffers from depression.1
  • In the United States, according to the National Institute of Mental Health, 21 million adult Americans, or 8.4 percent of the adult population have at least one episode of major depression each year.2
  • Prevalence in women is higher (10.5 percent) than in men (6.2 percent).3
  • Over your lifetime, your risk of developing depression is approximately 21 to 45 percent for women and 10 to 30 percent for men.4
  • Given that your risk of depression is linked to inflammation, it’s not surprising that diabetes is associated with a 5-fold greater risk of depression.5
  • Covid has increased prevalence. Among adolescents globally, aged 10-19, approximately 34 percent are at risk of developing clinical depression, which is higher than recorded rates in individuals aged 18 to 25.6
  • Rates are highest in the United States and lowest in Asian countries, with the median age of onset around 32 years.
  • Depression is the leading cause of disability for US adults ages fifteen to forty-four, the leading cause of disability worldwide, and one of the top global health issues.

Do You Have Depression?

The following questionnaire is called the PHQ-9, a series of nine questions validated to be very reliable at diagnosing depression, as accurate as a structured interview with a mental health professional. The best way to use it is to assign a relative weight to your answer for each question as follows: 

0 for not at all
1 for several days in the past two weeks
2 for more than half the days
3 for nearly every day

Fill in your score for each question, then tally each score at the end. 

Over the last two weeks, how often have you been bothered by any of the following problems: 

  1. Little interest or pleasure in doing things? 
  2. Feeling down, depressed, or hopeless? 
  3. Trouble falling or staying asleep, or sleeping too much? 
  4. Feeling tired or having little energy? 
  5. Poor appetite or overeating? 
  6. Feeling bad about yourself—or that you are a failure or have let yourself or your family down? 
  7. Trouble concentrating on things, such as reading the newspaper or watching television? 
  8. Moving or speaking so slowly that other people could have noticed? Or the opposite—being so fidgety or restless that you have been moving around a lot more than usual? 
  9. Thoughts of hurting yourself in some way or that you would be better off dead? 

The first two questions are the most important in screening for depression, but the entire questionnaire can inform you about depression severity and whether you should consider seeing a clinician (and inform your health care professional). Here’s how to interpret your results.

0−4 points, minimal or no depression
5−9 points, mild depression: consider discussing symptoms with a primary care doctor or mental health professional.
10−14 points, moderate depression (10 or more points classify you as having major depression, which includes moderate and severe categories): definitely time to see your health care professional.
15−19 points, moderately severe depression: see a clinician to discuss your symptoms.
20−27 points, severe depression: similarly, see a clinician to discuss.

Root Cause of Depression

I consider depression to be a gut/brain axis a failure state that can lead to depression. When your brain is tired, weary, overtaxed, and overstressed, there’s a downward spiral, but many of the reasons your brain gets overtaxed in the first place are under your control. 

Various physical, psychological, spiritual, and sociocultural factors are involved in the root cause of depression. Like anxiety, the effect is bidirectional: eating too much sugar and processed food, drinking alcohol to excess, and not exercising… they all lead to a greater risk of depression, and depression triggers a downward spiral of unhealthy lifestyle and behavioral choices and other chronic diseases. 

When I have a patient who tells me they feel run down, overwhelmed, or depressed, I inquire about the body’s inputs and outputs, starting first with food. Here are a few of the questions that I ask, whether you’re an executive or professional athlete, or stay-at-home mother.

  • “How many cups of vegetables are you eating each day?” I ask, because consuming more than five to eight servings is associated with happiness and better sleep, whereas caffeine and sugar are not. (In fact, more joy is an immediate benefit of eating more veggies!) 
  • “How’s your stress?” I probe about perceived stress because even if you don’t feel emotionally traumatized or acutely stressed, you could be depleting your stress reserves by not sleeping enough, overexercising and underrecovering, eating too many of the wrong carbohydrates or fats, skipping meals, or getting exposed to (known or unknown) toxins. Of course, we all know that not all stress is bad, but if your perceived stress is chronically elevated, it may be associated with leaky gut, dysbiosis, hormone imbalances, leaky brain, burnout, and depression. I know because I’ve been there in the past and have written five books about it.
  • “Do you have a history of trauma? What’s your ACE (Adverse Childhood Experiences) score?” The link between trauma and depression is strong,7 and is the subject of my next book. More soon.
  • “How’s your gut?” Did you know that you produce four hundred times more serotonin in the gut compared to the brain? And your gut makes other feel-good hormones like melatonin and estrogen (recall that estrogen is the master regulator of the female body)? Or that imbalances in your gut flora can cause altered thyroid function? So you can start to see how problems in the gut can be contributing to the symptoms of depression. The key is to look upstream of the depressed symptoms for the root cause—but first let’s see if depression is a problem for you. 

