Depression and Physical Health

For the vast majority of people with depression, fatigue is a prominent symptom, one of the first to appear and among the last to disappear with treatment. It makes people irritable, unable to concentrate, and generally disinterested in engaging in any activity. It also makes people slow and sluggish, and their energy is not restored by sleep.

The lack of energy is thought to be, at least in part, a response to inflammation. Many of the symptoms of depression are similar to the behaviors seen in many animals in the wild who have been infected by germs—they become less active, they withdraw from other animals, they become less responsive to pleasant-tasting substances. This cluster of responses is known as sickness behavior, and it is not triggered by the infectious agent but by the immune response set off by the threat of infection; it is spearheaded by cytokines, key signaling compounds of the immune system that set the stage for inflammation..

The longer an episode of depression lasts, the greater the likelihood of a recurrence of depression. That is because depression changes the brain in ways that are only now yielding to understanding. The sustained stress that triggers depression releases a cascade of hormones linked to shrinkage of the hippocampus, a part of the brain essential for storing and retrieving memories. Such an effect accounts for the memory problems those with depression typically experience.

It’s not clear whether treatment with current antidepressants always restores the size of the hippocampus. There are other cognitive changes due to untreated depression, such as a sustained bias to recalling negatively coded information, another hallmark of depression.

Untreated depression also changes the activity of substances that help regulate the mitochondria, the energy factories of all cells but which are especially critical to function of the brain because it is such a metabolically active organ. Through this mechanism and others, untreated or chronic depression can pave the way for the cognitive decline of dementia. Increasingly, depression is regarded as a neurodegenerative-like disease.

Statistics indicate that millions of Americans suffer from chronic pain—as well as 20 percent of people worldwide—especially low back pain. Chronic pain is a significant stress on the body that can itself induce depression. Studies show that depression also causes changes in the network of brain areas involved in processing physical pain, including the cortex and lower-brain centers. The pain network appears to be hyperactive in depression, and the degree of activity that can be seen in such areas on brain scans correlates with the severity of depression that patients experience.

Researchers also find that when antidepressants have an effect on depression, it is at least in part by reducing the activity of the pain pathways. What doctors haven’t figured out yet is why heightened pain is experienced so differently among patients, with some experiencing pain as mental anguish and other having somatic complaints of physical pain.

The immune system is now thought to be a significant factor in depression, as scientists recognize the many channels of communication between the immune system and the nervous system. There’s mounting evidence that depression can be caused by inflammation anywhere in the body. One of the many effects of stress, which is so often a precipitant of depression, is to raise levels of cytokines in the body.

Cytokines are one type of immune signaling substances that are released when there is a danger to cells, such as the possibility of infection. They stimulate inflammation as a way to make the cellular environment hostile to invaders. Researchers have long known that levels of inflammatory agents are elevated in patients with depression. They now know that such pro-inflammatory agents can penetrate the so-called blood-brain barrier and change the way the brain functions. They induce many of the behaviors characteristic of depression—reducing energy and activity, minimizing social contact, diminishing pleasurable sensations. There's some evidence that they also weaken the neural connections between parts of the brain essential for processing emotional stimuli.

Depression has profound effects on body metabolism. The elevated levels of the stress hormones associated with depression have, among their many effects, a direct impact on glucose metabolism in the body. The net effect is an increase in insulin resistance, which leads to the accumulation of belly fat. Depression not only raises the risk of diabetes but, independently, of weight gain. In addition, depression especially impairs the motivation to do anything, so those with depression get little exercise, another contributor to weight gain. The gain of belly fat is another way by which depression also makes sufferers prone to heart disease.

Heart disease has long been associated with major depression, both as cause and effect. Feelings of depression are common after a heart attack. Nevertheless, depression is an independent risk factor for cardiac disease. Clinicians and researchers identify several biological pathways by which depression may precipitate a cardiac event. People with depression have elevated levels of inflammatory substances that are known to play a direct role in heart disease.

They also have alterations in blood platelets, cells in the blood that are essential to the clotting mechanism. Another possible link between depression and heart disease is dysregulation of the autonomic nervous system (ANS). The altered stress reactivity common in depression also disrupts the ANS, which controls many aspects of heart function; one effect is an increased likelihood of cardiac arrhythmias.

The stress-related hormones that have detrimental effects on brain function put a burden on cardiac function in other ways—such as by altering glucose metabolism in energy-hungry heart cells. A recent study of nearly 150,000 people in 21 countries reports that cardiovascular events and death increased by 20 percent in people with four or more depressive symptoms compared to people without. The risk increased in all countries but was more than twice as high in urban than rural areas and twice as high in men than in women.