IIf you’ve paid attention to the science of mental health, you’ve probably heard the theory that depression is caused by a chemical imbalance in the brain. Since the 1990s, the common symptoms of low mood, loss of interest and pleasure, changes in sleep and appetite have been said to arise from a lack of a neurotransmitter called serotonin. By increasing levels of this happiness hormone, certain antidepressant pills, such as Prozac, could alleviate our inner torment and restore equanimity to our minds.
The truth, as always, turned out to be more complicated. Last year, an influential analysis of available data concluded that there was no clear evidence to support the theory, and the headlines that followed left many perplexed about who or what to believe.
Two new books can help us cut through the confusion. The first, Overcoming Depression, comes from Philip Gold, a senior investigator at the US National Institute of Mental Health who has spent a lifetime investigating the disease. Gold performed some of the first trials of the first antidepressants and continues to work on the cutting edge today.
Many sections of Overcoming Depression Read like a medical memoir, interspersing stories from the front lines of this research with detailed scientific explanations. I found his descriptions of the condition painfully accurate. Gold rejects the common idea that depression is medicalized sadness, noting that true sadness is often associated with fond, loving memories of, for example, a lost loved one, combined with sadness over their loss and, sometimes, a bittersweet feeling that encompasses both. the blessings of life and the harsh reality that all relationships must come to an end. Such feelings, he says, are typically not available to severely depressed individuals, whose emotional repertoire is restricted to a deadly litany of self-exaltation and hopelessness.
The condition is often accompanied by physiological changes, leading Gold to call it a full-body disease. He notes that it is associated with premature coronary artery disease, diabetes, stroke and osteoporosis, an under-recognized burden for the one in five people who develop depression. On average, depression shaves about 10 years off someone’s life expectancy. It is, Gold concludes, a cancer of the self that erodes our dignity and self-respect, even as it erodes our bodies.
Gold argues that many cases of depression result from a stress response gone wrong. When a healthy person faces a dangerous situation like a wildfire, point out that it makes sense to focus on the threat itself and how to deal with the immediate risk until they find safety. The brain begins to prepare the body for action, which includes increasing inflammation and blood clotting to reduce the risk of infection and bleeding after an injury.
For many people with depression, however, the brain’s alarm bells continue to ring long after a real threat has passed. Continues to look for potential signs of danger or hostility, ignoring things that could bring rewards. As Gold writes, it’s one thing to maintain singular focus when there’s a wildfire nearby, but in normal life the inability to appreciate any pleasurable stimulus is a great burden. This results in the profound dread and lack of pleasure and motivation that characterize the disease, and seriously disrupts normal eating and sleeping routines. Living in a state of permanent stress can result in the death of brain cells and a reduced ability to form new neural networks, leaving a person trapped in their destructive thoughts. For this reason, Gold describes depression as a neurodegenerative disease and states that any effective treatment will need to undo this damage and prevent it from occurring again.
Gold presents a convincing argument for his theory, but Camilla Nords The Balanced Brain offers many alternative points of view. Nord leads the Mental Health Neuroscience Laboratory at the University of Cambridge, and his writing is masterfully nuanced on the treatment of depression without sacrificing the clarity of his argument. All the while, she is careful to explain how experiences can vary widely from person to person. Rather than opting for a simplistic narrative, she recognizes the ambiguities in academic research into mental illness.
There has been a lot of excitement about the potential role of bodily inflammation as a potential cause of depression rather than a consequence. But only a subset of patients have above-average inflammation, while others have normal levels. And even among those with intense inflammation, the underlying source can be found in different parts of the immune system. Targeting the immune system could represent a new avenue for treating or improving mental health, but it would require carefully finding the right immune targets and tailoring treatments to each individual based on their specific immune system, Nord writes.
The cognitive causes of depression can be equally varied. A convincing explanation of depression concerns the basic ways in which the brain learns from its experiences and predicts the future, but the exact nature of the problem varies from patient to patient. Some people’s brains can place too much emphasis on negative outcomes; another person’s brain may not be able to predict potential rewards. Either way, the overall result can be a more pessimistic and frightening view of the world, which disorganizes someone’s life.
For some commentators, the recent collapse of the chemical imbalance theory has cast doubt on the use of existing antidepressant medications, which were intended to restore lost serotonin. However, the data certainly suggests that they work better than placebos and the authors of these two new books can explain why. For Nord, it’s because antidepressant medications help correct fundamental biases in someone’s perception of the world. This change occurs incredibly quickly. People with depression are more likely to see anger and less likely to see happiness in neutral facial expressions, but in many patients this tendency begins to disappear after taking just one antidepressant pill. Gold, meanwhile, points to studies that show that our current antidepressant pills stimulate the birth of new brain cells and neural connections, which would help people break free from the overactive stress response.
The same applies to the new generation of treatments, such as the psychedelic drug psilocybin, which has recently shown great promise in clinical trials and can bring great relief after a single dose. Nord suggests that opening the doors of perception can help reset the brain’s predictions, immediately snapping someone out of their bleak worldview. For Gold, it’s about restoring connectivity between different regions of the brain and undoing neurological damage; He points to studies showing that psilocybin binds to the same receptors as brain-derived neurotrophic factor, a protein that promotes the growth and rewiring of neurons. Perhaps both explanations are correct or they are simply different ways of expressing the same experience. The most interesting thing is that the drug appears to work well for many people, with apparently few unwanted side effects.
Nord and Gold suggest a constellation of promising treatment options, including other psychedelic drugs and various forms of brain stimulation. Through brain imaging and genetic testing, it may even be possible to predict which treatments will work best for each person. Without offering false hope, both books are ultimately optimistic about our future understanding of depression. The chemical imbalance theory may have been defunct, but there are now many more flashes of light in the darkness.
David Robson is an award-winning science writer and author of The Expectation Effect: How Your Mindset Can Transform Your Life
Overcoming Depression: New treatments and discoveries for a cure by Philip Gold is published by Allen Lane (25). To support the Guardian It is Observer, order your copy at guardianbookshop.com. Delivery fees may apply
The Balanced Brain: The Science of Mental Health by Camilla Nord is published by Allen Lane (25). To support the Guardian It is Observer, order your copy at guardianbookshop.com. Delivery fees may apply
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