8 Causes Behind Your Anxiety and Depression

Robin Berzin, MD
March 15, 2018

If you suffer from fatigue, anxiety, depression, or a combination of the three, you’ve probably been told by your doctor that it’s due to a chemical imbalance in your brain.

Many doctors jump to prescribe antidepressants, with 13 percent of Americans over the age of 12 reporting they took an antidepressant in the last month, according to the latest report from the National Center for Health Statistics. In some cases, antidepressants might be beneficial , but in other cases they may be masking the underlying cause of your symptoms.

Unfortunately, most doctors don’t dig deep enough to find out what may be the real cause. At Parsley Health , we use advanced testing to look at several variables that have been associated with anxiety, depression, and fatigue. Once we determine the root cause and develop a personalized treatment plan, we’re often able to reduce or eliminate the need for medications that treat these conditions.

8 overlooked causes behind fatigue, anxiety, and depression.

Ready to understand what’s causing your symptoms and start feeling your best? Ask your doctor about getting tested for certain nutritional deficiencies and imbalances. Here’s what could be at the root.

1. Your B12 levels are low.

Vitamin B12 is found in animal products, so vegans and vegetarians are most at risk for being deficient, as well as people with gastrointestinal issues, who may have difficulty absorbing the vitamin, and people on heartburn and reflux medications. The important vitamin is needed in order to make red blood cells and DNA and plays a major role in nerve function and mood. B12 helps to maintain the myelin sheath surrounding nerve cells, which make it possible for cells to communicate.

But when levels are low, this communication becomes compromised, which can lead to neurological changes. B12 is also involved in the production of serotonin and other neurotransmitters that regulate mood, so low levels could cause changes in the nervous system.

One study in the journal BMC Psychiatry followed 115 people with depression for six months and found that those with higher levels of B12 had a greater chance of recovery from depression, leading scientists to believe there is an association between B12 and mental health. Low levels of B12 have even been linked to decreased brain volume and cognition .

2. Thyroid issues are to blame.

Your thyroid gland produces hormones involved in metabolism and growth, releasing the hormones only when needed. But when your thyroid gets out of whack (from things like stress, diet, and environmental factors), your thyroid can overproduce or underproduce these hormones, leading to a range of physical and mental symptoms.

In a large 2015 study of people diagnosed with thyroid conditions, researchers linked an overactive thyroid (hyperthyroidism) to anxiety, while an underactive thyroid (hypothyroidism) was associated with depression. Another study found that 60 percent of patients with hypothyroidism reported symptoms of depression, while 63 percent reported symptoms of anxiety.

Researchers still aren’t exactly sure what underlying mechanism links thyroid disorders with depression and anxiety—there may be several —but the relationship between thyroid hormones and mood regulation is likely stronger than previously thought.

3. It’s in your gut.

The connection between your brain and gut isn’t just a one-way street (think: butterflies in your stomach when you feel anxious). A growing body of research is pointing to the bidirectional superhighway between your mind and stomach and its implication on mental health.

In one recent animal study , researchers discovered that levels of miRNA (molecules in the brain) were altered in mice raised without gut bacteria, as compared to normal mice. Prior research has suggested a link between anxiety-like behaviors and a change in miRNA, underscoring the importance of a healthy microbiome.

Another study in Psychosomatic Medicine of healthy women examined their gut bacteria composition and found that those with more of a certain bacteria group displayed higher levels of anxiety, stress, and irritability when they were shown certain negative images.

The research is still just scratching the surface, but one strong theory proposed by a scientist at Brown suggests that when the gut microbiota is unbalanced, the intestinal wall becomes permeable. This allows bacteria to pass into the bloodstream, increasing the risk for psychiatric disorders through several pathways. Cleaning up your diet and including probiotic-rich foods are key factors in good gut health.

4. You’re iron deficient.

Iron is essential in the production of hemoglobin, a protein that allows red blood cells to carry oxygen to your tissues and muscles. So when you have low levels of iron, less oxygen gets to your cells, keeping them from functioning properly and often leading to fatigue, weakness, and even anxiety and depression. Eventually, the lack of oxygen in your cells caused by this failure to produce enough hemoglobin can lead to anemia, a condition that can cause excessive fatigue, shortness of breath, dizziness, headaches, and more. But beyond physical symptoms, there may also be an association between low iron and anxiety, depression, or other mental health issues. A large 2020 study in BMC Psychiatry found that people with iron deficiency anemia had a significantly higher incidence and risk of anxiety disorders, depression, sleep disorder, and psychotic disorders.

More research is needed to understand the exact mechanisms behind this association, scientists point out, but we do have some clues. Iron deficiency has been found to affect neurological functioning and development, largely due to its role in many of the brain’s processes regulating mood, emotions, and psychological behaviors. The amount of iron in your brain is controlled by the blood-brain barrier, a collection of blood vessels that regulate the movement of ions, molecules, and cells between the blood and the brain in order to maintain homeostasis. This barrier tightly controls the amount of iron that’s able to pass through and enter the brain based on how much of the mineral is present in your body—so if your body is deficient in iron, the less iron that’s able to enter the brain. And since iron is an essential part of the systems and circuits in the brain that can dictate psychological behaviors, low iron levels in the body may make you more at risk for anxiety and depression. Research in the European Journal of Clinical Nutrition has shown that average ferritin level (a marker of stored iron) was significantly lower in depressed people.

