Depressive disorders are among the most frequent illnesses worldwide. The causes are complex and, to date, only partially understood. The trace element lithium appears to play a role. Using neutrons from the research neutron source at the Technical University of Munich (TUM), a research team has now proved that the distribution of lithium in the brains of depressive people is different from the distribution found in healthy humans.
Lithium is familiar to many of us from rechargeable batteries. Most people ingest lithium on a daily basis in drinking water. International studies have shown that a higher natural lithium content in drinking water coincides with a lower suicide rate among the population.
In much higher concentrations, lithium salts have been used for decades to treat mania and depressive disturbances. However, the exact role lithium plays in the brain is still unknown.
Physicists and neuropathologists at the TUM joined forensic medical experts at Ludwig Maximilian University of Munich (LMU) and an expert team from the Research Neutron Source Heinz Maier-Leibnitz (FRM II) to develop a method that can be used to precisely determine the distribution of lithium in the human brain. The team hopes to be able to draw conclusions for therapy as well as to gain a better understanding of the physiological processes involved in depression.
Neutrons detect the slightest traces of lithium
The scientists investigated the brain of a suicidal patient and compared it to the brains of two control people. The investigation focused on the ratio of the lithium concentration in white brain matter to the concentration in the grey matter of the brain.
In order to determine where and how much lithium is present in the brain, the researchers analysed 150 samples from various brain regions – for example, those regions that are presumably responsible for processing feelings. With the FRM II Prompt Gamma-Ray Activation Analysis (PGAA) instrument, the researchers irradiated thin brain sections with neutrons.
Dr Roman Gernhäuser of the Central Technology Laboratory of the TUM Department of Physics explains: ‘One lithium isotope is especially good at capturing neutrons; it then decays into a helium atom and a tritium atom.’ The two decay products are captured by detectors in front of and behind the sample and thus provide information on where exactly the lithium is located in the brain section.
Since the lithium concentration in the brain is usually very low, it is also very difficult to ascertain. Dr Jutta Schöpfer of the LMU Munich Institute for Forensic Medicine says: ‘Until now, it wasn’t possible to detect such small traces of lithium in the brain in a spatially resolved manner.’ Additionally, Gernhäuser points out: ‘One special aspect of the investigation using neutrons is that our samples are not destroyed. That means we can repeatedly examine them several times over a longer period of time.’
A significant difference between depressive patients and healthy persons
Gernhäuser summarises: ‘We saw that there was significantly more lithium present in the white matter of the healthy person than in the grey matter. By contrast, the suicidal patient had a balanced distribution, without a measurable systematic difference.’
Schöpfer is glad to report: ‘Our results are fairly groundbreaking because we were able, for the first time, to ascertain the distribution of lithium under physiological conditions. 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.’
Just a beginning
Gernhäuser admits: ‘Of course, the fact that we were only able to investigate brain sections from three persons marks only a beginning. However, in each case, we were able to investigate many different brain regions which confirmed the systematic behaviour.
‘We would be able to find out much more with more patients, whose life stories would also be better known.’ Gernhäuser further added that it might then also be possible to answer the question as to whether the deviating lithium distribution in depressive persons is a cause or a result of the illness.