Why is depression more prevalent in women?

摘要: Major depression is a chronic illness with high prevalence and major component of disease burden. Depressive disorders were the second leading cause years lived disability in 2010 Canada, United States globally.1,2 When depression-related deaths due to suicide stroke are considered, has third highest global burden disease.3 growing overall Canada around world; it predicted be by 2030, already women worldwide.4 Between 1990 depressive disorder showed 75% increase disability-adjusted life years,1 greatest after Alzheimer disease; comparison, was 43%.2 At same time, female:male ratio from remained unchanged at 1.7:1. Although differences socioeconomic factors, including abuse, education income, may impact higher rate women,5 this editorial focuses on biological contributors that experimentally tractable help understand how why more prevalent lead better treatments. The than men;6,7 its annual 5.5% 3.2%, respectively, representing 1.7-fold greater incidence women.1,8 In 5.0% 2.9% men 2002 (1.7-fold women) increased 5.8% 3.6%, 2012 (1.6-fold women).9,10 The finding similar ratios developed countries globally suggests differential risk primarily stem sex depend less race, culture, diet, numerous other potentially confounding social economic factors. There no clear evidence where have markedly lower status there equal footing.5 Depression twice as young (ages 14–25 yr), but decreases age.9,10 Indeed, starting puberty, for mental globally.1 Importantly, before girls boys rates depression; perhaps even boys.6 ages older 65 years, both show decline rates, becomes between them.9,11 A also reflected prescriptions antidepressant medications. 2007 2011, antidepressants prescribed often (9.3% v. 4.2% patients aged 25–44 yr, 2.2-fold; 17.2% 8.2% 45–64 2.1-fold).12 age discrepancy peaks (age yr)10 use (> 45 yr) adults not always receive treatment until many onset illness. This delay medication could contribute during adolescence adulthood would important study rigorously comparing treated nontreated cohorts. Delay might reflect stigma or underdiagnosis adolescence. New antistigma educational programs targeted youth reduce group.13 Why then among women? triggers appear differ, presenting internalizing symptoms externalizing symptoms.14 For example, dizygotic twins, displayed sensitivity interpersonal relationships, whereas external career goal-oriented factors.15 Women experience specific forms illness, premenstrual dysphoric disorder, postpartum postmenopausal anxiety, associated changes ovarian hormones women. However, underlying mechanisms remain unclear; thus, treatments been developed. The fact correlates hormonal women, particularly prior menstruation, following pregnancy perimenopause, female fluctuations trigger depression. most preclinical studies focus males avoid variability behaviour menstrual cycle. Nevertheless, primate rodent consistently implicate role hormones, such estrogen, Perhaps naturalistic date address involved small groups (n = 4–5) macaque primates formed lifelong hierarchies dominant subordinate females. latter depression-like phenotype16 brain-wide decrease serotonin 1A (5-HT1A) receptor levels decreased hippocampal volume.17,18 Interestingly, reduced volume extensive monkeys ovarian-intact monkeys, suggesting function protective. Consistent finding, appears perimenopausal transition.19 Emerging indicates hormone replacement therapy, period, can effective prevention women.20 Another involving macaques examined relocation stress–sensitive alterations their cycles behaviours reductions brain system.21 light, recent indicated who reported using an oral contraceptive (especially monophasic contraceptives) anxiety compared nonusers,22 moderating cycling estrogen Taken together these suggest protective effect pathology underlies depression. Why do men, lack systemic Accumulating research shown male testosterone converted into endogenous aromatase (CYP19). Estrogen mediate actions through receptors expressed throughout β).23 addition, presence androgen confer protection, example neurons.24 Since does cycle consistent protection men. sexually dimorphic nuclei, hypothalamus, so probably complex owing only differences, developmental circuitry.23 In fundamental terms, difference reflects different: 2 copies X chromosome, while 1 copy each Y chromosomes, being present Understanding genetic confers sexual predisposition complex, multilevel puzzle remains clarified. Society-driven factors likely origin, physical strength personality traits, what needs change attitudes promote equality; yet, occurring West yielded ratio.5 despite complexity, variation strategies mitigate Identifying ligands specifically target (e.g., receptor-β-selective ligands) protect adverse effects therapy.25