The Scientist - USA (2020-01 & 2020-02)

01/02.2020 | THE SCIENTIST 35

clues come from epidemiological stud-

ies of Toxoplasma gondii—a parasite

that causes chronic, low-level neuroin-

flammation in humans. A 2018 study of

nearly 300 people in Korea found that

14 percent of people who attempted

suicide tested positive for the parasite,

compared to just 6 percent of healthy

controls—mirroring a correlation found

in several US cohorts.^13 Together, the

findings paint a compelling picture that

neuroinflammation “is part of the story,”

says Melhem.

While depression is not thought of

as an inflammatory disease, signs of

neuro inflammation in the brain have

been repeatedly documented in peo-

ple who suffer from depression, and a

number of anti-inflammatory drugs

show antidepressant effects. Microglia,

the central nervous system’s primary

immune cells and mediators of inflam-

mation, tend to show increased activa-

tion in the brains of people who die by

suicide, Melhem adds, and several stud-

ies have identified elevated concentra-

tions of inflammatory cytokines such

as interleukins IL-2, IL-6, and IL-8 in

people with fatal and nonfatal suicidal

behaviors. One 2019 analysis of nearly

2,000 Mexican-Americans, for exam-

ple, found that blood levels of IL-8 were

elevated in depressed and nondepressed

women who had attempted suicide.^14

How exactly neuroinflammation

might contribute to suicidal behavior is

still unclear, and some recent epidemio-

logical studies have raised doubts about

whether the association exists inde-

pendently from depression. One route

that researchers are exploring is neuro-

inflammation’s interaction with the sero-

tonergic system. In a process thought to

be mediated by microglia, neuroinflam-

mation triggers a shift in the metabo-

lism of serotonin’s molecular precursor,

tryptophan, away from the production

of serotonin and towards other chemi-

cal pathways—potentially reducing sero-

tonin signaling and triggering other sui-

cide-related changes in the brain.

That’s just one hypothesis, says

Melhem, who recently won a grant

NEURAL

TRANSMISSION

Neural communication

via serotonin and other

neurotransmitters such as

glutamate often shows signs

of dysregulation in people

who die by suicide.

INFLAMMATION

People who die by suicide show

signs of increased infl ammation in

the brain while epidemiological data

reveal that some infl ammation-

related health conditions are

associated with higher suicide risk.

SEROTONIN

Disruption of serotonin

signaling has repeatedly been

found in the brains of people

who die by suicide.

SERT

Levels of the serotonin

transporter SERT, which

shuttles serotonin back into

the presynaptic neuron, may

be lower in people who die by

suicide.

5-HT1A AND 5-HT2A

Levels of the serotonin

receptors 5-HT1A and 5-HT2A

may be higher in people who

attempt or die by suicide.

CYTOKINES

Blood levels of infl ammatory

cytokines, particularly some

types of interleukins, have been

found at higher levels in people

who attempt suicide.

MICROGLIA

The brains of people who die

by suicide show higher levels of

microglia activation.

POSSIBLE

CONNECTIONS

Presynaptic neuron

Postsynaptic neuron

Serotonin may

be involved

in directing

immune cells

to sites of

infl ammation.

Infl ammation

may dysregulate

the serotonin

system

via several

pathways.

© LISA CLARK