Gender Differences in Depression and Anxiety Disorders
Gail Erlick Robinson
The objective of this chapter is to highlight sex and gender differences in the prevalence, etiology, presentation, and treatment of depression and anxiety disorders, with special emphasis on the effect of biologic sex and gender roles. The high female:male sex ratio in these conditions is one of the most replicated findings in epidemiology, yet one whose explanation remains uncertain.
Anxiety and depressive disorders are addressed together in this chapter because the distinction between them may be an artificial one. Medical historian Shorter and psychiatrist Tyrer suggest that the distinction originated with the development of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III) by the American Psychiatric Association (1). Before then, anxiety had been considered an integral part of depression but, with the arrival of the new diagnostic classification, the two became separate diagnoses. Despite the results of a nationwide household survey in the United Kingdom that showed mixed anxiety-depression to be the commonest form of affective disorder (2), the presence of a mixed syndrome is now viewed instead as comorbidity. Yet, over 90% of all depressed patients also have anxiety symptoms. In the Epidemiologic Catchment Area (ECA) study, 47% of the respondents meeting lifetime criteria for major depression also met criteria for a co-existing anxiety disorder (3). The National Comorbidity Study (NCS) also found that the presence of an anxiety disorder was associated with an increased risk for major depressive disorder (4).
Although the comingling of depression and anxiety is true for both sexes, comorbid anxiety disorder is more likely in depressed women than in depressed men (5).
Although the comingling of depression and anxiety is true for both sexes, comorbid anxiety disorder is more likely in depressed women than in depressed men (5).
EPIDEMIOLOGY
DEPRESSION
Prior to puberty, there are few differences in the prevalence of depression in males and females (6). (See Manassis, Chapter 4 of this book, on anxiety and depression in childhood.) By contrast, during their reproductive years, women show approximately twice the male frequency of depression. Importantly for the provision of optimum treatment, women are more likely than men to present with atypical depression, anxious depression, and seasonal affective disorder. There are no sex differences in the overall rates of bipolar disorders, but there are some important distinctions, The rapid cycling form of bipolar disorder is more prevalent in women, and women typically experience more episodes of depression relative to manic and hypomanic episodes. Also, the difficult clinical distinction between bipolar II (with hypomania and not mania) and personality disorders such as borderline personality disorder arises more frequently for women than men.
The preponderance of female depression has been found throughout the world, although the exact female:male ratios vary somewhat. As the number of symptoms increases, so does the female:male prevalence ratio. This ratio has, at times, been attributed to a variety of artifacts including women being more willing to talk about feelings; women coming more readily for help; and women’s symptoms being more readily diagnosed as depression. Community surveys, however, have confirmed that the gender difference is found when the bias arising from help seeking is eliminated (3,7). This difference cannot be explained away, as some have speculated, by depressed men self-medicating with alcohol or drugs and, therefore, being diagnosed with substance abuse instead of a mood disorder.
ANXIETY
According to the ECA data, 13% of women compared to 6% of men met 6-month criteria for DSM-III Anxiety Disorders (3). The NCS study found that, not only was the 12-month prevalence of anxiety disorders significantly higher than the 12-month prevalence of substance abuse or affective disorders, but anxiety disorders were also more chronic (4). The majority of anxiety disorders, including specific phobias, agoraphobia with panic, panic disorders, and generalized anxiety disorders, are approximately twice as common in women (4). This difference in prevalence predates adolescence (by age 6, sex differences can already be seen) and increases over time.
DEPRESSIVE DISORDERS
ETIOLOGIC THEORIES OF DEPRESSION
Psychosocial Factors
Beginning at an early age, various psychosocial factors influence the occurrence of depression in women. Women are more likely to be sexually abused as children, and abused children are more likely to become depressed as adults (8). Prolonged separation from parents at an early age greatly increases the risk of depression
in adult women, but this is also true for men. Women have a higher rate of victimization than men, and victimized women have high rates of depression. In the NCS data, however, Kessler (9) controlled for 24 types of life trauma and found that the sex ratio for depression was identical for those with and without previous trauma. Nevertheless, women are more likely to become depressed following stressful life events. (See Chapters 11 and 16 for response to trauma in women.)
in adult women, but this is also true for men. Women have a higher rate of victimization than men, and victimized women have high rates of depression. In the NCS data, however, Kessler (9) controlled for 24 types of life trauma and found that the sex ratio for depression was identical for those with and without previous trauma. Nevertheless, women are more likely to become depressed following stressful life events. (See Chapters 11 and 16 for response to trauma in women.)
