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Depression (Behavior Endocrinology)
Depression is a state of low mood and aversion to activity, that is capable of affecting a persons thought, behaviors, feeling and more. Depression can be developed due to a multitude of life events; such as the lost of a loved one, any type of abuse (mental, physical, emotional, sexual), being neglected, not feeling good enough, and more. Depression is currently the number one most prevalent mental health disorder and is even predicted to be the second most common health problem come 2020.[4] The reason depression is such a universal epidemic is due to the fact that it's history such as: how it is occurs, why it occurs, when is an individual more susceptible to depression, etc. are relatively unknown due to its infancy.

What is Depression (In Relation to Endocrinology)
Like previously mentioned depression is currently the most common mental health disorder effecting individuals. Stress is a physiological and/ or biological response from a living thing to a stressor. Stress is how the body combats physical, psychological, or even emotional stressors and depression (mood) is something that can either be triggered by stress (biology) or it can result in stress. The hypothalamic pituitary axis in particular is one specific way the body responds to stress (in addition to the autonomic nervous system). Hence why the over activation of the HPA axis is commonly prevalent in depressed individuals, specifically glucocorticoids.

Glucocorticoids and Depression
Role of Glucocorticoids

Glucocorticoids are multifunctional type of steroid due to the fact that they are able to be used as a means of regulating metabolism and immunity, in addition to being an endocrinological response to stress.[5] Specifically, these steroids are capable of regulating neurogenesis, the gaining of new memories, emotional assessment of incidents, and more while stile being able to responding to stress.[5] Glucocorticoids have the ability to suppress inflammatory pathways and prevent the stress outreach from corticotropin releasing hormone, the HPA axis, and the sympathetic nervous system.[6]Glucocorticoids work by binding to glucocorticoid receptors (GR) that are in the hypothalamus or the pituitary. Once, the hormone binds to the GR it results in the negative feedback signaling that inhibits the secretion of more glucocorticoids. Overall glucocorticoids contribute massively to the maintenance of homeostasis in the body. Glucocorticoid effects on Depression

Depression is normally associated with the incapability of the proper function of corticosteroid receptor (in this case glucocorticoids) resulting in the production of neurohormones that could result in depression-like symptoms. Hence, why the number of GR that are able to function are diminished in depressed individuals resulting in the lack of glucocorticoid receptors in people who have been diagnosed with depression to be greater than their counterparts who do not have depression. The over activation of the HPA axis is a sign of glucocorticoid resistance of a lack of effectivity of glucocorticoids on target cells and this lack of recognization of this hormone results in the overproduction of this hormone as a way for the HPA axis to compensate for the ineffective action on target cells. Additionally, individuals with major depression have experienced high levels of cortisol in plasma, urine, and cerebrospinal fluid which ultimately have an affect on the expansion of the pituitary and adrenal gland. Once to see the affects of depression on GRs, an experiment was conducted on rats where they were injected with reserpine (to induce depression-like symptoms in people) and after receiving the drug GRs in the pituitary, hippocampus, and more were decreased. However, the mending of the negative feedback of the HPA axis by glucocorticoids are associated with many antidepressant treatments.

Sex Differences as it Pertains to Depression
Liked mention previously, depression is currently the leading mental health disorder in the world with it affecting mostly women. Women are twice as likely as men to be diagnosed with depression during some period of their lives[7][8][9]. This statistic is made even more evident when going over and investing research experiments in regards to depression. Once individuals reach puberty, from that point on, more females have been diagnosed with depression then males and this trend continues up to and throughout adulthood[8]. It is still not entirely sure why this is the case, however there have been multiple inferences as to why women as twice as likely to develop depression. One being that due to the fact that depression in men and women appears to differ, by women being more likely to show signs of internalized symptoms; meanwhile, men are more likely to have externalizing symptoms[10].

Depression in Women
The reason in which females are more likely to be diagnosed with depression is because it is most likely tied to hormonal changes. Women go through drastic hormonal changes multiple times in their life and even month during the time period of getting their first menstrual cycle to experiencing menopause. Additionally, women experience forms of depression that are associated with changes in ovarian hormones such as estradiol and progesterone. These forms of depression consist of premenstrual dysphoric disorder, postpartum depression, and post-menstrual depression and anxiety[10].


 * Menstruation

When a female gets her period there is a significant amount hormonal changes that her body will go through. When a female is on her menstrual cycle the shedding of the endometrium will occur (which is the bleeding that occurs); in addition to high levels of FSH and low levels of LH, E2 and P[11].


 * Postpartum

Directly after the birth of a child there is a significant decline in the levels of reproductive hormones that is possibly strongly is related to the contribution of the development of depression in women[12]. In fact approximately 15% of women experience postpartum depression. Women are speculated to experience postpartum depression due to the fact that prior to delivery both reproductive hormones and stress hormones rise significantly to help facilitate with delivery; however drop suddenly after the birth of the baby potentially resulting in the stimulation of depressive symptoms. Though there is no concrete evidence it is speculated that the higher levels of CRH during the last few months of pregnancy might be related to postpartum symptoms depicted during a women's first few months after pregnancy.


 * Menopausal

Menopause is the process in which women begin to stop having their menstruation cycles and the ovaries stop the monthly release of an egg. During menopause the ovaries decrease the production of estrogen levels, however the ovaries continue to make testosterone after estrogen stops and continues to do so after menopause. This change is a significant change in hormone level and could be a strong indicator as to why women are 2 to 4 times more likely to experience a major depression episode during menopause[13]. A study concluded that women who are postmenopausal are at a greater risk of depression and they conducted the study by measuring vasomotor symptoms, changes in estradiol, FSH, and testosterone[13].

Depression in Men
Despite women being twice as likely to be diagnosed with depression; men are four times as likely to commit suicide and twice as likely to abuse alcohol and drugs. While there is not a specific pathway for the development of men's depression they do still experience common impairments that people with depression experience such as dysfunctional glucocorticoid feedback, as a result of a hyperactive HPA axis.

Serotonin and Depression
Serotonin is a neurotransmitter that is heavily associated with the contribution of the feeling happiness, however, it is involved in the development of the brains, mood, perception and cognition. There is a controversial statement of serotonin's ability to affect depression; the hypothesis proposes that a decrease in serotonin levels is capable of contributing to the development of depression. However, when it was discovered two of the most effective antidepressants (tricyclic and monoamine oxidase inhibitor) that happened to be relatively effective due to their serotonin-like properties resulted in the use of serotonin selective reuptake inhibitors as a means to help combat depression. Serotonin has no direct affect on depressed individual's mood's; however it had a secondary affect in emotional responses.

Conclusions
Even though copious amount of research has been conducted and leeway has been made there has yet to be a concrete pathway that has been confirmed to be the result of the development of depression. While heavily studied there is so much more to know about depression. For instance, whether or not biological factors such as lack of binding to glucocorticoid receptors cause depression or if environmental and everyday actions affect the way people feel resulting in the resistance of glucocorticoids binding to their receptors. Depression is an epidemic that is infiltrating numerous peoples lives and it is hard to combat due to the fact that, despite being well studied, there are a lot of unknowns when it comes to depression. Knowing that sex hormones play a big role in the development of depression is slight improvement, due to the fact that there is now some kind of rational as to why women are twice as likely to be diagnosed; however the question still lies what is the over lapping factor for women who are depressed and men who are depressed.