Studies by Hugo Critchley's group showed that administering typhoid vaccine to healthy individuals induces acute dysphoria, increased feelings of social isolation, and changes in depressive brain circuitry.
"the folks in London, Hugo Critchley's group, they tended to use typhoid, and they showed it, right? You know, you give normal folks a shot of typhoid, which activates a sort of acute, mild—it's not, you know, feels like a sledgehammer, right? I mean, this is more like a ping. But you do that, and yeah, people report feeling more socially isolated, they feel more dysphoric, and you see changes in their brain that sort of speak to depressive brain functioning." (said at 0:20:21)
Hugo Critchley's group (Harrison et al., 2009) demonstrated in double-blind, randomized crossover trials that administering typhoid vaccination to healthy volunteers induces mild systemic inflammation (elevated IL-6), acute mood reduction/dysphoria, and altered activity and connectivity in brain regions implicated in depression (specifically the subgenual anterior cingulate cortex and mesolimbic circuits). However, the specific demonstration of acute inflammation increasing feelings of social disconnection and loneliness was established using endotoxin challenge models (e.g., Eisenberger et al., 2010), rather than Critchley's typhoid fMRI studies.
- supports: Inflammation causes mood changes through alterations in subgenual cingulate activity and m… (Biological psychiatry 2009)
"Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6." (abstract, results, passage verified)
pubmedfull study (doi) - context: Inflammation and social experience: an inflammatory challenge induces feelings of social d… (Brain, behavior, and immunity 2010)
"Results revealed that endotoxin led to significant increases (from baseline) in IL-6 and TNF-alpha levels as well as feelings of social disconnection and depressed mood. Moreover, controlling for increases in social disconnection eliminated the relationship between exposure to inflammatory challenge and depressed mood." (abstract, results, passage verified)
pubmedfull study (doi)