This article originally appeared in the June 2004 Harvard Mental Health Letter and is provided courtesy of Harvard Health Publications.

Women and depression

How biology and society may make women more vulnerable to mood disorders

All over the world, depression is much more common in women than in men. In the United States, the ratio is two to one, and depression is the main cause of disability in women. One out of eight women will have an episode of major depression at some time in her life. Women also have higher rates of seasonal affective disorder (winter depression), depressive symptoms in bipolar (manic-depressive) disorder, and dysthymia (chronic mild to moderate depression). Why are women so disproportionately affected? And can anything be done about it?

Genetics
Heredity may account for up to 50% of the risk for major depression and could explain some of the gender difference. But depression does not appear more prevalent in the families of depressed men than in the families of depressed women, so a stronger genetic predisposition is apparently not needed to provoke symptoms of depression in men. And the rate of bipolar illness, a strongly genetic disorder, is about the same in both sexes (although some think bipolar II — severe depression and only mild elation — is often overlooked, particularly in women).

Nevertheless, researchers have identified several regions of the genome-containing alleles (gene variants) linked to severe depression in families that are susceptible to the disorder. Some of these links occur only in women, and one of the regions contains a gene related to female hormone regulation.

Real men don’t have moods?
It’s sometimes said that women receive a diagnosis of depression more often than men because they are more likely to acknowledge the symptoms. Men are supposedly more reluctant to admit or even recognize the problem. Instead they may become angry and irritable or drink heavily, and they are less likely to seek professional help. Yet women have a higher rate of depression even in surveys of people who have never sought mental health treatment.

Stress as a trigger
A survey of 30,000 people in 30 countries has found that in similar circumstances, women are more likely than men to say they are under stress. Other studies suggest that women are three times more likely than men to become depressed in response to a stressful event. And women are disproportionately subject to certain kinds of severe stress — especially child sexual abuse, adult sexual assaults, and domestic violence.

Traumatic experiences early in life can have a lasting effect on the brain. A feedback control mechanism normally prevents stress hormones released in an emergency from continuing to circulate when the emergency is over. But if a person is especially vulnerable or the stress is especially severe, the controls may fail. The emergency response is never completely turned off. People suffering from major depression often have high levels of cortisol and other stress hormones. Women may be especially vulnerable because of interactions among stress hormones, female reproductive hormones, and the mood-regulating neurotransmitters serotonin and norepinephrine.

Everyday experiences as well as traumatic ones may provoke stress, leading to depression in women, who are raised to care for others. More often than men, they tend to subordinate their own needs. Many have too much to do in too little time, with too little control over how it is done. In an unhappy marriage, the wife is three times more likely to be depressed than the husband. Another kind of stress is poverty. Women are on average poorer than men — especially single mothers with young children, who have a particularly high rate of depression.

Women also seem to be more physically sensitive to their emotions than men. Fatigue, appetite loss, insomnia, and even pain are symptoms of depression, just as much as sadness, hopelessness, apathy, irritability, and loss of concentration. Researchers analyzing the National Comorbidity Survey found that women were much more likely than men to complain of physical symptoms when depressed. In fact, if they did not count physical symptoms, the rate of depression was the same in both sexes.

Premenstrual disturbance
Premenstrual dysphoric disorder (see Mental Health Letter, June 2001) is a severe form of premenstrual syndrome that occurs in 2%–10% of menstruating women. It is apparently an effect of changing hormone levels, to which some women are unusually sensitive. Some of that sensitivity may be due to interactions between female hormones and neurotransmitters that regulate mood and arousal. Similar symptoms can occur because of the hormonal fluctuations that occur during the years before menopause (the perimenopausal period).

Pregnancy and postpartum
About 10%–15% of mothers become depressed during the first six months after the birth of a child, and the rate of depression during pregnancy may be even higher (see Mental Health Letter, September 2002). The risk factors include poverty, single motherhood, having many children, and an unwanted pregnancy. A temperamentally difficult baby exacerbates the problem, especially if the mother already feels incapable of taking on new responsibilities.

Women who become depressed during this period also have high rates of previous psychiatric disorders, including depression. One study found that two-thirds of women with psychotic postpartum depression, the most severe kind, also developed later psychotic episodes unrelated to pregnancy and childbirth. So it may be that these events are one more source of stress in the lives of women who are vulnerable to depression because of individual psychology or social circumstances.

