Accumulating studies show you to definitely on the male notice testosterone is turned into estrogen of the endogenous aromatase (CYP19). The hormone estrogen you may mediate protective actions thanks to estrogen receptors indicated about men notice (particularly estrogen receptor ?). 23 As well, the presence of androgen receptors in the people pal neurons. 24 Because the testosterone will not cycle in the males as estrogen really does in women, there could be a far more uniform defense inside boys. 23
But not, people also have sexually dimorphic notice nuclei, particularly in the hypothalamus, therefore, the straight down prevalence of depression into the guys is likely much more complex due not just to hormone variations, plus so you’re able to developmental differences in head circuitry
Throughout the extremely practical conditions, this new gender difference in depression prices reflects the fact the people and you will ladies are additional: female has actually 2 duplicates of the X-chromosome, if you’re men possess step one backup each one of X and you can Y chromosomes, the second not-being found in women. Finding out how which practical genetic change confers intimate variations in predisposition to help you mental illness are an elaborate, multilevel puzzle you to remains to be made clear. Society-passionate exposure situations to own depression in women have in all probability a physiological resource, such as for example variations in physical energy and you will characteristics, resulting in a higher frequency regarding depression in females. Perhaps what should changes is societal perceptions to promote equality; but really, it has been taking place regarding Western and it has produced no obvious improvement in the feminine:male depression ratio. 5 Although not, not surprisingly difficulty, recent evidence shows that physiological items, like the type inside the ovarian hormone levels and especially minimizes in the estrogen, could possibly get sign up for the increased frequency away from despair and you may stress from inside the lady which methods to mitigate reduces inside estrogen levels may end up being defensive. Distinguishing ligands that more specifically target your head (age.g., the hormone estrogen receptor-?-choosy ligands) could possibly get protect from anxiety but avoid side effects away from estrogen treatment. 25
Footnotes
The fact that increased prevalence of depression correlates with hormonal changes in women, particularly during puberty, prior to menstruation, following pregnancy and at perimenopause, suggests that female hormonal fluctuations may be a trigger for depression. However, most preclinical studies focus on males to avoid variability in behaviour that may be associated with the menstrual cycle. Nevertheless, primate and rodent studies consistently implicate a role for female hormones, such as estrogen, in depression. Perhaps the most naturalistic depression studies to date to address the role of female hormones involved small groups (n = 4–5) of female macaque primates that formed lifelong social hierarchies with dominant and subordinate females. The latter showed a depression-like phenotype 16 that has been associated with a brain-wide decrease in serotonin 1A (5-HT1A) receptor levels and pal volume. 17 , 18 Interestingly, the reduced hippocampal volume was more extensive in postmenopausal monkeys than in ovarian-intact monkeys, suggesting that ovarian function may be protective. Consistent with this finding, the risk of depression appears to increase during the perimenopausal transition. 19 Emerging evidence indicates that hormone replacement therapy, particularly during the perimenopausal period, can be effective in the prevention of postmenopausal depression in women. 20 Another study involving female macaques examined relocation stress–sensitive alterations in their menstrual cycles and showed depression-related behaviours and reductions in the function of the brain serotonin system. 21 In this light, a recent study has therapist singles dating indicated that women who reported using an oral contraceptive (especially monophasic contraceptives) showed reduced rates of major depression and anxiety compared with nonusers, 22 suggesting that moderating the cycling of estrogen may be protective. Taken together these studies suggest that estrogen may have a protective effect on the pathology that underlies depression and that decreases in estrogen may increase the risk for depression.