Histamines may explain the ineffectiveness of antidepressants for some people, according to new findings.
Many individuals prescribed selective serotonin reuptake inhibitors (SSRIs) do not find them beneficial.
Now, a team from Imperial College London, UK, have investigated the link between inflammation, serotonin and the effectiveness of SSRIs.
Dr Parastoo Hashemi and colleagues measured serotonin movement around the brain by placing microelectrodes into the hippocampus of live mice. They injected the mice with the inflammation-causing toxin lipopolysaccharide.
This led to "robust decreases in extracellular serotonin in the mouse hippocampus," they report in the Journal of Neuroscience.
"We show that these decreased serotonin levels are supported by increased histamine activity (because of inflammation), acting on inhibitory histamine receptors on serotonin terminals."
They add that during this experimentally induced histamine increase, the SSRI escitalopram is less effective because it inhibits histamine reuptake, keeping levels of histamine high.
Furthermore, when histamine is lowered, the drug escitalopram is able to increase circulating serotonin levels, they report.
The authors write: "This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin and points the spotlight at a potentially critical player in the pathology of depression, histamine."
Dr Hashemi commented: “Inflammation could play a huge role in depression, and there is already strong evidence that patients with both depression and severe inflammation are the ones most likely not to respond to antidepressants.
“Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.”
Hersey, M. et al. Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin. Journal of Neuroscience 28 July 2021
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