How do we measure dopamine in the living human brain and what do these measures tell us about the nature of dopamine dysfunction in schizophrenia?
In the brain of humans, most of the dopamine cells are located in the anterior part of the midbrain or the midbrain itself, especially in the striatum.
There are various methods to measure dopamine in the living human brain,
Microdialysis, a method with relatively small damage to the tested tissue and high sensitivity. A microdialysis probe is surgically inserted into the brain region that we want to study. The front end of the probe is covered by a semipermeable fibre membrane, and the two ends are connected to the inlet and outlet tubes of artificial cerebrospinal fluid. The dopamine in human brain passively diffuses across the semipermeable membrane into the artificial cerebrospinal fluid by the exchange of substances in artificial cerebrospinal fluid and in the cerebrospinal fluid. This is a sensitive method, however, unfortunately, it has a low temporal resolution.
Electrochemical method. The first step, the same as the method mentioned above, is to undergo surgery to implant deep-brain stimulation electrodes. The carbon fibre electrodes are placed near the surface of the cells to be recorded, and a certain voltage is applied to the electrodes, which is kept higher than the redox potential of the neurotransmitters to be detected. The fast scan cyclic voltammetry is used with the electrodes to collect the electrical signals for relevant fast dopamine pulse and obtains results after a series of processes and analyses. This method results in a specific detection at the cellular level. However, although the fast-scan cyclic voltammetry has high temporal resolution and certain specificity of neurotransmitter molecules, it is difficult to achieve simultaneous detection of multiple regions.
Molecular imaging, a non-invasive methodology. One important method is positron emission tomography, PET. In this molecular imaging method, a radiolabelled ligand is administered intravenously. Afterwards, the patients are placed in a PET camera, and the data is collected every few seconds while the volunteers perform tasks in the scanner. If the neurotransmitter is released during the scan, the concentration of ligand in the receptor will decrease as it is replaced by the endogenously released neurotransmitter. The dopamine synthesis and the concentration of transporters, which are positively correlated with dopamine cells, can be measured in this way. The test involves injecting a radioactive substance that binds to a dopamine transporter, which can be measured using the camera.
However, the researchers may be more interested in the interpretation of the nature of dopamine dysfunction in schizophrenia by these measurements than by the methods.
In previous studies, both striatal dopamine synthesis capacity and release are found to be elevated in patients with schizophrenia. Clinically, schizophrenia is generally classified as a dopaminergic sub-type and a non-dopaminergic sub-type. For antipsychotic responders, the measure for dopamine via the measure for the dopamine-related enzyme is shown to have a higher level, while indirectly demonstrating psychosis patients have higher dopamine synthesis capacity and the disease is responsive to subsequent antipsychotic treatment. The level of dopamine synthesis and secretion is related to the treatment of schizophrenia. With Voxel-wise analysis, The research of Jauhar et. al demonstrate that the lack of dopamine synthesis is consistent with whether patients respond to the treatments in the clinic has consistency with dopamine dysfunction. For the patients who responded to treatment, there is an increase in dopamine synthesis capacity relative to non-responder. Patients who responded to treatment had increased dopamine synthesis capacity compared with healthy individuals. The classic dopamine hypothesis states that the dopamine dysfunction in the prefrontal cortex leads to negative symptoms in schizophrenia, while dopamine hyperfunction in the mesolimbic pathway leads to positive symptoms. The measurement of dopamine in neuroimaging informs us about the phenomenon of dopamine dysfunction in schizophrenia. And combining with the basis that dopamine signalling is involved in labelling environmental spurs, we can predict that dopamine dysfunction in striatal regions is the main cause of schizophrenia which may lead to functional impairment of striatal regions,
However, our detection techniques for the brain are still not accurate enough, such as we cannot accurately detect receptor and synaptic dopamine levels in vivo. Based on the current level of science and technology, we cannot fully understand the role of the dopamine system in the start and development of schizophrenia. Nevertheless, the dopamine hypothesis is still powerful and relevant. With the continuous increase of human understanding of the brain, targeting this system, the development of new treatments still has great potential and prospects.
