Emotional Regulation and (Peripheral) Inflammation

[dollyvee]

Did a search on the forum for inflammation and realized I've brought it up quite a few times, but may have not linked evidence to inflammation and emotional regulation. Peripheral inflammation is important because it can lead to the activating the central nervous system ie the amygdala, which is responsible for our fight/flight reactions.

The following paper looks at inflammation and the effect on emotional regulation (specifically, ADHD, BPD, etc). There's quite a few things that can fall under peripheral inflammation, including gut dysbiosis, but it also focuses on early life stress as a precursor for peripheral inflammation. IMO while early life stress may have set the initial conditions for peripheral inflammation, it doesn't mean that dysregulated systems in the body can completely be offset with stress reduction. I also think that the terms they are using are clinical (ie BD, BPD, and ADHD) and there is no clinical diagnosis of cptsd. Therefore, to me, the symptoms falling under these clinical diagnosis would/may also be applicable to cptsd. The GI tract is also linked to the vagus nerve, or the centre for fight/flight.

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders
https://pmc.ncbi.nlm.nih.gov/articles/PMC10653990/

The paper states:
"There is also mounting evidence to suggest that dysregulated or imbalanced gut microbiota can increase inflammation in the body and the brain and affect various mental illnesses, including BD [130,139,239]. One of the putative mechanisms connecting the gut, inflammation, and the brain is that gut dysbiosis induces alterations in GI permeability, allowing bacteria and proinflammatory products of their metabolism into the blood. Their presence could trigger or enhance peripheral inflammation, potentially weaken the BBB, and affect brain circuits directly through translocation or indirectly through inflammation, exacerbating a vicious cycle of heightened inflammation and consequent structural and functional damage"

And addressing the connection to BD (bipolar disorder) and IBS:
"Findings favouring an association between inflammation and GI disturbances in BD come from a previous umbrella review, which revealed that irritable bowel syndrome (IBS), which is frequently associated with heightened peripheral inflammation [244], was identified as a potential risk factor for the disorder, meeting class I criteria [193]. This association seems generalizable to mood disorders, as also observed in patients with MDD [245]. Nevertheless, there is preliminary evidence indicating higher IBS rates in BD patients with history of severe ELS, while in patients with MDD the IBS prevalence remains the same regardless of ELS history or severity."

As well:
"Moreover, in one recent work on a cohort of 1072 adult BD patients, the same authors built a data-driven 'allostatic load index' including biomarkers of inflammation (CRP and albumin), cardiovascular risk (diastolic and systolic blood pressure), metabolism of lipids (triglycerides), and metabolism of glucose (fasting glucose), which could predict with 81.1% accuracy if the patients presented non-elevated or elevated emotional reactivity [103]. Notably, the subjects with predicted emotional hyper-reactivity were also the ones with poorer cognitive functioning and overall functioning, independent of other confounding covariates. These promising results suggest that the index was able to capture clinically relevant aspects of the disorder, further emphasizing the link between altered emotional reactivity (which is a starting point for altered ER processes) and integrative measures of body dysfunction, including inflammation."

With regards to ADHD:
"The frequent co-occurrence of ADHD and autoimmune and inflammatory comorbidities, including eczema [323], atopic dermatitis [324], allergic rhinitis, asthma [324], and psoriasis [325] (see also [323] for a meta-analysis) has raised the possibility of a neuropathological role of the immune system and inflammation in ADHD [61,79], as in other EDD."

This article is regarding long Covid, but there are many different latent viral infections that can exist in the body (ie EBV, herpes simplex 1&2, coxsackie etc). Latent viral infections trigger chronic inflammation in the body, which can then lead to CNS activation. Latent viral infections can also be a trigger to autoimmune conditions, which create further inflammation in the body.

The Long COVID Puzzle: Autoimmunity, Inflammation, and Other Possible Causes
https://www.yalemedicine.org/news/the-long-covid-puzzle-autoimmunity-inflammation-and-other-possible-causes

https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15871
Mechanisms of viral persistence in the brain and therapeutic approaches

"Although many viral infections of the CNS are believed to be cleared rapidly and efficiently by the immune system, some viruses become chronic infections and undergo restricted viral replication. During this phase, the immune response is much more tempered; however, it can still cause ongoing brain damage and dysfunction. Some viruses may establish a true latency in the brain. During this phase, no viral progeny is formed and no immune response is generated. It is unclear if there is any persistent brain injury or dysfunction from the latent virus but if the virus reactivates, it may result in manifestations of acute or chronic infections. In addition to the pathologies listed above, neurodegenerative diseases, including dementia, HIV-associated neurocognitive disorder (HAND) [[8]], Alzheimer's disease [[9]], amyotrophic lateral sclerosis (ALS) [[10-12]], and some forms of Parkinson's disease [[13]], are suspected to be associated with chronic viral infections. Unfortunately, viral infections can be difficult to detect in the CNS, thereby making associations with pathologies challenging"

"However, ongoing viral activity in the absence of sterilizing immunity triggers chronic inflammation in the CNS that also contributes to pathology."