Summary: Researchers at the University of Adelaide find that schizophrenia-associated genes in some bipolar patients may explain why those patients do not respond to lithium treatment.
Source: University of Adelaide
Researchers have identified a genetic link that appears to explain why a subset of people with bipolar disorder do not respond to lithium, the long-standing “gold standard” mood stabilizer. An international team led by the University of Adelaide reports that a higher burden of genes previously associated with schizophrenia is linked to poor lithium response in patients diagnosed with bipolar disorder.
Lithium has been used to treat bipolar disorder since the 1950s because of its reliable mood-stabilizing properties. It reduces the frequency and severity of manic and depressive episodes and is known for its capacity to lower suicide risk in affected individuals. Despite these benefits, clinical response to lithium varies widely: roughly 30% of patients show only partial response, more than a quarter exhibit little or no clinical benefit, and many others experience bothersome side effects that limit its use.
Until now, clinicians and researchers have lacked a clear biological explanation for this variability. The new international analysis, appearing in JAMA Psychiatry and led by Professor Bernhard Baune from the University of Adelaide, advances understanding of the genetic factors that influence lithium responsiveness and offers a step toward more personalized treatment for bipolar disorder.
The research was conducted by the international Consortium on Lithium Genetics and examined the genetic profiles of over 2,500 individuals treated with lithium for bipolar disorder. The investigators looked for patterns that distinguished good responders from those who did not experience clinical benefit.
“We found that among patients diagnosed with bipolar disorder, those who showed poor clinical response to lithium shared a common feature: an elevated load of genes linked to schizophrenia,” says Professor Baune, Head of the Discipline of Psychiatry at the University of Adelaide and lead author of the paper. “This does not mean these patients are diagnosed with schizophrenia; rather, a higher burden of schizophrenia-associated genetic variants appears to decrease the likelihood of successful response to lithium.”
In addition to the schizophrenia-related genetic signal, the team identified novel signals implicating the immune system in lithium response. These findings suggest that immune pathways may play a role in the biological mechanisms by which lithium exerts its therapeutic effects, and they point toward new avenues for understanding treatment resistance.
Understanding why some patients with bipolar disorder respond well to lithium while others do not is an urgent clinical need. Reliable predictors of treatment outcome would help clinicians select the most effective and tolerable interventions sooner, reducing trial-and-error prescribing and minimizing exposure to ineffective treatments.
“These findings are an important advance for translational psychiatry,” Professor Baune explains. “When combined with other biomarkers and clinical information, genetic data like ours could contribute to tools that predict treatment response before treatment begins. This work also offers clues about how patients with bipolar disorder and related psychiatric conditions might be stratified for different therapeutic approaches in the future.”
The study underscores the growing potential of genetics to inform psychiatric care without suggesting that a single test will determine treatment for every patient. Instead, the results support a multi-factorial approach in which genetics complements clinical history, symptom patterns, and other biomarkers to guide personalized treatment decisions.
Source: Bernhard Baune – University of Adelaide
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Original Research: The study is published in JAMA Psychiatry.
University of Adelaide. “Gene Breakthrough on Lithium Treatment for Bipolar Disorder.” NeuroscienceNews. Published by NeuroscienceNews, original research in JAMA Psychiatry.