A new clue to how lithium may affect the brain has been found in new research into quantum biology at the University of Surrey. The study investigates how a quantum property of lithium atoms could influence chemical reactions involving vitamin C in the brain.
While lithium has been used as a first-line treatment for the long-term management of bipolar disorder for more than 70 years, scientists still do not fully understand how it produces its therapeutic effects in the brain.
In a new study published in PLOS One, Surrey researchers used computational chemistry and quantum simulations to investigate whether part of the answer could lie in ‘nuclear spin’ – a quantum property that makes an atom’s nucleus behave like a tiny magnet, allowing it to influence nearby electrons and potentially change the outcome of chemical reactions.
The study focused on the two stable isotopes of lithium – lithium-6 and lithium-7. Although chemically almost identical, their atomic nuclei have different quantum spins, and previous in vivo studies have found that this means they can produce different biological effects, including differences in their ability to reduce hyperactivity in rats.
The team modelled whether this difference could influence a chemical reaction involving flavin, a vitamin B2-derived molecule that helps proteins transfer electrons, and a radical derived from vitamin C (a form of the molecule with an unpaired electron). Vitamin C is abundant in brain cells called neurons and helps protect the brain against oxidative stress, while its radical can retain its spin state for relatively long periods, giving quantum effects more time to potentially influence the reaction.
Simulations showed that lithium-6 and lithium-7 could affect the reaction differently because of their different nuclear spins. The size of the predicted isotope effect was similar to that derived from previous animal studies comparing the behavioural effects of lithium-6 and lithium-7.
Amina Mouhamed, PhD researcher at the University of Surrey and first author of the study, said:
“What fascinated us was the possibility that two almost chemically identical forms of lithium could influence biology differently because of a quantum property of their nuclei.
“If this difference could affect chemical reactions and ultimately contribute to changes in behaviour, it would demonstrate a remarkable link across scales, from atomic nuclei to biological processes. That possibility remains to be tested experimentally. Confirming such a link could open a new avenue for treatment design: fine-tuning how a medicine works by changing its isotopic composition”
While the study does not show that quantum effects are responsible for lithium’s therapeutic action, it identifies a possible mechanism that researchers can now test experimentally.
Dr Marco Sacchi, Associate Professor of Computational Chemistry at the University of Surrey and senior author of the study, said:
“Lithium is an extraordinary drug. It has transformed the treatment of bipolar disorder, yet after decades of clinical use we still do not completely understand what it does at the molecular level.
“Our results do not show that quantum spin effects are responsible for lithium’s therapeutic action. What they do show is that such a mechanism is physically plausible in a biologically relevant molecular system and can generate an isotope effect of the right order of magnitude. That gives us a hypothesis we can now begin to test experimentally.”
The researchers hope that future experiments comparing lithium-6 and lithium-7 in systems involving vitamin C could test whether the isotope-dependent effects predicted by the model occur in real chemical or biological systems.
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