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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.

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. Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines. Research suggests that treatments can reduce pro-inflammatory cell production, like the experimental treatment of ketamine with treatment-resistant depression. 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.

Another way cytokines can affect depression is in the kynurenine pathway, and when this is overactivated, it can cause depression. This can be due to too much microglial activation and too little astrocytic activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of COX2. This, in turn, causes the production of PGE2, which is a prostaglandin, and this catalyzes the production of indolamine, IDO. IDO causes tryptophan to get converted into kynurenine and kynurenine becomes quinolinic acid. Quinolinic acid is an agonist for NMDA receptors, 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.

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There is also a connection between the gut microbiome and the central nervous system, otherwise known as the Gut-Brain axis, which is a two-way communication system between the brain and the gut. Experiments have shown that microbiota in the gut can play an important role in depression as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria living in their guts. Bacteria Bacteroidetes and Firmicutes were most affected in people with MDD, and they are also impacted in people with Irritable Bowel Syndrome. Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected. There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression.

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Nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors are effective in treating depression. For instance, Celecoxib, an NSAID, is a selective COX-2 inhibitor– which is an enzyme that helps in the production of pain and inflammation. In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling.

Statins, which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too.

Create new section: Contemporary Shifts on Mental Health Awareness
There are steps being taken in today's society aiming to reduce the stigma around depression and mental health, at least in Western cultures. Companies like BetterHelp aim to increase accessibility to therapy by providing affordable and online therapy options, allowing for people to seek help in an easy and anonymous manner. Using famous sponsors, like Tom Brady, help reduce the stigma about asking for help in regard to mental health too. Likewise, Naomi Osaka has been candid as she talks her own mental health struggles with depression; she discussed her mental health woes when she explained how she doesn't do interviews to"protect her mental health". Also, companies such as hers and hims, make it easy to get medications for anxiety and depression symptoms. These companies allow one to talk to an online physician and receive a personalized prescription without the hassle of going to a doctors office. This accessibility to mental health, and openness about it, care shows a societal shift to encouraging seeking help and providing easy ways to get it, which in turn is helping to destigmatize depression and mental health issues in current society.

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With this, fecal microbiota transplants (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant.