In this video, Vladimir Maletic, MD, MS, discusses diet and nutrition challenges that patients with major depressive disorder may be experiencing during the COVID-19 pandemic. Dr. Maletic is a member of the Psych Congress Steering Committee and Clinical Professor of Psychiatry and Behavioral Science, University of South Carolina, Greenville.
Read the transcript:
Hello. My name is Vladimir Maletic. I am Clinical Professor of Psychiatry and Behavioral Science at University of South Carolina in Greenville, South Carolina. The topic of our conversation this morning will be the influence of COVID‑19 on dietary requirements in major depressive disorder.
One might ask, "Is this a topic that deserves some special attention at this point? Is there anything that would be specific to COVID‑19 and nutrition in depressed patients?" I would say definitely so.
COVID‑19 pandemic may have had direct and indirect impact on the risk of depressive relapse. When it comes to indirect impact, there's a lot of stress in lives of patients suffering from major depressive disorder during these times related to compromised social supports, changes in circadian rhythm. People are going to sleep at odd times, napping during the day. Very often, there is increased substance use. There is also, unfortunately, in part due to change in daily schedule, possibly in part because some of the reminders are lacking, decreased treatment adherence.
In addition to that, many patients who have major depressive disorder receive psychosocial treatments. Many of the outpatient clinics either have limited hours or have closed. I've had several depressed patients report to me that they can no longer see their therapists with regularity.
Unfortunately, due to a lack of support from other mental health professionals and limited access to general health clinics, unless one is in an urgent situation, there are problems. All of these factors influence risk of major depressive disorder.
In addition to that, patients suffering from major depressive disorder are not exercising as much, which is quite understandable. Many of the gyms are closed. Due to the change in routine, they are not exercising as regularly as previously and are frankly making some poor dietary choices.
Instead of adhering to their usual diet, very often they're up in the middle of the night, and they're making trips to fast food restaurants in the middle of the night. All of that has resulted in increased risk of destabilizing mood and precipitating depressive episodes.
Having increased stress due to some of the reasons that have been mentioned, we can add to that distance from friends and family members and financial stress related to COVID‑19. Many times, it's unemployment situation.
There is typical stress response. Hypothalamic‑pituitary‑adrenal axis tends to be overly active. Increased cortisol and other hormones, which obviously have an impact on metabolism. In addition to that, there is a disbalance in autonomic activity, more sympathetic activity, less parasympathetic activity, as well as increased inflammatory signaling.
Whenever one is under distress, food choices change. I don't think you have heard people saying, "Oh, I'm stressed out. I can hardly wait to get home and get into my celery sticks and carrots." It's usually cream pies and ice creams. When one is under duress, one tends to seek out so‑called comforting foods, or comfort food, which tend to be calorie‑dense foods.
What would be direct impact of COVID‑19? COVID‑19 has been associated with so‑called cytokine storm. Cytokine storm is increased peripheral inflammatory signaling. These inflammatory signals do reach the brain. Once they reach the brain, they cause perturbations of neurotransmission, so monoamine signaling is off. Norepinephrine, dopamine, and serotonin, as well as changes in GABA and glutamate transmission.
Increased peripheral inflammatory signaling also translates into diminished neuroplasticity. All of these events compromise appropriate activity of circuitry that is involved in regulating mood, and therefore carry increased risk of major depressive disorder relapse.
What are some of the nutritional adaptations that one can make? They have to do both with quantity and quality of food. Speaking about quantity of food, we know that there is genetic link between major depressive disorder and risk for obesity. These 2 conditions, based on large, genome‑wide association studies, share anywhere between 15 to 20 common risk genes. There is a genetic setup, and some individuals—not all individuals suffering from depression, but some individuals suffering from depression—actually have different response to food than typical individuals.
How is this different? Based on imaging studies, it has been demonstrated that their reward circuitry has overly intense response to calorie‑rich foods. It is sometimes almost irresistible temptation.
It tends to be present more in individuals who suffer from so‑called atypical depression, where it is also associated with, in addition to increased appetite and food intake, it is associated with decreased energy and psychomotor retardation.
These individuals tend to have altered signaling between adipose tissue and the brain. If we have accumulated too much adipose tissue, it will start releasing typically leptin and adiponectin.
Individuals who have atypical depression have been demonstrated to have elevated levels of leptin, but decreased leptin receptor sensitivity. Meaning that their brain is not receiving the message that they have overabundance of calories stored.
On the other hand, adiponectin is an intermediary compound involved in regulation between adiposity—so accumulation of fat tissue—inflammatory signaling and sensitivity of insulin receptors.
In other words, patients who have depression on average will have decreased levels of adiponectin, meaning that they are at a greater risk of developing metabolic disorders. Presence of adiposity does not signal to their brain and does not make adjustment in sensitivity of insulin receptors.
All of this can be problematic as increase in appetite and adiposity increase the risk of having depressive episode. Vice‑versa, having depression increases the risk of obesity.
What can we do in terms of our dietary recommendations? A couple of things. One is limit the amount of dietary intake to balance out caloric requirements and exercise levels. The concern is if the BMI continues to grow, increased BMI has also been associated with decreased response to antidepressants. It becomes a vicious cycle.
Are there some specific diets that can be helpful in these circumstances? Definitely so. Studies have shown that modified Mediterranean diet, so‑called anti‑inflammatory diet, may be of benefit in individuals who suffer from major depressive disorder.
What are some of the main points of this modified Mediterranean diet? The emphasis is on fresh vegetables, especially green leafy vegetables and legume, as well as fresh fruit, especially berries, which seem to have greater antioxidant content.
