Take a moment, just a small moment now for all the lives around you that are standing on the edge of an abyss and looking down instead of up. For all the hidden stories and all the hidden hurt you are not seeing – seize this opportunity to learn more, to understand better. You’ve had a busy day – but 117 people in the United States alone have taken their lives today…and 2,925 people have made the attempt .
If you have ever lost a loved one to a mental illness, to suicide whether intentional or unintentional (because I consider suicide in a delusional state as accidental), you will understand the significance, the weight of this topic. If you do not have a mental health problem and are struggling to understand what someone you love is going through, let me offer this quotation from David Foster Wallace:
The so-called ‘psychotically depressed’ person who tries to kill herself doesn’t do so out of quote ‘hopelessness’ or any abstract conviction that life’s assets and debits do not square. And surely not because death seems suddenly appealing. The person in whom Its invisible agony reaches a certain unendurable level will kill herself the same way a trapped person will eventually jump from the window of a burning high-rise. Make no mistake about people who leap from burning windows. Their terror of falling from a great height is still just as great as it would be for you or me standing speculatively at the same window just checking out the view; i.e. the fear of falling remains a constant. The variable here is the other terror, the fire’s flames: when the flames get close enough, falling to death becomes the slightly less terrible of two terrors. It’s not desiring the fall; it’s terror of the flames. And yet nobody down on the sidewalk, looking up and yelling ‘Don’t!’ and ‘Hang on!’, can understand the jump. Not really. You’d have to have personally been trapped and felt flames to really understand a terror way beyond falling.
A mental disorder is not something that is “all in your head”. It’s not something you can “snap out of” or fix by “changing your attitude”. This is a serious medical condition with real biological underpinnings. We cannot be afraid to speak up, because silence kills. We should not be any more ashamed of asking for help with our mental well being than we are to ask for help with infections, cuts, burns, cancer...
The biology is real. New research demonstrates that inflammation and the immune system play a prominent role in mental health disorders [2,3,10,12,14]. A point brought up by one team of researchers was that even the perceived “threat” that triggered the suicidal contemplation could activate inflammatory pathways and further increase the risk .
Did you know that interferon treatment (read that as increasing inflammation) for certain cancers and multiple sclerosis is linked to depression, suicidal ideation and suicide attempts in otherwise psychiatrically healthy patients ? What about other conditions involving inflammatory immune responses such as allergies (5, 6 to read more about seasonal allergens and increased spring time suicides), asthma, multiple sclerosis, systemic lupus erythematosus, and celiac disease? Yep, also linked to suicidal ideation and attempt [3,5]. For the sake of perspective, consider studies that have found these rates in people with the following conditions compared to the rates in the general population
Major Depressive Disorder
Systemic lupus erythematosus
Traumatic brain injury
20x increased suicide risk 
4.9-10% lifetime suicide risk 
2x increased suicide risk 
13.3-26.4% increased suicide risk 
3x increased risk of psychiatric disorder 
3x increased suicide risk 
2x increased suicide risk 
40% develop depression 
3x increased suicide risk 
Let’s take a quick look at how this can happen.
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 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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