The Vicious Cycle of Depression And Obesity
One person climbs the steps to do some exercise in a rehabilitation center in Tahiti.
Since 1975, the worldwide obesity rates have nearly tripled. At the same time, rates of depression have steadily risen. Since the early 2000s, many studies have established a link between these two conditions, showing that the prevalence of depression in people with obesity is twice as high as in people of a healthy weight.
Elina Hypponen (director of the Australian Centre for Precision Health) at the University of South Australia in Adelaide says that intuition is a part of this association. According to Hypponen, obesity is viewed as a stigmatized condition that can affect their mental health. The two conditions are also influenced by some of the same risk factors - including less-healthy eating habits, physical inactivity, disrupted sleeping patterns and substance abuse.
But in truth, the relationship between obesity and depression is much more complicated. Over the last decade, research has shown that obesity and depression are intertwined with biochemical interactions. Each condition conspires to worsen the other.
A Double Dose Of Inflammation
Chronic inflammation is common in obese people. A variety of immune cells reside in fat tissues, and these signalling proteins are associated with chronic inflammation. Overproduction of such molecules is common in obese people. Some of these proteins, such as cytokines, are so closely related to mental-health problems that they're commonly used as biomarkers for depression1.
Many studies have shown that cytokines are able to downregulate the levels of serotonin (a vital hormone in mood regulation). By stimulating an enzyme, cytokines alter the amount of amino acids required to make serotonin.
The cytokine effect provides one biological explanation for why people with obesity are at greater risk of developing depression, but it cuts both ways (see 'Vicious cycles'). Study after study has shown that those who suffer from depression, regardless of how their body looks, have higher levels of cytokines.
Insulin resistance can develop from pro-inflammatory cytokines, which may lead to type 2 diabetes. And, because people with this type of diabetes have an increased risk of gaining weight, it's therefore equally possible that elevated cytokine levels caused by depression are contributing to obesity. Hubertus Himmerich is a London psychiatrist.
Stephanie Borgland is a Canadian neuroscientist who echoes this analysis. "Individuals with obesity and depression show increases in pro-inflammatory cytokines," she says. It's difficult to pinpoint which conditions is to blame.
The Stress Connection
The stress hormone cortisol, also known as cortisol, is created in situations that are potentially dangerous or demanding. Cortisol causes blood sugar to rise and supplies the brain with glucose. Cortisol is helpful in short-term situations. Studies have found that stress biochemical conditions such as depression may lead to a prolonged period of anxiety .
For two weeks, researchers observed 41 Macaque monkeys (Macaca Mulatta) over a period of one hour each day for 2 weeks. The researchers looked out for behaviour such as bowing the head or curling up into the fetal position, which were deemed to be potential indicators of depression. The scientists also obtained hair samples to determine cortisol levels. 18 of the monkeys did not show signs of depression and were therefore treated the same as the control group. End results revealed that depressed monkeys of 23 produced significantly higher levels cortisol than control monkeys.
Similar results were also observed in humans. Researchers assessed the mental well-being of 89 men in a paper published in 2019. They also took blood samples for cortisol measurement. They found a positive correlation between cortisol levels and depression3.
This represents another key link between obesity and depression, says psychiatry researcher Valerie Taylor, who collaborates with Borgland at the University of Calgary, because cortisol has many roles beyond stress response - one of which is to increase appetite. Taylor says that high levels of cortisol can lead to weight gain. It has a self-soothing component. This is why chocolate ice cream can be a good choice for someone who has broken up with you. Depression can mean a continuation of this."
So, if depression increases cortisol, it stands to reason that obesity could be a knock-on effect. However, cortisol effects can also flow in opposite directions, just as with cytokines. Obesity, independent of depression, is also correlated with high cortisol concentrations. A meta-analysis that looked at obesity, but not depression, found that for every 2.5-point increase in body mass index, there's a corresponding 9.8% increase in cortisol found in hair samples4. High cortisol - linked to depression - can fuel obesity. And high cortisol - linked to obesity - can also end up intensifying depression. With each new turn, the cycle becomes more intense.
"Obesity and depression are bidirectional and multifactorial, so it's really hard to unpick," says Richard Morriss, a clinical psychiatrist and researcher at the University of Nottingham, UK. "The real kick in the teeth for someone who is both obese and depressed is that depression is fundamentally characterized by a loss in motivation, but to tackle obesity you need that motivation to eat better and exercise."
Ask Questions About Treatment
This is as confusing to comprehend for the treatment. For starters, Morriss says awareness of the link between obesity and depression is low. He thinks obesity deserves to be treated with the same seriousness as anorexia . According to him, being overweight is a serious mental-health issue. But if you are too obese, then it is still considered a health problem.
Morriss states that people suffering from depression and obesity often receive treatment separately. "The psychological treatment for depression often ignores the obesity factor," he says. Inadvertently, intervening in one condition may have adverse consequences for the others. Both should be monitored closely.
Weight gain can be a side effect for almost all antidepressants . "You take the medication to reduce depression, but it causes you to gain weight which worsens your depression, so you take more antidepressants, and so it goes on," says Taylor.
Antidepressant users who are obese should not be concerned about gaining weight. In a 2021 study, Morriss and his colleagues investigated the medical records of more than 32,000 adults with obesity who also had depression. People who took antidepressants were at greater risk for complications such as diabetes or cardiovascular disease. Although it is not clear why this trend exists, Morriss worries. Morriss says that after 12 months of antidepressant use, people need to be evaluated. "We are trying to dissuade the notion that people should stay on antidepressants for life." Similar results have been found in other studies regarding antidepressant usage in general population6.
This is not to suggest that antidepressants should be ignored. In fact, Taylor recommends prioritizing depression over obesity. "You have to treat the depression first because you can't make significant lifestyle changes until you're mentally well," she says. She says, "You cannot lose weight if you are actively depressed." However, doctors who wish to address the issue holistically must consider possible adverse effects of antidepressants on obese patients.
The obesity aspect of the problem is not an easy one. In 2021, Himmerich and his colleagues conducted a systematic review of 24 studies that looked at obesity and depression7. This enabled the researchers to access data from more than 3,200 people with an aim of working out whether weight loss through dieting had the added bonus of also alleviating depression.
There's been a lot of debate about what kind of diet is best to help lift people out of depression, says Himmerich. The key questions are whether it would be best to concentrate on weight loss or whether supplementation with vitamins, omega-3 fatty acids, and other nutrients might prove beneficial. Himmerich admits there is no clear answer. He says, "The science of depression is complex because so many studies contradict each other." "But our systematic review showed that calorie-restricted diets can decrease people's depression score."
For those who have lost too much weight, there's a catch. Himmerich states that many people gain weight very quickly following a strict diet and may end up becoming worse off than before. There needs to be a maintenance period where individuals can be guided and instructed.
Sadly, this kind of tailored therapy doesn't exist for the vast majority of people with obesity and depression. Morriss says that patients can't find anyone who will take them on the whole journey. The combined problem of obesity and depression is unlikely to improve , he says, until therapeutic techniques evolve to confront and manage both problems.