When it comes to the gut/brain axis and the link to depression, a good example is a toxin called lipopolysaccharide (LPS). When the microbiome is out of balance, this toxin from bad bacteria escapes into the bloodstream, causing brain fog and body-wide inflammation. If unaddressed, elevated levels of LPS can lead to inflammatory conditions like insulin resistance, weight gain, diabetes, obesity, and depression.  LPS toxicity is an important example of how the body’s response to a situation can lead to intoxication, in this case, autointoxication, also called LPS endotoxemia.

The problem with LPS was first recognized about one hundred years ago by a microbiologist who found that your own gut bacteria releases the endotoxin. That is, LPS is an endogenous toxin. The way it works is that LPS is naturally found on certain bacteria in the gut, and it stimulates a very strong immune response. This is good! When LPS gets in the wrong place, it causes profound inflammation in the body by triggering the immune system to activate on whatever it’s sticking to, leading to constipation and diarrhea, and then it exerts its negative effects on the brain, primarily through the microglia and by increasing the brain/body response to stress. This is bad. LPS in the blood can cause leaky gut, then leaky brain (by disrupting the blood-brain barrier), then neuroinflammation, leading to brain fog, and later, potentially depression, anxiety, and increased pain. Fortunately, there are ways to reduce LPS, including cutting back on saturated fat and eating more monounsaturated fat (which doesn’t raise LPS), and eating more prebiotic and probiotic food.

At a more sophisticated level, we think of a triad behind the root cause of depression. The triad is a risky combination of genetics, triggering event, and pathogenic intestinal permeability (so-called “leaky gut”). This means there’s not one specific brain problem associated with depression, but several biological, environmental, spiritual, psychological, and sociocultural factors that in combination put you at risk. I think about depression as the following triad (and BTW, this triad also applies to autoimmune disease).

  • You have a gene that makes you vulnerable to depression.
  • You encounter a trigger (a major stressor—say, a divorce or car crash, or other trauma).
  • Then you develop pathogenic intestinal permeability from environmental factors (examples: excess alcohol, excess stress, or glyphosate pokes holes in your gut wall, leading to leaky gut, and then inflammation).

While some people with depression have no family history or genetic predisposition to it, the triggers and environmental factors may be playing a larger role.

What are other environmental factors?

1. Air pollution
2. Lead
3. BPA
4. Smoking
5. Heavy alcohol use
6. Lack of social support
7. Lack of sleep
8. Low physical activity
9. Bad microbes, such as release of lipopolysaccharide (LPS) as indicated above

Case Study

Sonia (48) explained to me that the best thing for her brain fog was switching from a high-fat, very-low-carbohydrate, ketogenic-type diet to a whole-food, higher-carb, lower-fat diet with her carbs coming from fruit, vegetables, and tubers, like sweet potatoes, yams, or potatoes. She attributes her brain fog to a sluggish liver on keto and blood sugar problems. Maybe too much LPS in the wrong place was a problem for her, causing inflammation and weight gain. The excess fat was doing her brain a disservice, and there are reports in rodents of long-term adherence to a ketogenic diet being associated with worsening insulin resistance, hepatic inflammation, and fatty liver. She begins her day with a banana and celery juice, then has roasted vegetables like celery, carrots, and onions with some pastured turkey and avocado for lunch. She’s much better off than when she used to drink butter coffee and pastured hamburgers. I’m not suggesting that keto is bad, or that a higher-carb diet is right for everyone—I’m diet agnostic and don’t believe one size fits all—but Sonia is an example of someone who found the right fit for her through trial and error, and trial and success. She probably needs more carbohydrates for optimal thyroid and adrenal function. Your body is unique, and in the Brain Body Diet, you’ll find what works for you.

Brain-Body Protocol for Depression

Certainly, depression is a complex issue, involving food, stress triggers, genes, and environmental factors. Yet you actually have significant control over most of these factors.
When you take action to address them, you’ll address the root cause f depression and start to restore your joy, clarity, mood, and brain/heart connection. It’s not an easy task, especially if you are in a depression or if your brain is already overtaxed. That’s why social connections and help from others are so crucial to lifting yourself out of the dark. A supportive therapist, a kind friend, or an understanding relative can help encourage your gene expression to support a better mood.
Regarding the duration of the protocol: be guided by the severity of your symptoms as determined in the Interpretation section earlier in the chapter.