As adults, women frequently struggle with role overload, the majority of women working full-time as well as doing 70% of the house and child care. Women are more likely to be depressed if they have young children at home, work outside the home (especially if they would rather stay at home), experience role conflict, or have trouble finding child care (10,11). These factors may contribute to the finding that marriage is not protective for women; married women are more likely to be depressed than married men or single women, the risk increasing further in unhappily married women. The explanation may lie in the fact that women are socialized to look after others, dismissing or minimizing their own needs. They are expected to handle things quietly without resorting to anger; as a consequence, they turn their feelings inward, which results in depression. As well, women are more often financially disadvantaged, and there is a particularly strong relationship between poverty in women and depression. (See Astbury, Chapter 27, in this book.)
Neurochemical and Anatomical Factors
Recent research has focused on the neurochemical and anatomical changes accompanying major depressive disorder (12). Although studies initially centered on the brain monoamine system, researchers more recently have looked at the role of cyclic adenosine monophosphate (cAMP) signal transduction cascade and cAMP-response element (CRE)-binding protein (CREB) (13). Brain-derived neurotrophic factor (BDNF), which protects against stress, appears to be an important gene product regulated by CREB (14). Clinical antidepressant efficacy mirrors the extent of expression of BDNF.
Activation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly seen in depressed patients. There is evidence for elevated cortisol and corticotropin-releasing hormone (CRH) levels, nonsuppression on the dexamethasone suppression test, and a blunted adrenocorticotropic hormone (ACTH) response to CRH. Activation of the HPA axis appears to have prognostic value and is associated with increased risk of depression relapse and even suicide (15). CRH appears to modulate the general stress response as well as depression-related behaviors including appetite and sleep alterations and behavioral despair (16). Early life stress appears to produce longlasting changes in the regulation of CRH neurons and may, therefore, result in a biologic vulnerability to the subsequent development of depression, either directly or by means of increased reaction to stressors later in life. Patients with depression have been found to have volume reductions or other abnormalities in the prefrontal cortex and hippocampus, areas connected to the regulation of mood (17).
Research findings in animal models of depression have corroborated the profound effects of stress on intracellular signal transduction and on the expression of genes that drive fundamental neurotropic and neurotoxic processes, thereby demonstrating the link among environmental stressors, anatomical and neurochemical processes, and depression.
Hormonal Factors
Women’s gonadal steroid hormones are thought to play an important role in the development of mood disorders (18). Mood often appears to fluctuate with the change of hormones. Times of low estrogen, such as the premenstrual and postpartum periods, are times of increased risk for mood disorder. (See Gold, Chapter 18 of this book.) It is possible that monthly cycling may trigger mood changes. We know that the brain is a major target organ for gonadal hormones. A complex interaction exists between gonadal hormones and neurotransmitters such as glutamate, gama-aminobutyric acid, acetylcholine, serotonin, dopamine, noradrenaline, adrenaline, and neuropeptides. Gonadal steroid hormones can affect the synthesis and release of these neurotransmitters, the expression of their receptors, and the membrane permeability of neurons.
Over the course of life, the risk of thyroid disease is four times higher in women than in men. Although thyroid abnormalities seen in depressed patients are probably transitory and stress-induced, subclinical hypothyroidism always needs to be ruled out in depressed women (19).
Genetic Factors
Although genetic factors play a large role in the vulnerability to mood disorders, they do not totally account for the occurrence of depression. Kendler and colleagues (20) found an estimated heritability for the liability to develop a major depressive disorder over a one-year period to be 41% to 46%; they found a lifetime estimated heritability of 70%. This research group postulates that what is inherited is a tendency to overreact to stressful life events. There is no evidence that men and women have a different genetic basis for unipolar depression; however, specific genetic risk factors may vary between men and women. For instance, specific genetic factors may be present in some women that predispose toward premenstrual mood disorder.
For children of bipolar patients, there is a 9% risk of developing the disorder compared to a 1% risk for the general population (21). Early reports of linkage of bipolar disorder to specific sites on the X chromosome have not been replicated. Similarly, reports of illness transmission from mother to child have not held up under scrutiny.
Personality Factors
Specific personality traits have been hypothesized as factors in the high prevalence of depression in women. Women as a group have been described as showing low self-esteem, low perceived control, pessimistic attributional styles, dependency, and overexpressiveness, factors that might result in depression or in being erroneously labeled as depressed. However, studies that carefully controlled for a previous history of depression found no significant association between these personality factors and depression (22). Duggan and colleagues (23), however, found that neuroticism was associated with both a one-year and a lifetime risk of depression and postulated that neuroticism predisposes to depression. More recently, Goodwin and Gotlib found that gender roles, and specifically neuroticism, may indeed play a key role (24). Because neuroticism is a very broad concept, it may be that these studies identified not so much personality factors as alterations in the response to stress, a probable determinant of vulnerability in women predisposed to depression.
