crystal ball
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What your uric acid level is trying to tell you about your depression.

Is It Depression or Bipolar Disorder?

This is one of the most challenging questions psychiatrists face in daily practice, and getting the answer wrong can have serious consequences.

Both major depressive disorder and bipolar disorder can involve bouts of severe depression that interfere with one's ability to function, but manic episodes only occur in bipolar disorder. While most people think of manic episodes as periods of extreme excitement, euphoria and hyperactivity, mania can take other forms, such as irritability, rage, intense anxiety, prolonged panic, or extreme obsessive-compulsive symptoms.

It can be surprisingly difficult sometimes even for experienced clinicians to tell the difference between major depression and bipolar disorder because most people seek care during a depressive episode, and depression symptoms can look similar in both cases. Mood patterns over time and family history of bipolar symptoms can offer clues that help distinguish between the two disorders, but the diagnostic process remains an inexact science - particularly early in life before clear patterns become obvious, or in people who have severe anxiety instead of classic manic symptoms.

Getting the diagnosis right is important - partly because it helps people understand their condition and have a better idea of what to expect, and partly because the medicines used to treat major depression (antidepressants) and bipolar disorder (mood stabilizers) are usually very different. Prescribing a typical antidepressant like Zoloft (sertraline) instead of a mood stabilizer like Lamictal (lamotrigine) to someone with unrecognized bipolar disorder could potentially cause a manic episode, worsen depression, or even trigger serious suicidal thoughts or behaviors.

A test that could help with diagnostic and treatment decisions would certainly be a big step in the right direction.

The Uric Acid Test

Researchers at the University of Coimbra in Portugal may have found a simple new way to help predict which people with depression will later go on to develop bipolar disorder: a blood test for uric acid.

Uric acid is a by-product of purine breakdown. Purines are essential building blocks of DNA (genes), RNA (protein manufacturing messengers) and ATP (energy storage particles) - all centrally important to the inner workings of our cells. Whenever a cell needs to dispose of old purine molecules, it turns them into uric acid and releases that uric acid into the bloodstream. In healthy people, the kidneys remove some of the uric acid from the body through urination and leave just the right amount in the bloodstream for the body's needs. It is normal to have some uric acid in your blood at all times, but too much uric acid can signal trouble.

The uric acid test is nothing new - it has been used for many years to monitor people with gout, who sometimes have too much uric acid in their blood. You can request the test from your health care provider; it is inexpensive and usually covered by insurance.

So, what does any of this have to do with the brain?

Uric Acid and Bipolar Disorder

In this new study, scientists observed that people hospitalized with major depressive disorder who also happened to have higher levels of uric acid in their blood were more likely to be diagnosed with bipolar disorder in the next eight to eleven years.

How much more likely?

A remarkable 48% of people (53 out of 111) with high uric acid levels went on to develop bipolar disorder, whereas only 1.4% of people (two out of 139) with low uric acid levels went on to develop bipolar disorder.

That is a very big difference.

This observation suggests that if you have depression, and your uric acid levels are too high, you are 34 times more likely to go on to develop bipolar disorder in the coming years than if your uric acid levels are low.

How High Is Too High?

In men, uric acid levels higher than 5.35 mg/dL (or 318 micromoles/liter) were associated with increased risk for bipolar disorder.

In women, uric acid levels higher than 4 mg/dL (or 357 micromoles/liter) were associated with increased risk for bipolar disorder.

Interestingly, these higher levels are considered to be in the "normal" range simply because they are well below the levels typically associated with gout (people with gout tend to have uric acid levels above 6.8 mg/dL).

What Does this Study Mean about Mood Disorders?

For too long, most scientists have thought of mental health and physical health as separate areas of research, even though studies have conclusively shown that the head is part of the body...

