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Depression may be described as feeling sad, blue, unhappy, miserable, or down in the dumps. Most of us feel this way at one time or another for short periods. But true clinical depression is a mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for an extended time.

= Causes = The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors are at work. == 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. == 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 person's 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 release hormones into the bloodstream that are 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 gland to secrete hormones that 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.] == 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 produceemotional 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. == 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. == 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 - 8% of women during their reproductive years. [See In-Depth 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 had 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 - 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, see In-Depth 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 3 months after delivery. Studies have reported that between 8 - 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, researchers are still trying to determine the best methods for preventing and treating pregnancy-related depression. A review of 15 clinical trials suggested that postpartum depression is best treated by intensive and individualized psychotherapy within a month after a woman gives birth. The researchers found that women are too busy in the weeks before birth to attend prenatal classes that focus on preventing postpartum depression. Doctors are reluctant to give antidepressants to pregnant women. Although most serotonin reuptake inhibitors (SSRIs) do not appear to pose a higher than normal risk for miscarriage or birth defects, paroxetine (Paxil) can cause birth defects. Women who are pregnant or planning on becoming pregnant should not take paroxetine during the first trimester of pregnancy. Most doctors 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.

= Complications of Depression = Depression is often chronic, with episodes of recurrence and improvement. Approximately one-third of patients with a single episode of major depression will have another episode within one year after discontinuing treatment, and more than 50% will have a recurrence at some point in their lives. Depression is more likely to recur if the first episode was severe or prolonged, or if there have been recurrences. To date, even newer antidepressants have failed to achieve permanent remission in most patients with major depression, although the standard medications are very effective in treating and preventing acute episodes. == About 90% of suicides are due to treatable disorders, most commonly depression or substance abuse. People with depression have up to a 15% risk for suicide, with the highest risk in patients who are hospitalized for depression. Some studies indicate that atypical depression poses a higher risk for suicide than typical depression and that dysthymia may pose a higher risk than episodic major depressive disorder. Depressed men are more likely to commit suicide than depressed women, and in the U.S. and around the world, suicide is most common in men older than 60. Suicidal preoccupation or threats of suicide should always be treated seriously in anyone, however. [See: Depression in the Elderly or Depression in Children in this report.] == Major depression in the elderly or in people with serious illness seems to reduce their survival rates, even independently of any accompanying illness. In one study, even minor depression was associated with a higher risk for a shorter life in men (although not in women). Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity. Some research also suggests, however, that depression produces biologic factors, such as low serotonin levels, which trigger stress-related responses in the body that cause blood clotting problems, inflammation, and damage to organs and cells. Effect on Heart Disease and Other Age-Related Problems. Many studies have now reported strong associations between depression and a worse and even shorter old age. Depression increases the incidence and severity of heart attacks, stroke, and death after these events. Depression is also associated with mental decline and even osteoporosis in older people. [For more detailed discussion, see: Depression in the Elderly in this report.] Studies are now showing that depression may contribute to Heart disease.

Click the icon to see a depiction of stroke.

Click the icon to see a depiction of osteoporosis.

Obesity. Both obesity and depression are increasing in American. In a 2002 study, for instance, adolescents who were depressed had a high risk for obesity. The conditions may have common risk factors. For example, being in a lower social and economic group increases the risk for both obesity and depression. Low physical activity may also be a common factor. Few studies have investigated common biologic or behavioral factors. Increasing Sensations of Pain. Depression coincides with increased pain in people with conditions such as those Arthritis or fibromyalgia. Cancer. The relationship between depression and cancer has been explored for years with only a few clear-cut associations (e.g., with pancreatic cancer). Certainly depression and anxiety can have a profound impact on quality of life in cancer patients. A 2002 study reported a worse outlook in cancer patients with a history of depressive symptoms -- but not in patients whose depression occurred after the illness. == Effects of Parental Depression on Children. Depression in parents can have profound effects on their children. It not only increases the risk for depression in their children, but, according to one study, it may even increase a child's risk for many medical conditions (e.g., urinary and genital disorders, headaches, lung problems). Effects on Marriage. In one survey, nearly half of people who suffered from psychiatric disorders before or during their first marriage were divorced, compared to a divorce rate of 36% in those who never suffered from emotional disorders. Spouses of partners with depression are themselves at higher risk for depression. Effect on Work. Depression is well known to adversely affect a person's work life. It significantly increases the risk for unemployment and lower income. Major depression, according to a major 2003 survey, accounts for nearly half of the nation's excess lost productive time (in most cases because of reduced performance at work). Workers with depression also lose significantly more time due to ill health than non-depressed workers. Such lost time is estimated to cost the country billions of dollars each year. == Alcohol and Drug Abuse. About 14% of people with major depression also have an alcohol use disorder and 5% have drug abuse problems. Studies on the connections between alcohol dependence and depression have still not resolved whether one causes the other or if they both share some common biologic cause. Smoking. Depression is a well-known risk factor for smoking, and 26% of people with major depression are nicotine dependent. Nicotine may stimulate receptors in the brain that improve mood in certain people with genetically induced depresssion

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