Even though iron naturally occurs in the environment, iron deficiency is one of the most common nutrient deficiencies, affecting an estimated 25 percent of people worldwide . Women require more than double the amount of iron than men (and more during pregnancy), yet one out of every five women of childbearing age has iron-deficiency anemia, according to the National Heart, Lung, and Blood Institute . If you’re looking to increase your iron intake through your diet, iron-rich foods include grass-fed beef, chicken, and oysters. Since iron is most bioavailable in meat sources, if you eat plant-based it’s best to add some source of vitamin C (like lemon juice) to your plant source of iron (like spinach) to help with absorption.

At Parsley Health, testing for iron is part of the routine lab work recommended for every member. This provides the data needed to understand if there is a connection between your low iron and anxiety or depression. If you do have low iron levels, our doctors and health coaches will work with you to optimize your iron intake through your diet, helping you reach ferritin levels between 30-200ng/mL. If you’re not able to reach optimal levels through diet alone, your doctor may prescribe an iron supplement and will work with you to resolve any underlying causes that could lead to iron deficiency, like a hormonal imbalance or a gut issue.

5. You’re lacking in Vitamin D.

If you’ve got a job that keeps you indoors most of the day, chances are you may be part of the 42 percent of Americans with a vitamin D deficiency. Vitamin D is created by your body when sunlight hits the skin and is found in fatty fishes like salmon and tuna, eggs, and mushrooms.

Most people associate low vitamin D with wintertime and seasonal depression, but it can hit at any time of year. A thorough review of studies analyzing depression and vitamin D concluded that lower vitamin D levels were found in people with depression compared to controls.

Scientists also found that when depressed individuals received vitamin D supplementation for one year, they had significant improvements in symptoms of depression compared with depressed people taking a placebo. The area of the brain associated with depression is also a site of vitamin D receptors, posing one possible explanation for the link between the two.

6. You have unstable blood sugar.

You don’t have to be diabetic to have a blood sugar problem. We help many of our patients here at Parsley Health pull the brakes on the rollercoaster of symptoms they’ve been experiencing from spikes and dips in blood sugar.

Take a typical on-the-go breakfast for many people: a pastry and sugary coffee drink. That wave of sugar creates a rapid spike in your blood sugar and causes your pancreas to release insulin to stabilize it. As your blood sugar returns to normal, you crash, feeling tired. You’ll also feel hungry again pretty quickly, leading you to reach for carbs and perpetuating the cycle.

All that sugar adds up. When people consumed 40g of added sugar a day in the form of a can of soda for three weeks, they showed at least a 60 percent increase in high-sensitivity C-reactive protein , a marker for inflammation . Inflammation has been associated with many chronic diseases, including depression. Learning to eat a combination of fiber, protein, and healthy fat at each meal and never skipping a meal can help you maintain steady blood sugar throughout the day and tame inflammation.

7. You drink alcohol in excess.

You might think happy hour is the ultimate way to unwind from your day, but the temporary effects of alcohol are just that—temporary. When you drink, alcohol increases dopamine, a feel-good chemical, and binds to and alters the neurotransmitter receptor GABA, which increases the effect of GABA and can have a calming effect in the moment. But it also interrupts other mood-regulating neurotransmitters, like serotonin. When these alcohol-induced effects wear off, you may experience a range of anxiety symptoms.

In the long term, excessive drinking makes neurons less excitable and permanently changes the mRNA and protein levels in GABA receptors. This makes the receptors less sensitive, so the brain needs more GABA. Without it, symptoms of anxiety can result. This doesn’t necessarily mean you have to completely remove alcohol from your life, but take at least three nights off per week from drinking and always drink in moderation.

8. It’s in your genes.

Everything else aside, you could be the picture-perfect vision of health but still struggle with depression. A study of 460,000 people in Nature Genetics used data from 23andMe to discover 15 regions on the human genome associated with risk of major depression. These areas represent irregularities that people with reported depression had when compared to people who did not report depression.

One such gene mutation that’s been widely studied is methylenetetrahydrofolate reductase (MTHFR). MTHFR produces an essential enzyme that converts folate into an accessible form which plays a role in mood-regulating neurotransmitter production. Research has found an association between a MTHFR mutation and depression and other mental health disorders.

In some cases, scientists believe it may be possible to use folate as a treatment option for MTHFR-associated depression and anxiety. Another gene, NKPD1, was also recently linked to depressive symptoms . Researchers think it may account for up to four percent of the heritable risk for depression.

Robin Berzin, MD

Dr. Robin Berzin is the Founder and CEO of Parsley Health, America's leading holistic medical practice designed to help women overcome chronic conditions. She founded Parsley to address the rising tide of chronic disease in America through personalized holistic medicine that puts food, lifestyle, and proactive diagnostic testing on the prescription pad next to medications. Since founding Parsley in 2016, Dr. Berzin has seen 80% of patients improve or resolve their chronic conditions within their first year of care, demonstrating the life-changing value of making modern holistic medicine accessible to everyone, anywhere. Parsley is available online nationwide.

Dr. Berzin attended medical school at Columbia University and trained in Internal Medicine at Mount Sinai Hospital in New York City. Her book, Prescription for Happiness: How to Eat, Move, and Supplement for Peak Mental Health, was published by Simon Element in January 2022.

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