Cardiff: New link identified for bipolar disorder

Research lead

A possible mechanism has been identified for how lithium treats bipolar disorder.

While lithium has been established for more than 50 years as one of the most effective treatments for manic depression, clinically termed bipolar disorder, scientists have never been entirely sure exactly why it is beneficial.

Now, new research by scientists at Cardiff University has suggested a possible mechanism of action, opening the door for better understanding of the illness and potentially more effective treatments.

Risk of bipolar disorder is heavily influenced by genetic predisposition, but is a complex genetic trait and, to date, genetic studies have provided little insight into its molecular origins. The researchers have taken the alternative approach of investigating the genetics of lithium sensitivity.

Laboratory studies have shown that the enzyme prolyl oligopeptidase (PO) controls a set of genes that determine sensitivity to lithium. Among these genes is ImpA2, which like PO activity itself, has been associated with differences in sensitivity to lithium from one patient to another. These results highlight a mechanistic link that could explain these differences.

Adrian Harwood of Cardiff School of Biosciences, who led the research, which was funded by the Wellcome Trust, said, “We still cannot say definitively how lithium can help stabilise bipolar disorder. However, our research has uncovered a new cell signalling process with links to bipolar disorder.

“This introduces a new mechanism and more candidate genes, whose study could lead to greater understanding of the causes of bipolar disorder, better diagnostic tests and new types of drugs that are more effective and have fewer side effects than lithium.”