Furthermore, ingesting more nuts, seeds, and whole‑grain cereal seems to be beneficial. In terms of protein, fish is definitely preferred. It appears that poultry and white meats may be relatively neutral. Moderate consumption of coffee and tea; alcohol no more than one glass of wine a day.
It is suggested that cooking with olive oil would be preferential. What do these individuals need to avoid? They need to avoid red, processed meat, fast food, fried food, sweetened beverages, simple sugars, and excessive alcohol intake.
What might be some of the payoff, some of the benefits from this modified Mediterranean diet? Modified Mediterranean diet is associated with decreased risk, not only of variety of chronic mental health problems, but also medical problems.
This is a huge bonus, because having chronic medical illness, along with stress, is one of the major precipitants of future depressive episodes. If one adheres to Mediterranean diet, one will have reduction in obesity. One will have reduction in inflammatory signaling. There will be improvement in cognition. In addition to that, imaging studies have found that there is an increase in total brain volume. This applies both to gray and white matter, as well as improved brain connectivity.
In other words, circuitry that is involved in regulation of stress response and mood is likely to function better if one has proper diet. Are there any indicators in the studies that support this? Indeed, patients who adhere more to this modified Mediterranean diet have reported greater life satisfaction, have higher wellness scores and happiness scores.
Indeed, what we eat does influence our mood to a significant degree. There is a specific scenario related to major depressive disorder when it comes to gut‑brain signaling. Namely, a number of patients who suffer from major depressive disorder also has something that is termed gut dysbiosis.
This refers to altered composition of gut flora. Altered composition of gut flora has significant ramifications. Not only is the gut the greatest immune organ and endocrine—so about 70 to 80 percent of immune cells reside in the gut—it is a major source of serotonin, dopamine.
Anywhere between 80 and 90 percent of serotonin is synthesized in the gut. About 50 percent of dopamine is synthesized in the gut. Gut also has a significant role in producing glutamate and GABA.
If gut‑brain axis is not functioning very well, it may very well have impact on neurotransmission in the brain. You have probably heard reference to “leaky gut.” Leaky gut allows exposure to various antigens and increased inflammatory signaling.
This increased inflammatory signaling does come to the brain. We have already mentioned that there is relatively constant relationship between peripheral and central inflammation, whereby central inflammation may cause perturbation in neurotransmission, in neuroplasticity, and the function of the brain circuitry involved in mood regulation.
Can anything be done to correct this? Yes, there is evidence that probiotic use—when I say probiotic, these are live microorganisms that are ingested—they can help with mood. What are some of these bacteria that can be obtained in health food stores in various probiotic preparations?
Typically, they include lactobacillus and bifidobacter. A typical amount would be two billion culture‑forming units per gram. Use of these probiotics in controlled studies has been associated with reduction in depression scores compared to controls and placebo‑treated individuals.
A more recent development, I'm talking about research conducted in the last couple of years, indicates that symbiotics may be even better. What are symbiotics? Those are pro[biotics] and prebiotics combined. A combination of pro[biotics] and prebiotics may have been even more effective in improving depressive symptomatology as well as decreasing inflammatory signaling and promoting neuroplasticity.
What are some of these prebiotics, and what is the relevance of prebiotics? Again, probiotics are live cultures. Prebiotic is nutrition for these live cultures. They include nondigestible carbohydrates. They can be found in various sources of dietary fiber, such as onion, garlic, apple, bananas, artichokes, asparagus. All of this will support healthy gut flora.
In addition to pre[biotic] and probiotic, are there any other kind of nutrition supplements that can be helpful in depression? I must preface this by saying that data and evidence is uneven when it comes to use of some of these micronutrients.
Be it as it may, there's pretty solid proof that vitamin B complex, including folate and L‑methylfolate, may be helpful in depressed individuals, especially in situations where there is higher body‑mass index, higher inflammation, or higher oxidative stress.
S‑adenosyl‑L‑methionine, or SAM, also has some evidence supporting its efficacy, as does N‑acetylcysteine, often referred to as NAC. Acetyl‑L‑carnitine has some interesting research that has been conducted recently indicating that it may help with metabolic status and mood in individuals who have propensity towards depression. There are also control studies supporting the use of saffron and curcumin in individuals suffering from major depressive disorder.
Especially in COVID‑19 pandemic times, individuals don't leave their home a whole lot, and therefore have less exposure to sun. There is some indication that decreased vitamin D levels may be supportive of developing depressive symptomatology. Unfortunately, there is much less evidence suggesting that correction of vitamin D is helpful with depression. Nevertheless, it's a good idea to at least have normal, healthy levels.
In addition to that, there is some evidence that some of the microminerals may be helpful. I'm speaking about calcium, zinc, magnesium, and selenium.
Particularly, if the levels of these microelements are decreased, supplementation may be useful. Finally, there is some limited support that DHEA (dehydroepiandrosterone) may also be supportive of good mood.
In summary, COVID times have created great disturbance and distress in our patients' lives. Indirect impact of stress leads to disturbance in HPA axis, autonomic regulation, and inflammatory tone, which can act as precipitant to depressive episodes.
Having correct nutrition, adhering to modified Mediterranean diet, having greater intake of pre[biotics] and probiotics, as well as some of these nutraceuticals may help ward off the risk of major depressive episodes in these circumstances.
With that, I would like to thank you on your kind participation in this program. I hope that some of this information will be of use to you and your patients, and I wish you to stay healthy and well. Thank you.