Scans Uncover Lithium Patterns In Bipolar Disorder

Scans Uncover Lithium Patterns In Bipolar Disorder

Researchers have utilized a specialized magnetic resonance imaging (MRI) technique to visualize how lithium interacts with the brain in patients with bipolar disorder. The findings, published in The Lancet Psychiatry, suggest that 7Li MRI could enable more personalized treatment by helping medical teams understand the drug's effectiveness and refine prescribing advice.

The study, a collaboration between Newcastle University in the UK and Technische Universität Dresden in Germany, focused on lithium dosing schedules. While lithium is a standard long-term treatment for bipolar disorder, clinicians often vary their prescribing practices, administering the drug either once or twice daily.

Both dosing regimens were found to be equally effective. However, once-daily dosing typically creates higher peaks in blood lithium levels at night and lower levels during the day. Some had argued that the brain smooths out these peaks and troughs, but this research demonstrates that brain and blood levels actually match closely throughout the day.

For medical teams, the discovery that brain levels remain comparable at the standard 12-hour post-dose measurement is considered reassuring. According to the researchers, these patterns may allow prescribers and patients to choose a regimen based on individual needs, such as convenience, treatment adherence, natural circadian rhythms, and specific side effects.

"Lithium is the most effective long-term treatment for bipolar disorder, preventing episodes of illness and reducing the risk of suicide. Not everyone responds to lithium, but for those who do, it is important to individualise treatment to get the best out of this medication."

Dr David Cousins, Director, Newcastle Magnetic Resonance Centre, Clinical Senior Lecturer at Newcastle University and Honorary Consultant Psychiatrist, CNTW NHS Foundation Trust, via miragenews.com

The study involved 41 white European patients who were stable on lithium treatment. Of these, 20 used a once-daily dose and 21 used a twice-daily dose. The participants underwent three consecutive 7Li MRI scans and matched serum sampling over a 10-hour period. This represents the largest 7Li MRI study to date and the first to utilize repeated measures for bipolar disorder.

The imaging technique, developed at Newcastle University and established across Europe via the Horizon 2020 R-LiNK initiative and CEA Neuropsin Paris, allows for the direct visualization of the drug in the brain. Professor Peter Thelwall, Director of the Centre for In Vivo Imaging at Newcastle University, stated that the technique addresses important clinical questions and is driving advances for patient benefit.

The Challenge of Individual Response

Despite its efficacy, lithium responses vary significantly. Some data indicates that only 30–33% of subjects achieve full remission, with another similar percentage reaching partial remission, while the rest show no signs of remission. Furthermore, evaluating a patient's response can take 12 weeks or up to 6 months, a delay that can hinder rapid stabilization.

Current treatment is typically guided by serum lithium concentrations, but the neurobiological mechanism of action remains largely unknown. This gap has limited the development of predictors for how an individual will respond to the drug.

Previous research has shown that brain lithium concentrations, rather than serum levels, may correlate with clinical improvement. Other studies at 3T and 4T MRI have revealed an uneven or heterogeneous distribution of lithium throughout the brain, suggesting the drug may target specific regions. One study localized signals to seven large regions, including the frontal lobe, cerebellum, and brainstem, with consistently high concentrations in the right pallidum and left hippocampus.

Future Research and the BLISS Study

To further this understanding, the Bipolar Lithium Imaging Scan Study (BLISS) is conducting an observational study of 80 adults with bipolar disorder. Using a 7T MR system and a 3D lithium-7 chemical shift imaging (7Li CSI) sequence, researchers aim to link brain measures with clinical response.

The BLISS protocol involves several steps:

• Participants must be 18 or older with a diagnosis of bipolar disorder type I or type II.
• They must have reached stable therapeutic serum lithium concentrations within 4 weeks of the scan.
• Brain lithium concentrations are measured using 7T MRI, with anatomical scans used as an overlay to localize the signal.
• Clinical response is assessed via a validated questionnaire at a 12-month follow-up.

Researchers are using multiple analysis approaches—including region-of-interest analysis targeting the prefrontal cortex, amygdala, anterior cingulate cortex, and hippocampus—to determine which is most relevant for predicting treatment outcomes.