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Depression and Stress
"Recent stressful events were the most powerful risk factor for an episode of major depression."
Stress - it's there in the environment, from any minor annoyance to an event likely to precipitate a flight-or-fight response to the kind of violation that imprints the mind with severe trauma. It's also there in our biology in the form of hormones that play a key role in mediating our response to the outside world. These same hormones also act as middlemen in a host of co-occurring illnesses.
Each day, we are learning ever more on the relationship between stress and depression, and although there is a lot we still do not know, the presence of stress as a major role-player in the disease process is now considered beyond dispute, with therapies increasingly geared toward neutralizing its vast destructive powers. 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 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 medical cognoscenti refer to the locus of this activity 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 are greater numbers of CRF neurons. CRF is also found in areas of the brain, and appears to be hyper-secreted during depression.
In a just-published 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.
Situational occurrences such as marriage breakup or bereavement also loom large. A study of major depression in twins found that recent stressful events were the most powerful risk factor for an episode of major depression.
According to the study, those with the lowest genetic risk of depression had only a 0.5 percent probability of depression that month, but this shot up to 6.2 percent with exposure to severe stress. Those with the highest genetic risk faced a 1.1 percent probability that skyrocketed to 14.6 percent when stress was present.
The HPA axis is working overtime during these stressful situations, and new studies are beginning to sugggest two areas of the brain responsible for kicking this axis into action:
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."
Two Centers for Disease Control studies recently examined stress on large populations. The studies looked at the effects of armed conflict on groups of Albanians and Serbians, and represent the first of their kind by virtue of being conducted in the midst of war or very soon after, in the region where the conflict occurred. In both studies, survivors were given psychiatric evaluations.
In the first study, two-thirds of the Albanians surveyed reported being deprived of food and water, being in a combat situation, and being close to death. More than half had been forced to flee their homes, and nearly 40 percent had experienced at least eight specific traumatic events, from the murder of a family member to rape.
Not surprisingly, the researchers found a high rate of psychiatric disorder amongst the survivors. What surprised them was how high this figure was - 43 percent, twice their expectations. Adopting less conservative criteria raised the incidence to 83.5 percent.
A study of the Serbian population remaining in Kosovo also surprised researchers, as the findings virtually matched those of the Albanians. Apparently, war in all its terrible horror pays no regard to which group suffers the most. It's simply enough that stress hormones flood into the system like refugees streaming across the border. The stress hormones, of course, are too dumb to know that the war in Kosovo is the cause of their migration into the blood stream. Any war will do, as will any situation approximating war. In this regard, we all represent a population at risk.
Those hormones, it seems, have plenty of places to go - the heart, the pancreas, the bones, and so on. Depression has been linked to illnesses from heart disease to diabetes to stroke to bone loss to cancer. 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."
Our lifestyle choices play an essential role in nipping stress in the bud. A diet of mood-buster foods is simply tempting fate, as is irregular sleep, lack of exercise, and putting off things till the last minute. Ultimately, you may have to lower your expectations - from what you demand of yourself to how clean you want your house to be.
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.
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