Lithium treatment for bipolar disorder – the key is in the genes

An international research collaboration from the Consortium on Lithium Genetics (ConLi+Gen) and the Psychiatric Genomics consortium (PGC) has for the first time linked genetic predisposition for depression and poor responses to lithium among patients with bipolar disorder.

The research, published today in Molecular Psychiatry was led by Dr Azmeraw Amare from the South Australian Health and Medical Research Institute.

“Since its discovery by an Australian psychiatrist Dr John Cade, lithium has been used as a ‘gold standard’ treatment for bipolar disorder, countering both manic and depressive episodes and decreasing suicide risk,” Dr Amare says.

“Unfortunately, only around one-third of patients have an optimal response to the treatment.

“These study findings fill an important knowledge gap, helping to predict the likelihood of treatment response using patient’s genetic information prior to beginning an intervention.”

The researchers analysed data of more than two-and-a-half thousand patients with bipolar disorder who’d been treated with lithium. They found those patients with a high number of genes associated with major depressive risk were less likely to benefit from mood stabilisers like lithium.

This work builds on previous research by the same team, published in JAMA Psychiatry, that showed bipolar patients with a genetic predisposition to schizophrenia were also less likely to respond to lithium.

Lithium’s mood-stabilising effects were discovered in 1949. Experts aren’t clear on exactly how it works, but believe it helps strengthen nerve cell connections in regions of the brain that regulate mood, thinking and behaviour.

Side effects of the drug can include hand tremors, increased urination and thirst, weight gain and drowsiness.