Harvard Mental Health Letter

Women and depression

It is not clear what underlies the gender gap in this mood disorder.

The phrase "gender gap" is often used in economics and politics to refer to the difference between men and women in earnings or voting behavior. But one of the best documented gender gaps involves a mood disorder — depression.

Women are about twice as likely as men to develop major depression. They also have higher rates of seasonal affective disorder, depressive symptoms in bipolar disorder, and dysthymia (chronic depression).

More than mere sadness, depression can make someone feel as though work, school, relationships, and other aspects of life have been derailed or indefinitely put on hold. It can sap the joy out of once-pleasurable activities and leave someone feeling continuously burdened. This mood disorder may also cause physical symptoms, such as fatigue, pain, and gastrointestinal problems.

It remains unclear why a gender gap exists in depression. Some experts believe that both genders are affected by depression in equal numbers, but women are more likely to be diagnosed with this disorder, in part because men are less likely to talk about feelings and seek help for mood problems. It also may be that depression shows up in different ways in men — for example, as substance abuse or violent behavior.

Others theorize that while both genders are biologically vulnerable to developing depression, women may be more susceptible to harm from life stresses and other environmental factors.

Theories about the gender gap

Genetic vulnerability, hormones, and environmental stress all contribute to the development of depression in both women and men. Researchers have had only limited success in identifying biological factors that might make women more vulnerable to depression.

Genes. Studies in identical twins — who share the same genes — suggest that heredity may account for about 40% of the risk for major depression. Certain genetic mutations associated with the development of severe depression occur only in women.

Hormones. The gender difference in depression first emerges at puberty, with studies finding higher prevalence in girls starting at age 11. Furthermore, the hormonal changes that accompany menstruation each month can bring on mood changes similar to those that occur in depression. And some women are vulnerable to developing depression after giving birth (see "Prenatal and postpartum depression") or during the long transition to menopause — two other stages in a woman's life where hormone levels fluctuate wildly. Researchers have long suspected that the fluctuations in female hormones such as estrogen may underlie women's greater vulnerability to depression.

But while multiple studies have examined this question, they have not been able to prove that these hormonal fluctuations significantly affect mood in large groups of women. The consensus now is that hormonal fluctuations may render individual women more vulnerable to depression at certain times of life — perhaps by interacting with other factors, such as stress.

Stress. Community surveys find that women are more likely than men to say they are under stress. Other studies suggest that women are more likely than men to become depressed in response to a stressful event. Women are also more likely to experience certain kinds of severe stress, such as child sexual abuse, adult sexual assaults, and domestic violence.

Traumatic experiences, especially early in life, can have a lasting effect on the brain. Everyday experiences can also take their toll. Women are more likely than men to be caregivers — taking care of young children, elderly parents, or both. This chronic, low-grade stress may lead to depression. 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.

Other factors. Some research suggests that women may be more likely to ruminate over events than men do, and are more prone to anxiety. These psychological traits may dispose some women to depression. Health and activity levels may also contribute. One intriguing study found, for example, that poor physical health and lack of exercise were associated with the gender gap in depression, even after the researchers controlled for other factors such as employment and stress levels. Physical activity is known to boost mood in people with depression, but this study suggests the advice to get more exercise may be particularly important for women.

Prenatal and postpartum depression

All psychiatric drugs cross the placenta and reach the developing fetus. Thus, during pregnancy, women need to understand how a given drug may affect the developing fetus. But any possible risks of taking a medication need to be weighed against the risks of not taking it. In some cases, untreated depression carries more risk than the drugs used to treat this mood disorder.

The American College of Obstetrics and Gynecology and the American Psychiatric Association recommend that clinicians offer psychotherapy and close monitoring rather than medication for treatment of mild or moderate depression during pregnancy. SSRIs can be used during the first trimester without significantly increasing the risk of fetal heart defects or other major congenital malformations. Use later in pregnancy may cause problems in the newborn.

About 10% to 15% of new mothers experience postpartum depression (within three to six months after delivery). Sleep deprivation, the dramatic changes and stresses that accompany motherhood, and shifts in hormones may all contribute. Treatment can improve the quality of life for both the mother and her child.

Treatment options

For the most part, treatment of depression in women is the same as in men. Clinicians often divide treatment into three phases:

  • In the acute phase, which usually lasts six to 12 weeks, the goal is to relieve symptoms.

  • In the continuation phase, which can last for several more months, the goal is to maximize improvements. At this stage, clinicians may make adjustments to the dose of a medication.

  • In the maintenance phase, the aim is to prevent relapse. Sometimes the dose of a drug is lowered at this stage, or psychotherapy carries more of the weight.

Unique differences in life experience, temperament, and biology make treatment a complex matter; no single treatment is right for everyone. However, research suggests that many people benefit from a combination of medication and therapy.

