Lesson 7: Depression and Other Illnesses
Risky Behavior and the Stress Connection
A study of 5201 men and women aged 65 years and older published in the American Medical Association's Archives of Internal Medicine reported that even milder forms of depression constitute a mortality risk factor in the elderly. An editorial in the same issue felt itself on sufficiently safe ground when it stated: "Suicide explains only a small proportion of the increase in mortality among the depressed ... "
Meanwhile, statisticians are engaging themselves in the exercise of figuring out depression's true kill rate. A 1998 study, The Global Burden of Disease, published by Harvard University Press, credited depression as the fourth leading cause of "disease-burden" in 1990 and will be the single leading cause by 2020.
But depression has many more lethal aspects. Because of the sense of hopelessness and isolation the illness creates, not to mention sluggish cognition, depression plays a key role in influencing reckless and destructive behavior. According to a study published in the Archives of Internal Medicine, depressed patients are more likely to be noncompliant with their treatments (all medical treatments, not just depression), and a study published in the British Medical Journal reports that depressed teens are more likely to engage in risky sex.
Then there is depression's connection to cigarette smoking, alcohol abuse, and drug abuse.
The Stress Connection
A common link between depression and its widespread collateral destruction appears to be stress and trauma. According to the Surgeon General in his landmark Report on Mental Health:
"The compelling impact of past parental neglect, physical and sexual abuse, and other forms of maltreatment on both adult emotional well-being and brain function is now firmly established for depression."
A study published in the British Journal of Psychiatry of rhesus monkeys separated from their mothers found higher levels of the stress hormone cortisol, as well as ACTH (adrenocorticotropic hormone), and lower cerebrospinal fluid levels of noradrenaline. Twenty percent of the infants from the same study also reacted negatively to brief separations from their mothers.
ACTH is a hormone that is part of a biological chain of events beginning when the neuropeptide CRF (corticotropin-releasing factor) is produced by the hypothalamus, which activates the pituitary gland to increase the release of ACTH, which then induces the adrenal gland to release more cortisol. The locus of this activity is known as the hypothalamic-pituitary-adrenocortical (HPA) axis.
Laboratory animals injected with CRF were found to exhibit symptoms of depression, from weight loss to deceased sexual activity. CRF is found in higher concentrations in the cerebrospinal fluid of depressed patients, who also have greater numbers of CRF neurons. CRF is also found in areas of the brain, and appears to be hyper-secreted during depression.
In an Emory University study, four groups of women were subjected to the stressful experience of speaking and performing math tests in front of an audience, then blood samples were taken and heart rates measured. The researchers found that the women with a history of childhood abuse and current major depression exhibited a more than six-fold greater ACTH response to stress than those in the control groups.
According to the authors of the study: "Severe stress early in life is associated with persistent sensitization of the pituitary-adrenal and autonomic stress response, which, in turn, is likely related to an increased risk for adulthood psychopathological conditions."
The findings also indicate that just as stress is likely to be a factor in causing depression, depression can also bring on stress.
The hippocampus and the amygdala are two key regulatory centers located in the cerebral areas of the brain, governing memory storage and emotions, respectively. Both are major nuclei of the limbic system, which underlies emotions. According to the Surgeon General's Report:
"Sensory information enters the lateral amygdala, from which processed information is passed to the central nucleus, the major output nucleus of the amygdala. The central nucleus projects, in turn, to multiple brain systems involved in the physiologic and behavioral responses to fear. Projections to different regions of the hypothalamus activate the sympathetic nervous system and induce the release of stress hormones."
Those hormones, it seems, have plenty of places to go - the heart, the pancreas, the bones, and so on. Scientists have yet to uncover the pathway from a neurotransmitter shutdown in the brain to a tumor or insulin dysregulation elsewhere in the body, but stress is invariably fingered as the likely messenger.
Fortunately, our brain circuits are not permanently welded into place. Our thought patterns can be changed, and cognitive therapy is especially useful in restructuring how we perceive and react to stressful situations. With a bit of practice, "It's the end of the world!" can be altered to, "Let's find a solution." Diet, lifestyle, spiritual practice, and support networks also play a vital role in reducing stress.
One final piece of good news is scientists are developing and testing a "CRF antagonist," believed to be a decade from market. For those 20 to 30 percent of the population who don't respond well to antidepressants, a drug that attacks stress might do the trick.
In the meantime, though, it pays to manage your stress as if your life depended upon the outcome - which, as we are finding more and more every day, it does.
