Lithium is used to treat mental illnesses such as bipolar disorder, improving the symptoms of mania. We think this may be due to it blocking the actions of certain brain chemicals, notably dopamine.
Amphetamines reproduce some of the features of mania by boosting brain dopamine levels. They can therefore be used as a model of bipolar disorder in otherwise healthy subjects.
Volunteers had a brain scan whilst being given a dose of methamphetamine, creating and investigating a mental state similar to mania. Subjects then took a course of either lithium or dummy 'sugar pills' before returning for a second dose of methamphetamine, again during a scan. We analysed the scans taken before and after each of the drugs given to look at which parts of their brains were affected by amphetamines and whether lithium altered these effects.
We are preparing the findings for publication. Watch this space for news on this!
Does lithium affect brain structure?
Lithium appears to increase the size of the brain even after a short course. Specifically, the amount of grey matter seems to increase. How can this be?
Some argue that lithium helps the brain cells recover from the damage caused by illness. Others think that lithium simply increases the amount of water in the brain. We prefer the third path.
We suspect that lithium does not physically alter the size of the brain, rather it may change the behaviour of water in the tissues. This in turn alters the signal detected during magnetic resonance imaging (MRI) scans to create the illusion of a change in size.
Standard brain scans were performed before and after lithium treatment, together with more advanced image collection techniques.
There were brain MRI differences before and after lithium. This was likely due to a change in the MRI signal being produced rather than an actual increase in brain volume, thus supporting our initial ideas.
When we give a dose of lithium, we don't know how much of it gets into the brain. Strange but true.
We could remove bits of the brain and measure lithium concentration directly, but that would be a bit messy. Instead, we re-tuned our MR scanner so that it could be used to detect lithium. Simple, though not easy.
We can now detect lithium using our MR scanner and a home-made radiowave transceiver. The technique is safe and quick and we are one of only a few centres in the world who can measure lithium in this way. We are constantly working on improvements and developments – for starters, we ordered some posh equipment not made in a shed!
Volunteers were asked to take lithium for about a week before having a brain scan. During the brain scan we tuned into the behaviour of lithium in a magnetic field.
The concentration of lithium in the brain was about 80% of that in the blood. The study did not reveal any significant differences in lithium concentrations in different regions of the brain. So, we know how much lithium arrives in the brain but we can't give you a specific destination... yet!
Effect of Lithium on Proton Longitudinal Relaxation (2019)
Proton longitudinal relaxation (T1) is the time taken for spinning protons to realign with the external magnetic field. This is effectively what happens during an MRI scan! There is some evidence to suggest that corticial T1 is higher in individuals with bipolar disorder, and that lithium reduces this.
Cortical T1 had not yet been measured in separate groups containing lithium treated patients, lithium-naiive patients (new to lithium) and healthy controls.
MRI scans were taken of individuals with bipolar disorder recieving lithium, indiviudals with bipolar disorder naiive to lithium, and individuals without bipolar disorder. T1 was compared in various different areas of the brain.
There were no signiciant differences found between the two groups with bipolar. But, individuals with bipolar had a higher mean T1 than the healthy controls in several brain regions. We think this may mean that there is abnormal tissue structure in the brains of indviduals with bipolar, possibly to do with iron content, water content and other factors. However, the precise mechanism remains unknown...for now!
White matter microstructural properties in bipolar disorder in relationship to the spatial distribution of lithium in the brain (2019)
Lithium treatment is associated with an increase in MRI derived measures of white matter integrity.
The relationship between the spatial distribution of lithium and white matter integrity is unknown.
People with bipolar disorder receiving lithium and people with bioolar disorder on different medications underwent diffusion tensor imaging (DTI - an MRI technology that allows us to measure the microstructural integrity of white fiber tracts).
Lithium-treated individuals with bipolar and healthy control group had a higher Generalised fractional anistrophy (gFA) y than those with bipolar being treated with different medications.This suggests long-term lithium use is associated with greater white matter integrity. We also showed a postive relationship between white mayyer gFA and the spatial distribution of lithium.