New technique links lithium distribution in the brain to depression
A new technique is allowing researchers to measure endogenous lithium concentrations in the human brain for the very first time. To test the technique researchers compared lithium levels in post-mortem brain tissue between a suicidal subject and a pair of healthy controls, revealing differences that affirmed the link between lithium levels and mental health.
Alongside being a vital component of batteries, lithium is perhaps best known as a treatment for bipolar disorder. Despite lithium’s proven mood-stabilizing benefits it can quickly become toxic if administered in high doses.
Epidemiological studies have previously found local communities with high natural levels of lithium in their water supply tend to report lower rates of suicide, dementia and violent crime. This had led some scientists to suggest adding trace amounts of lithium to water supplies could improve a community’s mental health.
Exactly how lithium works in the brain is still unknown, and one of the challenges researchers have faced is the inability to effectively measure the distribution of lithium in a human brain. Natural lithium concentrations in a human brain are so small there has been no way to measure distribution – until now.
A new technique called NIK (neutron-induced coincidence) works by flooding a thin slice of brain tissue with neutrons.
"One lithium isotope is especially good at capturing neutrons; it then decays into a helium atom and a tritium atom," says Roman Gernhäuser, from the Technical University of Munich’s Department of Physics.
Detectors can then measure those decay products to provide exact data on lithium concentrations in a given sample. To test this technique the researchers collected post-mortem tissue samples from 150 different locations in a single brain. This allowed the researchers to generate a complete three-dimensional picture of lithium distribution and concentration in a human brain.
"Until now it wasn't possible to detect such small traces of lithium in the brain in a spatially resolved manner," notes Jutta Schöpfer, another researcher working on the project.
The new proof-of-concept study compared brain tissue samples from three deceased subjects. One of the subjects died from suicide, while the other two died from natural causes and served as controls. The primary goal was to investigate the ratio of lithium concentration between white and gray matter.
"We saw that there was significantly more lithium present in the white matter of the healthy person than in the gray matter,” explains Gernhäuser. “By contrast, the suicidal patient had a balanced distribution, without a measurable systematic difference.”
This seems to indicate lithium concentrations in white matter are related to its mood stabilizing effects. These results also validate prior animal studies finding lithium supplementation increases brain concentrations primarily in white matter.
"Our results are fairly groundbreaking, because we were able for the first time to ascertain the distribution of lithium under physiological conditions," says Schöpfer. "Since we were able to ascertain trace quantities of the element in the brain without first administering medication and because the distribution is so clearly different, we assume that lithium indeed has an important function in the body."
It is still unclear how lithium influences metabolism or mood but it is increasingly clear it plays an important role. This new measuring technique can only be used in post-mortem brain tissue samples but the researchers are interested in conducting more investigations in larger cohorts of deceased patients.
The new study was published in the journal Scientific Reports.
Source: Technical University of Munich