For people with mild depression, follow the protocol for forty days.
For moderate depression, perform the protocol for six to eight weeks.
For moderately severe to severe depression, see a clinician and do the protocol for eight to twelve weeks, or longer until symptoms resolve.
Here is the basic protocol – read Brain Body Diet, chapter 7, for additional details and the advanced protocol.

Step 1: Eat for joy.
What’s good for your mood? Consuming olive oil, fish, fruits, vegetables, nuts, legumes, poultry, and unprocessed, pastured meat—they are all associated with reduced depression risk and improved depression scores. Here are a few guidelines.

  • Eat according to traditional diets, such as the Mediterranean, Norwegian, Icelandic (lots of fresh fish), or Japanese.
  • Make sure you get your dark leafy greens or take a supplement for the B vitamins, such as methylfolate and P5P.
  • Consume more vegetables, nuts (just one serving per day), and seeds. Eat the rainbow.
    Make sure to get foods rich in omega-3 fats.
  • Avoid sugar, processed foods, fast foods, commercial baked goods, desserts, grains, alcohol, and caffeine. Repeat after me: sugar is a depressant. Eating it most days of the week, especially if you have insulin block, can trigger depression. It only takes three weeks for an addictive pattern to kick in and trigger cravings. Post-menopausal women may be at the greatest risk for the tie between sugar and depression.
  • Eat prebiotic foods, such as green bananas, potatoes, and crackers made from yuca.
    Taking probiotics decreases a depression score by 30 percent on average and works best on people under age sixty. Prefer to eat yogurt? That works too.

Step 2: Get bright light in the morning.
Sunlight (or bright light) works faster than prescription antidepressants to improve serotonin and mood, usually within one week, and with few side effects. Conversely, inadequate light in the morning is tied to circadian disruption and depression. So in this part of the protocol, I want you to get bright light from the sun or a specially designed light fixture for fifteen to sixty minutes a day. On a sunny day, the brightness is approximately 10,000 to 100,000 lux. On a cloudy, rainy, or snowy day, it may not be comfortable or possible to get the morning light that you need, so it’s helpful to have a high-intensity light box available at home.

Step 3: Practice yoga.
Yoga and meditation have been shown to correct the imbalance in the autonomic nervous system, lower cortisol and inflammation, and raise serotonin, sometimes in as little as ten days.
You can practice yoga in a way that reduces depression, and I highly recommend it along with the rest of the basic protocol for people with mild to moderate depression. I think of it as a great monotherapy when you feel depressed, as long as your score on the questionnaire earlier in this chapter is not in the severe range. (If it is, remember: see a clinician, and once your symptoms are improved, add yoga.) If you are already on an antidepressant, yoga can help. Infusing your body with fresh air with pranayama and, when warm, performing back bends and inversions are thought to be great remedies for depression. It’s always best to perform yoga with an experienced teacher watching your form and keeping you safe to reduce the risk of injury.


I once heard depression described as a response to perceived loss. That fits. If you struggle with depression, consider calling the new national crisis helpline by dialing 9-8-8. Given that most depression is linked to the gut/brain axis and inflammation, go on an anti-inflammatory diet, dive into exercise, and get the medical help you need. To read more, pick up my book, Brain Body Diet, and read chapter 7 where I dive into greater detail about how to reduce inflammation and reclaim your life.

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  4. Kuehner C. Why is depression more common among women than among men?. Lancet Psychiatry. 2017;4(2):146-158. doi:10.1016/S2215-0366(16)30263-2 (Note that additional citations are available in my book, Brain Body Diet, chapter 7)
  5. Bruce DG, Davis WA, Hunter ML, Peters KE, Davis TM, Starkstein SE. Lifetime depression history and depression risk in type 2 diabetes: A case-control study. J Diabetes Complications. 2016;30(1):38-42. doi:10.1016/j.jdiacomp.2015.10.010
  6. Shorey S, Ng ED, Wong CHJ. Global prevalence of depression and elevated depressive symptoms among adolescents: A systematic review and meta-analysis. Br J Clin Psychol. 2022;61(2):287-305. doi:10.1111/bjc.12333
  7. Chuong M, Adams MJ, Kwong ASF, Haley CS, Amador C, McIntosh AM. Genome-by-Trauma Exposure Interactions in Adults With Depression in the UK Biobank. JAMA Psychiatry. 2022;79(11):1110-1117. doi:10.1001/jamapsychiatry.2022.2983