Editorial

Why is depression more prevalent in women?

Paul R. Albert, PhD

Major depression is a chronic illness with a high preva- ders global­ly.1 Importantly, before puberty, girls and boys
lence and is a major component of disease burden. Depres- have similar rates of depression; the rate is perhaps even
sive disorders were the second leading cause of years higher for boys.6 At ages older than 65 years, both men
lived with disability in 2010 in Canada, the United States and women show a decline in depression rates, and the
and globally.1,2 When depression-related deaths due to sui- prevalence becomes similar between them.9,11 A greater
cide and stroke are considered, depression has the third prevalence of depression in women is also reflected in pre-
highest global burden of disease. 3 Major depression is scriptions for antidepressant medications. In Canada be-
growing in overall disease burden in Canada and around tween 2007 and 2011, antidepressants were prescribed
the world; it is predicted to be the leading cause of disease more than twice as often to women than men (9.3% v. 4.2%
burden by 2030, and it is already the leading cause in in patients aged 25–44 yr, 2.2-fold; 17.2% v. 8.2% in pa-
women worldwide.4 Between 1990 and 2010 in Canada, tients aged 45–64 yr, 2.1-fold).12 The age discrepancy be-
major depressive disorder showed a 75% increase in tween the peaks in the prevalence of depression (age 14–
­disability-adjusted life years,1 the second greatest increase 25 yr)10 and the prevalence of antidepressant use (> 45 yr)
in prevalence after Alzheimer disease; in comparison, the suggests that young adults with depression may not al-
increase in the United States was 43%.2 At the same time, ways receive antidepressant treatment until many years
the female:male ratio of global disability from major de- after the onset of illness. This delay in medication could
pression remained unchanged at 1.7:1. Although differ- contribute to the higher rates of depression during adoles-
ences in socioeconomic factors, including abuse, education cence and young adulthood and would be important to
and income, may impact the higher rate of depression in study more rigorously comparing treated and nontreated
women,5 this editorial focuses on biological contributors cohorts. Delay in antidepressant treatment might reflect
that are experimentally tractable and may help to under- stigma or under­diagnosis in adolescence. New antistigma
stand how and why depression is more prevalent in and educational programs targeted to youth may help re-
women and lead to better t­ reatments. duce depression in this age group.13
The prevalence of major depression is higher in women Why then is depression more prevalent among women?
than in men;6,7 in 2010 its global annual prevalence was The triggers for depression appear to differ, with women
5.5% and 3.2%, respectively, representing a 1.7-fold greater more often presenting with internalizing symptoms and
incidence in women.1,8 In Canada, the prevalence was 5.0% men presenting with externalizing symptoms.14 For ex­
in women and 2.9% in men in 2002 (1.7-fold greater inci- ample, in a study of dizygotic twins, women displayed
dence in women) and increased to 5.8% and 3.6%, respec- more sensitivity to interpersonal relationships, whereas
tively, in 2012 (1.6-fold greater incidence in women).9,10 men displayed more sensitivity to external career and goal-
The finding of similar female:male prevalence ratios in oriented factors.15 Women also experience specific forms
developed countries and globally suggests that the differ- of depression-related illness, including premenstrual dys-
ential risk may primarily stem from biological sex differ- phoric disorder, postpartum depression and postmeno-
ences and depend less on race, culture, diet, education and pausal depression and anxiety, that are associated with
numerous other potentially confounding social and eco- changes in ovarian hormones and could contribute to the
nomic factors. There is no clear evidence that the rate of increased prevalence in women. However, the underlying
depression is greater in countries where women have mechanisms remain unclear; thus, treatments specific to
markedly lower socioeconomic status than men than in women have not been developed.
countries where there may be more equal footing.5 De­ The fact that increased prevalence of depression correlates
pression is more than twice as prevalent in young women with hormonal changes in women, particularly during pu-
than men (ages 14–25 yr), but this ratio decreases with berty, prior to menstruation, following pregnancy and at
age.9,10 Indeed, starting at puberty, young women are at perimenopause, suggests that female hormonal fluctuations
the greatest risk for major depression and mental disor- may be a trigger for depression. However, most preclinical

Correspondence to: P. Albert, Department of Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Rd, Ottawa
ON K1H 8M5; palbert@uottawa.ca
DOI: 10.1503/jpn.150205

©2015 8872147 Canada Inc.

J Psychiatry Neurosci 2015;40(4) 219

Albert

studies focus on males to avoid variability in behaviour that depression in women. Perhaps what needs to change are
may be associated with the menstrual cycle. Nevertheless, social attitudes to promote equality; yet, this has been oc-
primate and rodent studies consistently implicate a role for curring in the West and has yielded no clear change in the
female hormones, such as estrogen, in depression. Perhaps female:male depression ratio.5 However, despite this com-
the most naturalistic depression studies to date to address plexity, recent evidence suggests that biological factors,
the role of female hormones involved small groups (n = 4–5) such as the variation in ovarian hormone levels and par­
of female macaque primates that formed lifelong social hier- ticularly decreases in estrogen, may contribute to the in-
archies with dominant and subordinate females. The latter creased prevalence of depression and anxiety in women
showed a depression-like phenotype16 that has been associ- and that strategies to mitigate decreases in estrogen levels
ated with a brain-wide decrease in serotonin 1A (5-HT1A) may be protective. Identifying ligands that more specif­
receptor levels and decreased hippocampal volume. 17,18 ically target the brain (e.g., estrogen receptor-β-selective
­Interestingly, the reduced hippocampal volume was more ligands) may protect from depression but avoid adverse
extensive in postmenopausal monkeys than in ovarian-­ effects of estrogen ­therapy.25
intact monkeys, suggesting that ovarian function may be
protective. Consistent with this finding, the risk of depres- Affiliations: From the Department of Neuroscience, Ottawa Hospital
sion appears to increase during the perimenopausal transi- Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
tion.19 Emerging evidence indicates that hormone replace-
Competing interests: None declared.
ment therapy, particularly during the perimenopausal
period, can be effective in the prevention of postmeno-
pausal depression in women. 20 Another study involving References
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