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An in-depth report on the causes, diagnosis, treatment, and prevention of depression.

Alternative Names

Seasonal Affective Disorder; Selective Serotonin-Reuptake Inhibitors


The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors are at work.

Genetic Factors

Because depression runs in families, and has a strong genetic component, there is compelling evidence that it is a biologic phenomenon. Data from family, twin, adoption, and genetic studies have confirmed this. Studies have found that first-degree relatives of patients with depression are two to six times more likely to develop the problem than individuals without a family history.

Biologic Factors

Evidence now strongly supports the theory that depression has a biologic basis and that certain brain chemicals and neural pathways responsible for regulating mood and associated behaviors are altered.

Neurotransmitter Abnormalities. The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain).

  • Serotonin. Perhaps the most important neurotransmitter in depression is serotonin. Among other functions, it is important for feelings of well-being. One 2003 study indicated that serotonin improves a persons ability to pick up emotional cues from other people, which is important for healthy relationships. Another study further suggested that people deficient in serotonin were less likely to take risks for high rewards than those with normal levels.
  • Other Neurotransmitters. Other neurotransmitters possibly involved in depression include acetylcholine and catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine, and epinephrine (also called adrenaline). Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety. Increased CRF concentrations appear to interact with serotonin and have been detected in patients with either depression or anxiety.
Endocrine glands
Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary to secrete hormones which determine the pace of chemical activity in the body (the more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity).

The degree to which these chemical messengers are disturbed is determined by other factors, such as light, structural abnormalities in the brain, sleep disorders, or genetic susceptibility. For example, researchers have identified a defect in the gene known as SERT, which regulates serotonin and has been linked to depression.

Reproductive Hormones. In women, the female hormones estrogen and progesterone most likely play a role in depression. [See Box Depression in Women.]

Insomnia and Sleep Disorders

Studies estimate that 20% of people with insomnia suffer from major depression and 90% of people with depression have insomnia. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may actually be a symptom of later emotional disorders in some cases.

Depression as Adaptive Strategy

Some experts theorize that low mood is an adaptive response to situations in which expectations fail to match achievements (such as with an unrequited love affair, career failure, or a challenge of authority). In its healthy state, the pain this response causes provides both an incentive to disengage and a passive, withdrawn state that allows a period of thought before changing direction. Depression as a disorder (characterized by pervasive pessimism, low self-esteem and total lack of initiative) may develop if there are constant unachievable objects or goals and there are no positive relationships to help a person change direction. (Such cases could certainly occur in highly competitive societies that lack strong social support and where the media holds up unattainable images as desirable.) Such a theory does not, however, rule out biologic or other factors that can contribute to depressive disorders.

Depression in Women

Women, regardless of nationality or socioeconomic level, have significantly higher rates of depression than do men. The causes of such higher rates appear to be a mix of biologic and cultural factors.

Hormonal Fluctuations and Life Stages

Extreme hormonal shifts can trigger emotional swings in all women. The role of hormones in depression is not clear, however, and is mostly based on observations of depression during specific stages in female development. Female hormones undoubtedly play some role in premenstrual dysphoria, postpartum depression, and SAD. These forms of depression recede or stop after menopause.

Early Puberty. Girls who go through puberty early (reaching the midpoint at 11 years or younger) are more likely to experience depression during adolescence than girls who mature later.

Premenopause. Premenopausal women between the ages of 20 and 45 were most susceptible to depression, with 22% of this age group reporting symptoms of major depression. Specifically, premenstrual dysphoric disorder (severe depression before a period) affects an estimated 3% to 8% of women during their reproductive years. [See Well-Connected Report # 79 Premenstrual Syndrome.]

Perimenopause. Depression often occurs around menopause (the perimenopausal period), when, in addition to hormonal changes, other factors such as cultural pressures favoring young women, sudden recognition of aging, and sleeplessness are involved. In one study, more than half of perimenopausal women were diagnosed with major depression. Women who suffered depression before menopause may also have a risk for entering the premenopausal period at a slightly earlier age than women without depression.

Postmenopause. Once women pass into the postmenopausal period, studies suggest that average depression scores are nearly as low as those in premenopausal women. In fact, many women report that after menopause, previous bouts of depression, particularly when caused by seasonal changes or premenopausal syndrome, recede or stop completely.

Premenstrual Dysphoric Disorder

The syndrome of severe depression, irritability, and tension before menstruation is known as premenstrual dysphoric disorder (PDD or PMDD), also called late-luteal dysphoric disorder. It affects an estimated 3% to 8% of women in their reproductive years. A diagnosis of PDD depends on having five or more standard symptoms of major depression that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward. PMDD has features of both anxiety and depression disorders, although experts increasingly believe it is a distinct disorder with specific biochemical abnormalities. [For more information,seeWell-Connected Report #79 Premenstrual Disorder.]

