A new study from the University of Adelaide has uncovered a genetic tool that could help predict how well patients with bipolar disorder (BD) respond to lithium treatment. The research marks a major step toward personalised mental health care and could reduce the trial-and-error process of prescribing medication.
Bipolar disorder affects around 2.2% of Australians and is marked by severe mood swings between emotional highs and lows. Since 1949, lithium has been widely used to stabilise mood in BD patients. But not everyone responds the same: about one-third of patients respond well, another third respond partially, and roughly 25% gain little or no benefit.
Currently, there is no reliable biological marker to predict who will benefit from lithium, leaving doctors to rely on clinical judgment alone.
“About 25% of the variation in lithium response is due to genetic differences,” explained Associate Professor Azmeraw Amare, an NHMRC Emerging Leadership Fellow at the Adelaide Medical School. “By better understanding these genetic factors, we hope to personalise treatment for each patient.”
The study was conducted in collaboration with the International Consortium on Lithium Genetics (ConLi+Gen) and included fellow researchers Associate Professors K. Oliver Schubert and Scott Clark.
The team developed pathway-specific polygenic scores (pPGS), which estimate a person’s genetic likelihood of responding to lithium based on particular biological processes. These processes include brain chemical signalling systems such as dopamine, GABA, and acetylcholine, as well as functions like circadian rhythm and calcium channel activity.
PhD student Nigussie Sharew said that individuals with BD who had higher pPGS scores in the acetylcholine, calcium channel, GABA, and circadian rhythm pathways were more likely to benefit from lithium treatment. On the other hand, those with high scores in the mitochondrial pathway were less likely to respond well.
“This tool gives us biologically meaningful predictions that are directly linked to how lithium works,” said Associate Professor Amare. “It’s a major step toward a genetic test that could guide doctors in prescribing lithium more accurately.”
The research, published in Biological Psychiatry Global Open Science, could help launch clinical trials for lithium response scores and eventually bring these tests into everyday psychiatric care.
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