Editing Major depressive disorder (section)

=== Immune pathogenesis theories on depression ===
The newer field of [[psychoneuroimmunology]], the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression.

[[Depression and immune function|Immune system abnormalities]] have been observed, including increased levels of [[cytokines]] -cells produced by immune cells that affect inflammation- involved in generating [[sickness behavior]], creating a pro-inflammatory profile in MDD.<ref>{{cite journal | vauthors = Krishnadas R, Cavanagh J | title = Depression: an inflammatory illness? | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 83 | issue = 5 | pages = 495–502 | date = May 2012 | pmid = 22423117 | doi = 10.1136/jnnp-2011-301779 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Patel A | title = Review: the role of inflammation in depression | journal = Psychiatria Danubina | volume = 25 | issue = Suppl 2 | pages = S216–S223 | date = September 2013 | pmid = 23995180 }}</ref><ref>{{cite journal | vauthors = Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL | title = A meta-analysis of cytokines in major depression | journal = Biological Psychiatry | volume = 67 | issue = 5 | pages = 446–457 | date = March 2010 | pmid = 20015486 | doi = 10.1016/j.biopsych.2009.09.033 | s2cid = 230209 }}</ref> Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines.<ref>{{cite journal | vauthors = Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD | title = Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls | journal = Brain, Behavior, and Immunity | volume = 87 | pages = 901–909 | date = July 2020 | pmid = 32113908 | doi = 10.1016/j.bbi.2020.02.010 | pmc = 7327519 }}</ref> Research suggests that treatments can reduce pro-inflammatory cell production, like the experimental treatment of ketamine with treatment-resistant depression.<ref>{{cite journal | vauthors = Sukhram SD, Yilmaz G, Gu J | title = Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review | journal = Oxidative Medicine and Cellular Longevity | volume = 2022 | pages = 1061274 | date = 16 September 2022 | pmid = 36160713 | pmc = 9507757 | doi = 10.1155/2022/1061274 | doi-access = free | editor-first = Ajinkya | editor-last = Sase }}</ref> With this, in MDD, people will more likely have a Th-1 dominant immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD.<ref>{{cite journal | vauthors = Rachayon M, Jirakran K, Sodsai P, Sughondhabirom A, Maes M | title = T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression | journal = Scientific Reports | volume = 14 | issue = 1 | pages = 11177 | date = May 2024 | pmid = 38750122 | doi = 10.1038/s41598-024-61865-y | pmc = 11096341 | bibcode = 2024NatSR..1411177R }}</ref>

Another way [[cytokine]]s can affect depression is in the [[kynurenine pathway]], and when this is overactivated, it can cause depression. This can be due to too much [[microglia]]l activation and too little [[Astrocyte|astrocytic]] activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of [[Cytochrome c oxidase subunit 2|COX<sub>2</sub>]]. This, in turn, causes the production of [[Prostaglandin E2|PGE<sub>2</sub>]], which is a [[prostaglandin]], and this catalyzes the production of [[Indolamines|indolamine]], IDO. IDO causes [[tryptophan]] to get converted into [[kynurenine]], and kynurenine becomes [[quinolinic acid]].<ref>{{cite journal | vauthors = McNally L, Bhagwagar Z, Hannestad J | title = Inflammation, glutamate, and glia in depression: a literature review | journal = CNS Spectrums | volume = 13 | issue = 6 | pages = 501–510 | date = June 2008 | pmid = 18567974 | doi = 10.1017/S1092852900016734 }}</ref> Quinolinic acid is an agonist for [[NMDA receptor]]s, so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms.<ref>{{cite journal | vauthors = Hestad K, Alexander J, Rootwelt H, Aaseth JO | title = The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases | journal = Biomolecules | volume = 12 | issue = 7 | pages = 998 | date = July 2022 | pmid = 35883554 | pmc = 9313172 | doi = 10.3390/biom12070998 | doi-access = free }}</ref><!--

[[MRI]] scans of people with depression have revealed a number of differences in brain structure compared to those who are not depressed. Meta-analyses of neuroimaging studies in major depression report that, compared to [[Scientific control|controls]], people who are depressed have increased volume of the [[lateral ventricles]] and [[adrenal gland]] and smaller volumes of the [[basal ganglia]], [[thalamus]], [[hippocampus]], and [[frontal lobe]] (including the [[orbitofrontal cortex]] and [[gyrus rectus]]).<ref>{{cite journal |vauthors=Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC |title=Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder |journal=Archives of General Psychiatry |volume=68 |issue=7 |pages=675–690 |year=2011 |pmid=21727252 |doi=10.1001/archgenpsychiatry.2011.60|doi-access=free }}</ref><ref>{{cite journal |vauthors=Arnone D, McIntosh AM, Ebmeier KP, Munafò MR, Anderson IM |title=Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses |journal=European Neuropsychopharmacology |volume=22 |issue=1 |pages=1–16 |year=2012 |pmid=21723712 |doi=10.1016/j.euroneuro.2011.05.003 |s2cid=42105719 }}</ref> [[Hyperintensities]] have been associated with people with a late age of onset, and have led to the development of the theory of [[Subcortical ischemic depression|vascular depression]].<ref>{{cite journal |vauthors=Herrmann LL, Le Masurier M, Ebmeier KP |title=White matter hyperintensities in late life depression: a systematic review |journal=Journal of Neurology, Neurosurgery, and Psychiatry |volume=79 |issue=6 |pages=619–624 |year=2008 |pmid=17717021 |doi=10.1136/jnnp.2007.124651 |s2cid=23759460 }}</ref> -->