Researchers know very little about what causes mood disorders, so innovative studies like this one, which explore the potential relationship between general metabolic health and psychiatric conditions, are exciting and raise fascinating, important questions about the very nature of mood disorders.
  • Are major depressive disorder and bipolar disorder really two distinct conditions, or do underlying metabolic problems cause major depressive disorder to slowly "morph" into bipolar disorder over time?
  • Does excess uric acid play a direct role in triggering bipolar symptoms? The authors mention that uric acid levels affect the activity of a neurotransmitter in the brain called adenosine, which helps regulate how excitable brain cells are; perhaps this may help to explain the association. More importantly, adding allopurinol (a medicine that lowers uric acid levels) to mood stabilizing medications helps ease manic symptoms better than mood stabilizers alone, suggesting that uric acid may at least influence the severity of the disorder.
  • Is bipolar disorder inevitable, or potentially preventable? If you have severe depression and your uric acid is above the cutoff level, your chances of developing manic symptoms of bipolar disorder in the coming decade or so are about 50/50. Essentially, a uric acid test is like a crystal ball, offering you a glimpse into your emotional future. If you dare to gaze into it and find out that you are in the high-risk category, what are you supposed to do about it?
The authors of this new study suggest that this test can help guide your clinician in the decision about what kind of medication to prescribe for you. As a nutrition-oriented psychiatrist interested in root causes of mental illness and dedicated to minimizing the use of medications, I view the uric acid test as more than a simple prescribing tool; I see it first and foremost as a window into your metabolism that can inspire and empower you to REDUCE your risk for bipolar disorder.

The key lies in understanding what is causing your uric acid level to rise in the first place.

What Causes High Uric Acid Levels?

The most common culprits known to raise uric acid levels are:
  • Alcohol
  • Certain medications, including low-dose aspirin, diuretics, vitamin B3 (niacin) supplements, some chemotherapy drugs, and some immune suppressing drugs
  • Xylitol and sorbitol (sugar alcohols used as sweeteners)
  • High blood insulin levels
It's been known for a long time how important it is to limit alcohol use and review your medication list with your health care providers if you have high uric acid.

The old thinking was that meat was a major contributor to high uric acid levels (because it is high in purines), but this theory was grounded in guesswork, and has not held up to scientific testing. [To learn more, read my article "Got Gout but Love Meat?" and "Is Gout Caused by Red Meat or Metabolic Syndrome?" by nutrition specialist Amy Berger.]

The new kid on the block, and the most common root cause of high uric acid, is high insulin levels - sometimes also called "insulin resistance" or "pre-diabetes." Insulin resistance now affects more than 50% of all Americans, and has reached epidemic proportions around the world, including in Portugal, where this study was conducted. High insulin levels tell the kidneys to reduce the amount of uric acid they release into the urine, allowing more uric acid to remain behind in the bloodstream.

Insulin resistance is one of the signs of "metabolic syndrome" - a cluster of health problems including high blood pressure, high triglycerides and weight gain that can eventually lead to type 2 diabetes, heart attacks, and even Alzheimer's disease. It is well-established that metabolic syndrome and high uric acid levels often go hand-in-hand. Essentially, rising uric acid levels represent a clue that the inner workings of your metabolism are in distress, placing your physical and mental health at risk.

In this interesting study, people with bipolar disorder who also happened to have insulin resistance were more likely to experience rapid cycling and less likely to improve in response to the mood stabilizer Lithium, suggesting that insulin resistance may contribute to the severity of bipolar symptoms.

How to Lower Uric Acid Naturally

You could take a medicine that lowers uric acid levels, but the way to get to the root of the problem, without co-pays or side effects, is by changing your diet.

The single most powerful trigger for high insulin levels is refined carbohydrate - rapidly-digestible simple sugars and starches like flours, fruit juice, processed cereal products, and sugars. Avoiding these modern ingredients is a logical and healthy first step that makes sense for all of us, whether we have depression or not. However, if your metabolism is more badly damaged, simply avoiding the refined carbohydrates may not be enough. You may want to consider a low-carbohydrate diet that also limits whole food sources of carbohydrates (whole grains, legumes, fruits, and starchy vegetables). Other strategies that can help lower insulin levels and improve insulin resistance include very low-calorie diets, intermittent fasting, and strength training.

There are no studies yet demonstrating that lowering insulin levels reduces risk for bipolar disorder, but there are plenty of studies demonstrating that lowering insulin levels, eating a healthier diet, and getting some exercise improve your overall physical and mental health, so what have you got to lose?

Georgia Ede, MD, is a Harvard-trained psychiatrist and nutrition consultant practicing at Smith College. She writes about food and health on her website DiagnosisDiet.com.