Trans-3-Methyl-2-hexenoic acid

TMHA & Schizophrenia

It has long been claimed that schizophrenia patients exhibit a particular peculiar body odor, and it has been postulated the odor may be caused by underlying metabolic abnormalities associated with the condition, among other factors. Initial studies identified the causal component as TMHA, however, subsequent studies failed to reproduce such results, with subsequent researchers suggesting the initial research may have had misidentified impurities in samples as TMHA due to poor methodology. However, a 2007 study found schizophrenia patients to have reduced olfactory sensitivity to TMHA, possibly indicating sensory habituation; the decreased ability to smell the substance due to the presence of the substance as a constant component of subjects' own sweat and body odor. Furthermore, the researchers noted a positive association between reduced ability to smell TMHA and greater severity of disorganised and negative symptoms.

An allusion to TMHA and its purported link to the smell of the mentally ill is made in the 1996 David Foster Wallace novel, Infinite Jest, the 1988 Thomas Harris novel The Silence of the Lambs, and the 2025 comic book Absolute Martian Manhunter #2 by Deniz Camp and Javier Rodríguez.

References

References

1. (2006). "Individual Comparisons of the Levels of (''E'')-3-Methyl-2-Hexenoic Acid, an Axillary Odor–Related Compound, in Japanese". Chemical Senses.
2. (2005). "Human sweaty smell does not affect women's menstrual cycle".
3. (December 1970). "Failure to detect trans-3-methyl-2-hexenoic acid in the sweat of schizophrenic patients". Clinica Chimica Acta.
4. (January 2007). "Olfactory sensitivity through the course of psychosis: Relationships to olfactory identification, symptomatology and the schizophrenia odour". Psychiatry Research.
5. (1969-10-17). "Sweat in schizophrenic patients: identification of the odorous substance". Science.
6. (July 1973). "Studies of trans-3-methyl-2-hexenoic acid in normal and schizophrenic humans". Journal of Lipid Research.
7. Foster., Wallace David. (1996). "Infinite jest: a novel". Little, Brown and Co.
8. (April 23, 2025). "Absolute Martian Manhunter". DC Comics.