Antidepressants. More than 10% of women take antidepressants. Although complete remission is difficult to achieve, controlled studies have found that about 65% to 85% of people get some relief from antidepressants, compared with 25% to 40% of people taking a placebo. The research indicates that antidepressants are equally effective in women and men. People respond differently to the same antidepressants, however, so drug choice is made on an individual basis.

Clinicians usually first recommend one of the selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that includes fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft). These drugs act on the serotonin system that affects mood, arousal, anxiety, impulses, and aggression. SSRIs also appear to indirectly influence other neurotransmitter systems, including those involving norepinephrine and dopamine.

Other options include medications that work in different ways. Bupropion (Wellbutrin) works through the neurotransmitters norepinephrine and dopamine, while mirtazapine (Remeron) affects transmission of norepinephrine and serotonin. The drugs venlafaxine (Effexor) and duloxetine (Cymbalta) work in part by simultaneously inhibiting the reuptake of serotonin and norepinephrine. The oldest drugs on the market are not prescribed often, but may be a good option for some women. These include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).

All drugs have side effects. SSRIs frequently hinder sexual response. Women may find that these drugs dampen desire or make it difficult to reach orgasm. A more limited body of research suggests that prolonged use of SSRIs can increase risk of cataracts, gastrointestinal bleeding, bone thinning, and stroke.

TCAs may cause side effects like dry mouth, constipation, or dizziness. MAOIs can cause sedation, insomnia, dizziness, and weight gain. To avoid the risk of a rapid rise in blood pressure, people taking MAOIs must also avoid eating a substance called tyramine, found in yogurt, aged cheese, pickles, beer, and red wine. Some drug side effects subside with time, while others may lessen when a drug dose is lowered. It is sometimes worth trying several different antidepressants in order to find the one that is the best match, balancing the benefits against adverse effects.

Psychotherapy. Most research suggests that women and men benefit equally from psychotherapy. Three broad options exist — cognitive behavioral therapy, interpersonal therapy, and psychodynamic therapy. There is no simple answer as to which one works best. Many patients find that a blended approach — one that draws on elements of different schools of psychotherapy — suits them best.

Cognitive behavioral therapy aims to correct ingrained patterns of negative thoughts and behaviors. The patient learns to recognize distorted, self-critical thoughts, such as "I always screw up," "People don't like me," or "It's all my fault." During cognitive behavioral therapy, a clinician works with the patient to evaluate the truth behind these statements, aiming to transform such automatic thoughts and to recognize events that are beyond anyone's control.

Interpersonal psychotherapy concentrates on the thornier aspects of a patient's current relationships. Weekly sessions over several months help the patient identify and practice ways to cope with recurring conflicts. Typically, therapy centers on one of four specific problems: grief over a recent loss, conflicts about roles and social expectations, the effect of a major life change (such as divorce or a new job), and social isolation.

Psychodynamic therapy focuses on how life events, desires, and past and current relationships affect a patient's feelings and choices. In this type of therapy, the therapist helps a patient identify unconscious defenses against painful thoughts or emotions. For example, someone with an overbearing parent may unconsciously find it difficult to risk developing intimate relationships, out of fear that all close relationships will involve a domineering partner. As patients become aware of these patterns, they may find it easier to overcome such obstacles.

While the duration of psychodynamic therapy can be open-ended, a variation called brief dynamic therapy is limited to a specific amount of time (generally 12 to 20 weeks). It applies a similar lens to a specific emotional problem.

Group, family, or couples therapy may also be part of a plan for treating depression. Group therapy draws on support generated from people in the group and uses the dynamics among them, along with the leader's help, to explore shared problems. Family therapy and couples therapy also delve into human interactions. Like group therapy, the aim is to define destructive patterns — such as scapegoating one family member or enabling a spouse's alcohol abuse — and replace them with healthier ones. These therapies can uncover hidden problems and establish lines of communication. Family therapy is especially useful when one person is struggling with emotions that spill over into the family.

Bromberger JT, et al. "Longitudinal Change in Reproductive Hormones and Depressive Symptoms across the Menopausal Transition: Results from the Study of Women's Health Across the Nation (SWAN)," Archives of General Psychiatry (June 2010): Vol. 67, No. 6, pp. 598–607.

Krishnan V, et al. "Linking Molecules to Mood: New Insight into the Biology of Depression," American Journal of Psychiatry (Nov. 2010): Vol. 167, No. 11, pp. 1305–20.

Leach LS, et al. "Gender Differences in Depression and Anxiety across the Adult Lifespan: The Role of Psychosocial Mediators," Social Psychiatry and Psychiatric Epidemiology (Dec. 2008): Vol. 43, No. 12, pp. 983–98.

Yonkers KA, et al. "The Management of Depression During Pregnancy: A Report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists," General Hospital Psychiatry (Sept.–Oct. 2009): Vol. 31, No. 5, pp. 403–13.

For more references, please see www.health.harvard.edu/mentalextra.