Editing Mood disorder (section)

== Causes ==
Meta-analyses show that high scores on the personality domain [[neuroticism]] are a strong predictor for the development of mood disorders.<ref>{{cite journal |vauthors=Jeronimus BF, Kotov R, Riese H, Ormel J |year=2016 |title=Neuroticism's prospective association with mental disorders: A meta-analysis on 59 longitudinal/prospective studies with 443 313 participants |journal=Psychological Medicine |doi=10.1017/S0033291716001653 |pmid=27523506 |volume=46 |issue=14 |pages=2883–2906 |s2cid=23548727 |url=https://zenodo.org/record/895885}}</ref>

A depressed mood is a predictable response to certain types of life occurrences, such as loss of status, divorce, or death of a child or spouse. These are events that signal a loss of reproductive ability or potential, or that did so in humans' ancestral environment. A depressed mood can be seen as an adaptive response, in the sense that it causes an individual to turn away from the earlier (and reproductively unsuccessful) modes of behavior.{{citation needed|date=April 2022}}

A depressed mood is common during illnesses, such as [[influenza]]. It has been argued that this is an evolved mechanism that assists the individual in recovering by limiting their physical activity.{{sfn|Nesse|Williams|1994|p={{page needed|date=October 2021}}}} The occurrence of low-level depression during the winter months, or [[seasonal affective disorder]], may have been adaptive in the past, by limiting physical activity at times when food was scarce.{{sfn|Nesse|Williams|1994|p={{page needed|date=October 2021}}}} It is argued that humans have retained the instinct to experience low mood during the winter months, even if the availability of food is no longer determined by the weather.{{sfn|Nesse|Williams|1994|p={{page needed|date=October 2021}}}}

Much of what is known about the genetic influence of clinical depression is based upon research that has been done with identical twins. Identical twins have exactly the same genetic code. It has been found that when one identical twin becomes depressed the other will also develop clinical depression approximately 76% of the time. When identical twins are raised apart from each other, they will both become depressed about 67% of the time. Because both twins become depressed at such a high rate, the implication is that there is a strong genetic influence. If it happened that when one twin becomes clinically depressed the other always develops depression, then clinical depression would likely be entirely genetic.<ref>{{cite web |url=http://www.erissolver.com/sq/What-are-the-main-causes-of-depression-or-depressive-disorders-(psychology) |title=What are the main causes of depression or depressive disorders (psychology)? |publisher=Eris Consulting |access-date=10 June 2015 |url-status=dead |archive-url=https://web.archive.org/web/20150610110247/http://www.erissolver.com/sq/What-are-the-main-causes-of-depression-or-depressive-disorders-(psychology) |archive-date=10 June 2015}}</ref>

[[Bipolar disorder]] is also considered a mood disorder and it is hypothesized that it might be caused by [[mitochondrial dysfunction]].<ref name="Pieczenik, Steve R 2006">{{cite journal |author1=Pieczenik, Steve R. |author2=Neustadt, John |title=Mitochondrial dysfunction and molecular pathways of disease |journal=Experimental and Molecular Pathology |volume=83 |issue=1 |pages=84–92 |year=2007 |pmid=17239370 |doi=10.1016/j.yexmp.2006.09.008}}</ref><ref>{{cite web |title=Mitochondrial dysfunction and bipolar disorder |date=29 September 2017 |url=https://bipolarnutrition.wordpress.com/2017/09/29/mitochondrial-dysfunction-and-bipolar-disorder/ |access-date=1 October 2017 |url-status=live |archive-url= https://web.archive.org/web/20171001165713/https://bipolarnutrition.wordpress.com/2017/09/29/mitochondrial-dysfunction-and-bipolar-disorder/ |archive-date=1 October 2017}}</ref><ref>{{cite journal |vauthors=Scainiab, Giselli, Rezinc, Gislaine, Carvalhod, Andre, Streckb, Emilio L, Berkef, Michael, Quevedo, João |title=Mitochondrial dysfunction in bipolar disorder: Evidence, pathophysiology and translational implications |journal=Neurosci Biobehav Rev |volume=68 |pages=694–713 |year=2016 |doi=10.1016/j.neubiorev.2016.06.040 |pmid=27377693|s2cid=207092957 }}</ref>

===Sex differences===
Mood disorders, specifically stress-related mood disorders such as anxiety and depression, have been shown to have differing rates of diagnosis based on sex. In the United States, women are two times more likely than men to be diagnosed with a stress-related mood disorder.<ref name="Sex-dependent effects of chronic va">{{cite journal |last1=Rosinger |first1=Zachary |title=Sex-dependent effects of chronic variable stress on discrete corticotropin-releasing factor receptor 1 cell populations |journal=Physiology & Behavior |date=2020|volume=219 |page=112847 |doi=10.1016/j.physbeh.2020.112847 |pmid=32081812 |pmc=7540729 }}</ref><ref>{{cite journal |last1=Blume |first1=Shannon |title=Disruptive effects of repeated stress on basolateral amygdala neurons and fear behavior across the estrous cycle in rats |journal=Scientific Reports |date=23 August 2019 |volume=9 |issue=1 |page=12292 |doi=10.1038/s41598-019-48683-3|pmid=31444385 |pmc=6707149 |bibcode=2019NatSR...912292B |doi-access=free }}</ref> Underlying these sex differences, studies have shown a dysregulation of stress-responsive neuroendocrine function causing an increase in the likelihood of developing these affective disorders.<ref>{{cite journal |last1=Weiser |first1=Michael |title=Androgen regulation of corticotropin-releasing hormone receptor 2 (CRHR2) mRNA expression and receptor binding in the rat brain |journal=Experimental Neurology |date=26 July 2008 |volume=214 |issue=1 |pages=62–68 |doi=10.1016/j.expneurol.2008.07.013 |pmid=18706413|pmc=2891365 }}</ref> Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis could provide potential insight into how these sex differences arise. Neuropeptide corticotropin-releasing factor (CRF) is released from the paraventricular nucleus (PVN) of the hypothalamus, stimulating adrenocorticotropic hormone (ACTH) release into the blood stream. From here ACTH triggers the release of glucocorticoids such as cortisol from the adrenal cortex. Cortisol, known as the main stress hormone, creates a negative feedback loop back to the hypothalamus to deactivate the stress response.<ref>{{cite journal |last1=Ramot |first1=Assaf |title=Hypothalamic CRFR1 is essential for HPA axis regulation following chronic stress |journal=Nature Neuroscience |date=March 2017 |volume=20 |issue=3 |pages=385–388 |doi=10.1038/nn.4491 |pmid=28135239|s2cid=5017743 }}</ref> When a constant stressor is present, the HPA axis remains overactivated and cortisol is constantly produced. This chronic stress is associated with sustained CRF release, resulting in the increased production of anxiety- and depressive-like behaviors and serving as a potential mechanism for differences in prevalence between men and women.<ref name="Sex-dependent effects of chronic va"/>