If you can smell “death”, you may be at greater risk of depression

Jean-Christophe Nebel Read more February 22, 2018

The Smell of Death (1895), Edvard Munch

In 1857, poet Charles Baudelaire wrote the following, at a time when scientists didn’t really know what the smell of death was:

And the sky was watching that superb cadaver Blossom like a flower. So frightful was the stench that you believed You’d faint away upon the grass. The blow-flies were buzzing round that putrid belly, From which came forth black battalions Of maggots, which oozed out like a heavy liquid All along those living tatters.

A couple of decades later, German physician Ludwig Brieger described, for the first time, the main chemical compounds responsible for this “rotting flesh” smell – a mix putrescine and cadaverine – and ever since, researchers have been trying to establish how humans sense this terrifying smell.

Now, a study published in PLOS Computational Biology, may have an answer. Scientists from Kingston University have not only uncovered the smell’s biochemical details the findings, bizarrely, may be able to help treat major mood disorders such as depression.

The smell of death

The “smell of death” is said to consist of more than 400 volatile organic compounds produced by bacteria which break downb tissues in the body into gases and salts.

In recent years, the smell of death has become an important topic of investigation due to its potential for being used as a forensic tool.

Its exact composition and intensity could help in distinguishing human from animal remains, and even help determine the time of death. Such information could be used when training human remains detection dogs, for example.

Our sense of smell relies on the detection of airborne molecules. Proteins belonging to a large family – G protein-coupled receptors (GPCRs) – do this by sensing molecules outside the cell and activating physiological responses. This includes not only smell, but also vision, taste and the regulation of behaviour and mood.

The interaction these proteins have with the outside world makes them major targets for drug development; around one-third of currently available drugs were designed to interact with them. Among the 800 human GPCRs, more than 100 are classified as “orphans” – meaning we don’t know which molecules they are able to sense and how they would interact with them. As a consequence, their potential for developing new drugs is particularly difficult to exploit.

The PLOS research established that two of these orphans – the human TAAR6 and TAAR8 receptors – are able to detect putrescine and cadaverine molecules. In particular, using computational strategies including modelling of the three-dimensional structure of the receptors, the the team revealed exactly how these receptors interact with the “chemicals of death”.

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There are many direct applications of this work. For example, scientists could design drugs to reduce the sensitivity to those odours for people either suffering from increased smell perception (hyperosmia) or working in environments where those compounds are present. They may also be useful for developing a new form of “tear gas” for riot control by creating artificial compounds activating those receptors.

Tackling depression

In the longer term, the findings could also help us tackle major mood disorders. Several specific variations in TAAR6 have previously been associated with conditions which affect a sizeable proportion of the world population: depression, bipolar and schizophrenic disorders. For example, one variant was found to affect how people respond to antidepressants, while another was linked to higher suicide risk.

The research could therefore help develop a new non-invasive method to support diagnosis. Patients with major mood disorders could be offered a “death smell test”, where an abnormal response (experiencing it either more or less strongly than normal) to those odour stimuli could indicate that they carry one of the TAAR6 variants that increases susceptibility to specific mental conditions.

Once diagnosed, sufferers of these conditions could also get specific help from new drugs, and the detected genetic variant could be targeted to alleviate symptoms of the psychiatric disorder. While researchers currently don’t know the exact biochemical mechanisms by which a given variant causes a specific mental health condition, our study is a very useful starting point for uncovering that since it explains the biochemical mechanism involved in the interaction of TAAR6 with external compounds.

It would then be easy to estimate how the presence of a certain variant would affect that interaction. Establishing the link to its physiological response – helping us understand what compounds alter the mental state – would be more challenging. However, even if the detailed pathway between the drug and the final outcome remains unknown, simply testing them in animals and human clinical trials can often be sufficient to demonstrate that they work.

Baudelaire himself was affected by bipolar disorder: the great troubled poet wrote of his thoughts of suicide and even attempted to kill himself when his mistress and muse, Jeanne Duval, was rejected by his family. Could the poet have ever imagined that inside the rotting carcass that he described so vividly may have resided a remedy to his mental condition?

Jean-Christophe Nebel is associate professor in pattern recognition at Kingston University. This article was originally published on The Conversation.

Image: Wikimedia Commons