Nolen-Hoeksema (25) has hypothesized an interesting relationship between women’s coping styles and subsequent depression. She found that women are
more likely than men to display a self-focused ruminative style of coping with feelings of sadness. Men’s style of distracting themselves rather than ruminating appears, in Nolen-Hoeksema’s studies, to be a more effective way of warding off depression.
more likely than men to display a self-focused ruminative style of coping with feelings of sadness. Men’s style of distracting themselves rather than ruminating appears, in Nolen-Hoeksema’s studies, to be a more effective way of warding off depression.
SUBTYPES OF DEPRESSION
Dysthymic Disorder
Dysthymia affects from 3% to 6% of the population (4). There is no gender difference in children, but the prevalence rate for adult women (8.0%) is almost twice that of adult males (4.8%). The disorder usually begins gradually at an early age. Adolescent girls have been reported to have a greater number of symptoms and more problems with self-esteem than boys, who tend to show more aggressive behavior. Patients frequently suffer from comorbid illnesses such as anxiety or substance abuse. Forty percent have a coexisting major depression (double depression). Although the symptoms of dysthymia are not as severe as those of a major depression, they can nevertheless cause clinically significant distress and impairment in social, occupational, or other functioning.
Major Depressive Disorder (MDD)
MDD is 1.7 to 2.7 times more prevalent in women than in men (5). Girls begin to show an excess of depression over boys beginning around age 13. Ernst and Angst found that females had greater duration, recurrence, chronicity, and global manifestations of MDD than males during early to middle adulthood (26). However, when adjustments were made for recall bias in this retrospective study, these differences disappeared. Analysis of NCS and National Institute of Mental Health (NIMH) data has not found any differences in the course of MDD in men and women whether in recurrence rate, speed of recovery, or chronicity. But chronicity of depression appears to affect women more seriously than men, as manifested by more symptom reporting, poorer social adjustment, and poorer quality of life.
Women suffer more from atypical depression with psychomotor retardation, increased appetite and weight gain, and higher levels of somatic symptoms, ruminations, and feelings of worthlessness and guilt (27). They are also more likely than men to show comorbid generalized anxiety and panic disorders. Depressed women, more than men, also suffer from comorbid thyroid disorders, fibromyalgia, and migraines. No significant gender differences have been found in the risk of such sequelae of depression as early school leaving, having a child at a young age, marrying very early, or being unemployed. Early childbearing, however, when it does occur, leads to more severe consequences in women than in men.
Bipolar Disorder
Bipolar I disorder is equally prevalent in men and women (28). Bipolar II disorders, with episodes of depression and hypomania, occur more frequently in women. Although in 50% of cases in both men and women the onset occurs before age 25, among the other 50%, women generally have a later onset than men, onset in the fifth decade being more common in women.
Women with bipolar illness are more likely than men to have depressive or mixed episodes (29). They also tend toward more dysphoric than euphoric episodes of mania, but male bipolar patients are more likely to complete suicide.
As mentioned earlier, women, more often than men, are rapid cyclers (defined as having as four or more affective episodes per year). Although few have been well studied, a number of hypotheses have been presented to account for this excess of rapid cycling, among them the following: 1) because bipolar women tend to have more depressive episodes, they may more often take antidepressant medication, which increases the risk of developing a manic episode; 2) because women are generally more likely than men to be hypothyroid, subclinical hypothyroidism may initiate rapid cycling; 3) the mood-stabilizing effects of lithium may be offset by its thyrotoxic effect in women, thus making women less responsive; and 4) although there is no prospective evidence linking phases of the menstrual cycle to the onset of rapid cycling, a subset of women may be reactive to the effects of cycling reproductive hormones. No good evidence exists for any of these hypotheses.
As mentioned earlier, women, more often than men, are rapid cyclers (defined as having as four or more affective episodes per year). Although few have been well studied, a number of hypotheses have been presented to account for this excess of rapid cycling, among them the following: 1) because bipolar women tend to have more depressive episodes, they may more often take antidepressant medication, which increases the risk of developing a manic episode; 2) because women are generally more likely than men to be hypothyroid, subclinical hypothyroidism may initiate rapid cycling; 3) the mood-stabilizing effects of lithium may be offset by its thyrotoxic effect in women, thus making women less responsive; and 4) although there is no prospective evidence linking phases of the menstrual cycle to the onset of rapid cycling, a subset of women may be reactive to the effects of cycling reproductive hormones. No good evidence exists for any of these hypotheses.
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