Experts have long recognized that many adults with depression had traumatic experiences as children. For example, loss of a parent to death or divorce is a risk factor for adult depression, as is child abuse. Recent research has gone beyond these observed associations to reveal their biological basis.
"There is now ironclad evidence to support the preeminent role of early trauma in the development of adult psychiatric disorders," Emory University professor Charles B. Nemeroff, M.D., told a group of physicians this week at the annual meeting of the American College of Physicians/American Society for Internal Medicine, in Philadelphia.
Nemeroff specializes in clinical neuroscience — the study of the role of the nervous system in clinical conditions such as depression, anxiety, schizophrenia, and so on. He explained that one of the most important findings so far in this area of research is the discovery that compared to non-depressed folks, patients with depression secrete significantly more of the hormone cortisol.
In non-depressed people, levels of cortisol rise and fall in a circadian rhythm — a pattern that repeats every 24 hours. In depressed patients, cortisol levels are higher, and remain elevated throughout a 24-hour period, without the normal rising and falling. According to Nemeroff, these changes in hormone patterns are caused by higher levels of a brain chemical called corticotropin-releasing factor, which is released by the hypothalamus. corticotropin-releasing factor causes the pituitary gland to release another substance called adrenocorticotrophic hormone, known as ACTH, which in turn leads to the secretion of cortisol.
The hypothalmus and pituitary gland are located at the base of the brain, and control the production of many hormones.
corticotropin-releasing factor is also found in other areas of the brain, particularly those that regulate mood and cognition. Increased levels of this chemical cause some symptoms of depression, such as decreases in appetite, sexual interest, and sleep. When researchers began to look at the spinal fluid of depressed patients, says Nemeroff, they discovered high levels of corticotropin-releasing factor. They also discovered that after successful treatment of depression, these high corticotropin-releasing factor levels returned to normal.
Nemeroff knew that child abuse is associated with an increased risk of depression, substance abuse, anxiety disorders, and suicide. He wanted to see if early experiences caused actual brain changes. He used the cortisol findings to study the long-term effect of early experiences in rats. The basic question, he says, is "whether a deprived or uncertain or frankly abusive relationship could have long-term consequences on neurobiology. Does early experience contribute to the development and vulnerability to various psychopathologies?"
In rats, the answer was a definite yes. Nemeroff and his colleagues removed baby rats from their mothers for three hours every day while they were still nursing, leaving them alone in a separate cage for that period. When the pups were grown, he tested them to see if they behaved differently from their littermates.
Not only did the rats that had been isolated from their mothers as pups have higher levels of corticotropin-releasing factor in their spinal fluid as adults, but they also showed a rat version of depression. For example, when offered sugar water in addition to regular water, the test rats weren’t interested. They also responded differently to stressful situations compared to their littermates, and secreted higher levels of cortisol under stress.
"This was the first demonstration that early trauma (being taken from the mom) causes a life-long, persistent super-sensitive stress response," explained Nemeroff. He noted that once the researchers began removing the pups from their mothers, "the moms never treated the pups that are taken from them the same way they do their litter mates." For example, the mother rats were slower to retrieve these pups when they wandered out of the nest, and spent less time nursing them.
"Now for those of you who are beginning to feel a little bit of guilt about child care, let me assure you that you don’t have to," Nemeroff reassured his audience. He explained that when he took pups from their mothers as before, but instead of isolating them put them with "foster mothers," the pups developed normally and were no different from their former littermates as adults.
But what about humans? Nemeroff also described a clinical study with women that will soon be published in the Journal of the American Medical Association. He looked at four groups of women: those who’d been physically or sexually abused as children and were depressed as adults, those who’d been abused but had no history of psychiatric illness, those who were depressed and were not abused as kids, and those who had no history of either abuse or depression.
The women’s levels of cortisol and ACTH were monitored during tasks that caused moderate stress. Those who’d been abused as children showed significantly higher levels of these chemicals than those who hadn’t, and depressed women who’d been abused had the highest levels of all.
"There is no doubt that there is both a genetic and an experiential component to vulnerability to depression," Nemeroff concluded. His research shows that experience actually changes the way the brain works. On the positive side, he reported, his research also shows that these biological changes can be modified with antidepressants. In both rats and humans, medication restores normal levels of these brain chemicals.