Let’s take a quick look at how this can happen from the perspective of immune and inflammatory pathways.
Your immune system has these wonderful messengers called cytokines and these cytokines can affect neurotransmission in the brain . Analysis of cytokine levels in those who attempt suicide reveals centrally increased cytokine levels in the orbitofrontal cortex (IL-4, IL-13), the anterior prefrontal cortex (IL-1β, TNF-α, and IL-6), and in cerebrospinal fluid (most notably IL-6) [3,4].
We may also be able to use markers of peripheral inflammation to detect suicide risk . For example, it’s been found that S100B levels also correspond with suicidal ideation intensity, and can lead to inflammation-derived glial dysfunction in patients with schizophrenia [3,7]. CRP might be a more familiar marker of inflammation to you. Last month a research team in Arkansas published a study concluding that there is a gradient in CRP levels in those who attempted suicide (highest), had suicidal ideation or were an inpatient psychiatric control .
You may well wonder whether the inflammation was caused by the method of attempted suicide or existed aside from that. Follow up and longitudinal studies have shown the inflammation to be related to depression and suicidal behaviour rather than simply a result of it [3,10,16].
So what happens when we have all this inflammation and how does it affect suicide risk? This can occur through the kynurenine pathway, designed to break down tryptophan. Tryptophan is used to make neurotransmitters like serotonin. However, when there is significant inflammation (such as in the form of cytokines), there is a shift from making serotonin to activating enzymes for tryptophan breakdown instead . This results in increased blood levels of kynurenine, and relates to increased IL-6 in cerebrospinal fluid . This pathway can then produce picolinic acid, quinolinic acid or kynurenic acid. Kynurenic acid has some neuroprotective function (although you don’t want excessive amounts of it) but quinolinic acid causes neuroinflammation [10,11]. Increased quinolinic acid relative to picolinic acid and kynurenic acid is associated with increased suicide risk [10,11].
How do genetic factors fit in? Just last month genetic variation in the SNP rs2121337, responsible for a key enzyme involved in the kynurenine pathway, was found to be associated with neuroinflammation and suicide attempts . This enzyme allows the kynurenine pathway to produce the neuroprotective picolinic acid, and without its proper function the pathway will create more of the neuroinflammatory quinolinic acid .
So it’s not a basic matter of your brain being on fire with CNS-derived inflammation. Pro-inflammatory cytokines from elsewhere in the body can trigger inflammation in the brain, and having this genetic variation can further compound matters, increasing risk for suicide [10,11]. Additionally, neuroinflammation may increase permeability of the blood brain barrier .
What about learned helplessness, hopelessness, impulsivity, aggression, thought patterns and all those other psychological concepts we’ve associated with mental health disorders like depression? Turns out cytokines like IL-6 affect these traits too [3, see 15 for a more in-depth view of the complex IL-6 story].
And inflammation isn’t even the entirety of the different biological processes involved. It’s just a small sample to demonstrate the relevance of biology rather than just psychology.
In the next post we’ll discuss how mental health problems do not have to be a death sentence - there is hope.
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