According to experts, a novel explanation for the ineffectiveness of certain experimental medications for schizophrenia may lie in a rare genetic mutation that is inherited from mothers to their children. This mutation entirely blocks a critical brain receptor associated with the disorder.

Researchers at Australia's Flinders University came up with the discovery after studying families impacted by schizophrenia, a serious mental condition that impacts around one out of every hundred individuals globally. Hallucinations, disordered thinking, emotional detachment, and long-term incapacity are common symptoms of the illness. 

The scholarly journal Genomic Psychiatry published the study, which focusses on the brain protein TAAR1. Pharmaceutical firms have been working on pharmaceuticals that target this receptor in an effort to treat schizophrenia in a way that is safer and more effective than current treatments. 

Study senior author Dr Pramod C. Nair described TAAR1's function as more akin to a volume control for dopamine than an on-off switch. Dopamine, a chemical messenger, influences perception, motivation, and mood. 

An Indian family with a mother and two children diagnosed with schizophrenia prompted the researchers to focus on a particular genetic variant called C182F. No mutation was carried by unaffected siblings. 

The researchers used human cells in their lab experiment to see how both wild-type and mutant TAAR1 receptors reacted to endogenous brain chemicals and ulotaront, a medicine that was formerly considered a "breakthrough therapy" by the FDA but ultimately failed major clinical trials. 

The outcomes were astonishing. There was absolutely no reaction from cells that had the defective receptor. 

"What surprised us was the complete silence," stated Mr Britto Shajan, the first author of the study. The receptor was strongly unresponsive. Not even the medicine meant to activate it had any effect. 

This effect was explained by means of sophisticated computer models. The geometry of healthy receptors is maintained open by a tiny chemical bridge. Once the mutation eliminates this bridge, the receptor folds in on itself, blocking the exact location where natural chemicals and medications must attach. 

Individuals with a normal copy of the gene and a defective copy nonetheless have a receptor that operates at around half intensity. This provides additional evidence that the mutation does not harm functional receptors but rather decreases signalling in general. 

Significant ramifications stem from the finding. The mutation is uncommon overall, although it's more common among South Asian groups. The researchers suggest using genetic screening to identify individuals who may not benefit from future therapies based on TAAR1. 

"Genetics can directly influence drug response," Dr Nair noted, referring to the study conducted. "Clinical trials could be spared time, money, and disappointment if this is understood early on." 

These results highlight the rising popularity of personalised medicine in the field of psychiatry, where a patient's genetic makeup may one day dictate their therapy course.