Inflammation in depression

The role of inflammation in depression (and all conditions ostensibly) is a central issue in biomedical research. Every day more research hints at the link between local (neuro/brain) and systemic inflammation.

increased levels of particular markers that indicate neuro (brain/CNS) inflammation have been found and replicated. This indicates that there is a degree of inflammation in the brain during Major Depressive Disorder/Episode(MDD/MDE). Does it precede depressive symptoms or is it simply a consequence of the illness? it appears to be both, inflammation is worsened during depression (immune suppression/dysfunction) and high levels of inflammation can induce depression by deranging multiple neurotransmitter systems creating a positive feedback loop.
Inflammation

1. "This finding provides the most compelling evidence to date of brain inflammation, and more specifically microglial activation, in MDE. This finding is important for improving treatment because it implies that therapeutics that reduce microglial activation should be promising for MDE": 25629589.   In this study a marker for neuroinflammation, Translocator protein density, was used and found to be elevated.
2. "The cascade of antioxidative and inflammatory events is orchestrated by several transcription factors, with Nrf2 and NF-κB having particular relevance to MDD"- PMID: 25580634.  levels of oxidation (requiring high levels of anti-oxidants) is created by activation of genes that regulate inflammation. High levels of oxidation in turn  stimulate the action of these molecules creating a cycle of chronic inflammation.
3. "The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression":PMID 25653939. - This study was consistent with the others in indicating that multiple avenues of inflammation are activated in depression and that unchecked inflammation can lead to depression.
   

Elevated levels of homo-cysteine (Hcy)

1. "the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression" PMID: 25286230 - This is most likely a perpetuating issue, not causal.
   
2. "In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men". PMID 23707477 - Interestingly, woman tended towards the inverse correlation, that is, high levels of Hcy had no correlation with MDD and in fact, trended in the opposite direction of the men in the study. 
3. "Homocysteine also appears to enhance neurotoxicity and damage via glutamate"PMID: 24266734

Agents that reduce inflammation have shown potential in depression:

1. "Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects: PMID 25322082.- Celecoxib is used for pain and inflammation as it is an NSAID.
   
2. "Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action:PMID 25523883"- Curcumin is a potent anti-inflammatory
   
3. "These results suggest that ibuprofen may have an antidepressant effect through inhibition of PGE2 and NO production, especially in depression secondary to chronic inflammation.: PMID 25101545 . 

Taken together, evidence is mounting that inflammation is a significant component of depressive disorders. A sub population of those with chronic recurrent depression may benefit from targeted anti-inflammatory therapy. More specifically, agents that reduce brain inflammation should be trailed.