One symptom common in depressed mothers is excessive worry about their children’s health and safety, along with guilt about being an inadequate mother. These fears are not entirely unrealistic. Depressed mothers are likely to be silent, withdrawn, and unresponsive, yet sometimes overprotective as well. If a baby is irritable and restless from birth, it confirms the mother’s poor opinion of herself and deepens her depression. With older children, there are other problems. They may become angry at her and turn the aggression against other children. Or they may become depressed themselves because they believe the mother’s condition is their own fault.

Drug treatment
Despite some earlier suggestions to the contrary, research indicates that all antidepressant drugs are probably equally effective in both sexes. Although it’s not certain, women may have more side effects, especially diminished libido from selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (Prozac) and sertraline (Zoloft).

SSRIs are the most effective treatment for premenstrual dysphoric disorder. They work relatively quickly and are effective even when taken only during the premenstrual period. Although the evidence is limited, estrogen, either alone or in combination with antidepressants, may help in relieving depression during perimenopause.

Antidepressants are also effective during pregnancy and after childbirth, but benefits and risks must be carefully weighed — especially, of course, the risk to the child of a pregnant or nursing woman. SSRIs do not cause serious birth defects and are considered acceptable for pregnant women. But a study has found some effects on the child’s movements and behavior at birth — possibly a temporary discontinuation syndrome. The mood stabilizer lithium, a treatment for bipolar disorder, can have serious side effects and may raise the risk of birth defects. But bipolar mood swings during pregnancy can be so dangerous that lithium or another drug is necessary.

The risk of exposure to antidepressants in breast milk is probably low, although their long-term effects have not been well studied. Because nursing women may be especially sensitive to the side effects of drugs, starting at a low dose is important. Physicians usually prefer drugs that leave the body quickly and don’t accumulate in breast milk — for example, sertraline as opposed to fluoxetine. It is necessary to avoid drugs that disrupt sleep as well as sedatives that could prevent a mother from hearing her baby’s cries.

Psychotherapy
Psychotherapy is often helpful too, and for pregnant and nursing women psychosocial treatments alone may be preferable. The choices include mutual support groups, interpersonal therapy, cognitive behavioral therapy, marital and family therapies, and psychodynamic therapy. According to most studies, women and men benefit equally from psychotherapy.

Because personal relationships are supposed to be especially important for women, interpersonal therapy is often recommended for them. The therapist and patient review these relationships, emphasizing recent changes such as a death in the family, children leaving home, conflict in a marriage, or the loss of a friend or confidant. Therapist and patient agree to concentrate on one of four issues: grief, role disputes, role transitions, and interpersonal deficits.

Where grief is the issue, the therapist helps the patient complete mourning and find new activities and friends. Role disputes occur in situations like troubled marriages and workplaces. Therapist and patient explore ways to resolve the conflict or, if necessary, end the relationship. Social role transitions — marriage, divorce, pregnancy, childbirth, winning and losing jobs — demand an exploration of the advantages and disadvantages of the old and new roles. Interpersonal deficits, especially loneliness and isolation, may respond to training in social skills and problem-solving.

Alternative and complementary medicine offer another treatment avenue. Depression is probably the most common reason for seeking alternative treatments, especially among women. They may try meditation, massage, acupuncture, and herbal medicines like St. John’s wort. These methods have not been proved effective in scientifically controlled studies, but there is some evidence that they help at least with mild to moderate depressive symptoms.

Recommendations
Despite gains in diagnosis and treatment, unmet needs remain. In 2001, a Summit on Women and Depression, under the sponsorship of the National Institute of Mental Health, brought together several dozen experts to review research and make recommendations on causes, treatment, prevention, and the availability of services. Recommendations in the conference report include:

  more attention to the effects of gender in clinical trials

  more study of genetic and hormonal influences on depression

  more study of the links between depression and specific kinds of stress

  more use of screening tests for depression in women

  better access to services, especially for older women and ethnic minorities

  more use of patient and family education in depression treatment

  development of preventive measures for children of depressed mothers who are at risk for depression.