The DAT

(1) Depression is the most commonly treated psychiatric condition and has been documented in history as far back as Hippocrates. An estimated eight million Americans suffer from major depression at any given time. This common disorder causes symptoms which include pervasive unhappiness, disturbed sleeping patterns, inability to experience pleasure, loss of interest in life, decreased sex drive, indecisiveness, and thoughts about dying or suicide. Depression differs from simple grief or mourning responses which are appropriate and normal responses to the loss of a family member or other traumatic experience.

(2) Depression is an unexplainable or unusually prolonged period of sadness. Depression does not affect men and women in equal proportions. In 1990, the World Health Organization found that almost 20 percent of the female population in the developed world will experience an episode of severe depression at some time during their lives. In the United States, 12 percent of women suffer from depression compared to only six percent of men. Studies indicate that depression is two to three times more likely in women than in men.

(3) There are many theories pertaining to why more women suffer from depression than men. Some therapists have suggested that women are more attuned to their emotional state than are men and are thus more likely to recognize depression and seek help. It has also been suggested that physical or sexual abuse, harassment, or sexual discrimination may contribute to depression. An abundance of research has been done to determine the biological causes of depression and explain the disparity in the frequency of the disease in men and women from a biological perspective. It is apparent that depression has a significant biological component that interacts with and reinforces psychological and environmental factors.

(4) Evidence for a genetic predisposition to depression has been mounting for many years. Depression frequently runs in families and relatives of an individual suffering from depression are more likely to experience depression than are members of the general public. Studies of identical twins, who share the same genetic material, indicate that genetic predisposition to the disease is a significant factor. An effort has been made to isolate the genes responsible for causing depression. Various regions on chromosome 18 and 21 have been implicated, as have genes on the X-chromosome and chromosome 11. It appears likely that depression is caused by a number of genes, each contributing a little to the cause of the disease.

(5) While neurochemical research into the causes of depression has long been focused on the production, secretion, binding and reuptake of neurotransmitters in the brain, recent studies have explored other possibilities—namely the role of hormones like cortisol and melatonin in affecting mood and leading to depression.

(6) The hypothalamus is the master organ for hormonal regulation. It releases hormones that regulate hormone secretion by the pituitary. These pituitary hormones in turn function to regulate the secretion of hormones from a number of target organs including the gonads, thyroid gland, and adrenal glands. The hormones secreted by these organs feed back to the hypothalamus and pituitary in a negative manner to limit their own release.

(7) Stress responses are regulated by the interaction of the hypothalamus, pituitary, and adrenal glands. In response to a stressful situation, the hypothalamus increases release of corticotropin-releasing hormone (CRH) which stimulates the pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH travels through the circulation to the adrenal glands causing them to secrete cortisol. Cortisol initiates changes in the body that prepare it to deal with the imposed stress. Appetite is decreased and energy reserves are shunted to the muscles. The heart rate may increase in response to cortisol. When this system functions normally, it allows the human or animal to protect itself from dangerous situations effectively.

(8) In some people, this system is over-active and may lead to depression. For many years, researchers have noted that about half of all severely depressed people have raised levels of cortisol. These raised levels are indicators of fundamental changes in the stress response system in depressed patients. The adrenal and pituitary glands may become enlarged and secrete too much hormone. In particular, increased secretion of CRH has been cited as the cause of increased levels of cortisol. This conclusion has been strengthened by evidence that the number of CRH-secreting cells in the hypothalamus is increased in depressed individuals. Injection of CRH into laboratory animals produces behavioral effects characteristic of depression.

(9) Estrogen is secreted by the ovaries, and may increase the likelihood of depression by priming the body's stress response, exacerbating the problem in women. It appears that estrogen increases cortisol secretion as well as decreases the negative feedback of cortisol on its own secretion. By crippling the feedback system, regulation of cortisol secretion is lost and more cortisol is released. A study by Nicholas Vamvakopoulous at the National Institute of Child Health and Human Development found that increased estrogen concentrations lead to increased CRH secretion by the hypothalamus by promoting the activity of the gene for CRH.

(10) Estrogen and cortisol are not the only hormones that may provide an understanding of female depression. Research by Thomas Wehr of the National Institute of Mental Health (NIMH) indicates that women are more affected by exposure to light and dark than are men. Circadian rhythms, the daily cycle of body function, are regulated by the hormone melatonin. Depression associated with the shortening of daylight in winter is called seasonal affective disorder (SAD) and is directly related to the changes in melatonin secretion.

(11) Melatonin is secreted by the pineal gland, a small structure in the vertebrate brain. The pineal gland descends from the roof of the diencephalon. In some lower vertebrates, the gland has a distinct eye-like structure and studies in the 1980s suggested that the pineal gland was the evolutionary predecessor of the modern eye. Melatonin is secreted in the dark and when the body's internal clock indicates that it is nighttime. As evening comes and the sun goes down, the pineal gland begins to secrete melatonin, perhaps preparing the brain for sleep. When light enters the eye in the morning, melatonin levels drop. Wehr conducted a study to examine the role of melatonin in causing SAD. He exposed test subjects to two controlled environments of light and dark. Subjects were first exposed to 14 hours of darkness a day, followed by only eight hours of darkness per day. The study concluded that periods of melatonin secretion increased in response to longer periods of exposure to darkness.

(12) In the second phase of his study, Wehr sought to determine if this natural sensitivity to changes in day-length persisted when test subjects followed their normal daily schedules. Did the duration of secretions of melatonin change with the seasons? He found that under normal conditions, women were much more sensitive to changes in day length than were men. Women experienced longer periods of melatonin secretion during the winter than during the summer. In contrast, men showed no seasonal changes in melatonin secretion. These results indicate that women are more sensitive to the seasonal changes in day length than are men.

(13) However there is evidence that women with SAD are less sensitive to these seasonal changes in day length. Women with SAD were found to be less likely than woman without SAD to have increased duration of melatonin secretion in winter. This paradox complicates the connection between melatonin secretion and depression in women.

1. Which of the following is not cited in the passage as evidence supporting the connection between cortisol and depression in women?

A. Cortisol has been shown to lead to the expression of genes which contribute to depression.
B. Half of depressed people have increased levels of cortisol.
C.the gland which secretes cortisol is often enlarged in depressed individuals.
D. The number of CRH secreting cells is sometimes increased in depressed people.
E. Estrogen acts to increase the amount of CRH in circulation.

2. Nicholas Vamvakopoulous studied which of the following?

A. The role of cortisol in regulating stress responses in depressed individuals.
B. The relationship between circadian rhythms and depression.
C. The disparity in depression frequency between men and women attributable to social and psychological effects.
D. The role of melatonin in SAD.
E. The effect of estrogen on the activation of the CRH gene.