Press Release: Renata Santos, Researcher at the Institut de Psychiatrie et Neurosciences de Paris (IPNP)
Editors' Pick|Jan 26, 2021,12:22pm EST|1 920 views
The Standard Treatment For Bipolar Disorder Doesn’t Work For Everyone, And Now Scientists Might Know Why
Jackie Rocheleau, Contributor
Lithium is often the first treatment option for bipolar disorder. But it’s only effective for about a third of people with the disorder. Scientists may have a clue as to why and discovered a drug target for new treatments.
Bipolar disorder, characterized by episodes of depression and mania, affects about 2.8% of adults in the U.S. and 2.9% of adolescents each year. Medication is one part of the treatment plan and helps balance mood. "Lithium is a classic treatment for bipolar disorder," said Rodrigo Mansur, a psychiatrist and clinician-scientist at the University Health Network in Toronto, and a professor of psychiatry at the University of Toronto. "It has been used for 70 years all over the world."
But lithium has some drawbacks and long-term use may lead to kidney problems. "And sometimes the side effects are really difficult to handle, so it's frequent that patients will stop the treatment," said Renata Santos, a staff researcher at the Institute of Psychiatry and Neuroscience of Paris at the University of Paris.
While decades of studies have produced results showing how effective lithium can be in treating bipolar disorder, a large proportion of individuals don't find relief, and psychiatrists can't reliably predict who will and won't respond well.
"The only reliable way we have is to actually try the medication, and trying medication can be costly, can be time consuming or can be labor intensive," said Mansur. A patient's dose also needs to be carefully managed, and healthcare practitioners need to conduct regular blood tests during treatment to make sure the current dose isn't toxic.
"If we could know beforehand who is going to respond to lithium and who is not, that would save us a lot of work, that would be safer overall and that would probably improve overall outcomes in treating the disease," said Mansur.
An international team of scientists tried to figure out why lithium doesn't work for everyone in this new study. By studying neurons, the researchers saw how lithium might work in the brain. Their results could be used to develop new treatments.
To look at neurons from live people with bipolar disorder without extracting these cells from the brain, the researchers took a blood sample and genetically reprogrammed the patients' lymphocytes, immune cells in the blood, to revert them to an embryonic-like stage. These cells are called induced pluripotent stem cells.
The scientists could then grow and differentiate these cells into the desired cell type. For this study, the scientists wanted the kind of cells heavily affected in bipolar disorder: neurons from a structure in the brain important for learning, memory and emotion, called the hippocampus.
Before this latest research, some of the investigators had previously shown that neurons derived from stem cells of people with bipolar disorder were hyper-excitable, and lithium reduced that excitability. In other words, with lithium treatment, neurons didn't fire or signal to each other as easily as they did before, without lithium treatment. The research group, from the Salk Institute in La Jolla, found that this occurred only in cells of bipolar disorder patients who were responsive to lithium treatment.
When Santos, co-first author of the new study, arrived as a visiting research collaborator at the Salk Institute in California, she wanted to see if she could reproduce those results with cells from a different set of patients.
She not only replicated the earlier findings, but she also saw that the lithium-responsive and the non-responsive neurons looked very different from each other. "So I decided that this cohort would give us the possibility to really look into what gave resistance to lithium in neurons," which led to the present study.
Santos and her collaborators worked with cells from three patients with bipolar disorder who responded to Lithium, three patients who didn’t and four individuals without bipolar disorder, to serve as a control group. All participants were white men, ranging in age from 25 to 62.
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