Depression and Pregnancy

Depression During Pregnancy. Pregnancy is certainly an occasion of great celebration for most women most of the time. However, emotions during that time are not always straightforward, and depression is a common (although most often a temporary) companion. A 2001 study found that depression during pregnancy was more common than depression after pregnancy, with the highest depression scores occurring in week 32.

Prenatal depression can affect a mother's sleep, physical activity, adherence to care, and appetite--all of which can affect the unborn child.Some research suggests that depression during pregnancy may pose a risk for later language and behavior problems in the child later on.

Miscarriage. Miscarriage poses a very high risk for depression, particularly in the first month after the loss. Older women with no previous successful pregnancies and those with a history of depression are at particular risk during this time. (There has been some concern that depression increases the risk for miscarriage in the first place, but a 2003 study found no evidence to support this, at least in the first 22 weeks.)

Postpartum Depression. Most new mothers experience weeping, irritability, and confusion for a few days following childbirth. Such symptoms, known as the "baby blues," are not considered to be indicators of postpartum depression, however, unless they persist in severe form nearly every day for more than a week or two.

Postpartum depression can first develop as long as three months after delivery. Studies have reported that between 8% and 20% of women have diagnosable postpartum depression within that time. In one study, 5% of these women had suicidal thoughts. (It should be noted that many male partners of new mothers also suffer from depression around the birth of a child.)

Studies have not found any association between a higher risk for postpartum depression and a woman's educational level, the gender of the child, whether or not she breastfeeds, whether or not the pregnancy was planned, or whether the delivery was vaginal or cesarean. The rapid decline of reproductive hormones that accompany childbirth is likely to play the major role in postpartum depression in susceptible women. Fluctuating thyroid hormones can also contribute to depression. Different studies have suggested that women who are more sensitive to hormone fluctuations and so at greater risk for postpartum depression have one or more of the following conditions:

  • A history of prior depressive episodes.
  • A family history of mood disorders.
  • Stressful life events (such as being a new mother and having an infant with medical problems).
  • Lack of social support or feeling as if it is lacking.

Treatment During and After Pregnancy. Although a mother's depression during and after pregnancy can have serious effects on her child, treatment is problematic.

Psychotherapy is helpful in the short term of women with postpartum depression but may not be any more helpful than routine care from a physician in the long run.

Physicians are reluctant to give antidepressants to pregnant women. Encouraging studies to date, however, suggest that selective serotonin reuptake inhibitors (SSRIs) do not pose a higher than normal risk for miscarriage or birth defects or later problems in the offspring. High doses, however, may reduce birth weight. Also, taken late in pregnancy, however, SSRIs may affect serotonin levels in the newborn. Studies on the effects on infants of nursing women taking SSRIs report very low levels of the medications in blood but no observable negative effects on the babies. More research is needed, however, and most physicians advise women to avoid, if possible, any medications during pregnancy and nursing.

The Theory of Affiliate Behaviors and Oxytocin

Depression in women is more likely to follow interpersonal problems, while in men depression tends to be attributed to stressful life events. One theory about the higher risk of depression in women concerns affiliate behaviors, which are those that involve activities surrounding relationships, and a peptide called oxytocin (OT).

Oxytocin is found in mammals and stimulates uterine contraction during labor and milk release during nursing. And evidence suggests it may also play a role in affiliate behaviors such as maternal caregiving and sexual bonding after puberty. Under primitive conditions, the release of OT after puberty coincided with early mating and breeding. In modern cultures, however, there is typically a long delay between puberty and childbirth. Some experts theorize that release of OT and the subsequent inability to mate and procreate creates feelings of loss and separation in women that can lead to depression.

This theory is backed up by some studies suggesting that young women most vulnerable to depression are those who are also most sensitive to separation from parents, friends, or loved ones.

Social and Economic Factors in Women

The role that work, marriage, and children play in a woman's depression is complex. Many women feel that they must be everything to everyone and at the same time feel as if they are no one at all. Such a self-image is common and should be strongly considered as a major contributor to depression in many women, particularly those who work and have small children. The following are results of studies suggesting the difficulty of assessing the relationship between a woman's social status and depression, however.

In a report on women worldwide issued by the World Health Organization in 1996, married women with children had a higher risk for depression than did married childless women, single women, or single or married men.

A survey of women in the Boston area reported, however, that women between the ages of 36 and 44 who had children were significantly less likely to be depressed than childless women. And the more children they had, the less depressed they tended to be. This study targeted older premenopausal women. The difference between this study and others may be due to the presence of older children, who might add a supportive emotional network, rather than dependent toddlers.

The perceived low status and isolation accompanying the role of housewife may play a role in a young mother's depression. A European study reported that depression increased in men and fell in women between 1980 and 1995, a period coinciding with more women entering the work force. (Work outside the home that fails to provide social support, however, will not necessarily help protect against depression.)

Other studies in the U.S. have reported that grandmothers who care for their grandchildren and mothers of toddlers, regardless of whether they worked outside the home or not, have a very high risk for depression.


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