March 4, 2019Psychiatry
Neuromelanin is a dark pigment created within dopamine neurons of the midbrain -- particularly in the substantia nigra, a brain area that plays a role in reward and movement. Neuromelanin accumulates over the lifespan and is only cleared away from cells following cell death, as occurs in neurodegenerative disorders such as Parkinson's disease. It has been shown that a type of magnetic resonance imaging, neuromelanin-sensitive MRI (NM-MRI), is lower in the substantia nigra of people with Parkinson's disease, reflecting the cell death that occurs in these patients.
According to an article published in the Proceedings of the National Academy of Sciences (19 February 2019), a new biomarker has been identified as a potential indicator for psychosis. The study showed NM-MRI is a potential biomarker for psychosis, as it was found to be a marker of dopamine function, and an indicator of the severity of psychotic symptoms, in people with schizophrenia.
Despite the utility of this tool for detecting neuron loss in neurodegenerative illnesses, NM-MRI had not yet been shown to provide a marker of dopamine function, nor had its utility been demonstrated in individuals without neurodegenerative illnesses. In this study, the authors conducted a series of validation studies to show that NM-MRI can serve as a marker of dopamine function in individuals without neurodegenerative disorders. According to the authors, the main advantages of this technique are that, compared to other established and more direct measures of dopamine function, neuromelanin-sensitive MRI does not involve radiation or invasive procedures. The authors added that this advantage makes it more suitable for pediatric populations and for repeated scanning, which could be useful to monitor the progression of illness or response to treatment. It only takes a short scan that could be implemented in most clinical scanners, and it affords a very high anatomical resolution compared with PET measures, which is important to examine functions or dysfunctions of specific parts of the substantia nigra.
For the study, the authors first set out to determine whether NM-MRI could accurately detect regional variations in the concentration of neuromelanin in those without neurodegeneration of the substantia nigra. To examine the detection ability of NM-MRI, the authors compared NM-MRI measurements of neuromelanin to chemical measurements of neuromelanin in post-mortem brain tissue. Results showed that across all sections of tissue, that higher NM-MRI signal was associated with higher concentrations of neuromelanin. The results confirmed, for the first time, the ability of NM-MRI to measure regional concentrations of neuromelanin. Furthermore, the results showed that NM-MRI signal reflects concentrations of neuromelanin in tissue, rather than just the number of neuromelanin-containing neurons. The authors next sought to determine whether NM-MRI could capture variations in neuromelanin in smaller anatomical subregions within the substantia nigra. Since dopamine function is thought to differ significantly in different parts of the substantia nigra, there was a need to determine the ability of this tool to capture these anatomical differences. So, the research team examined NM-MRI data from patients diagnosed with Parkinson's disease and individuals without Parkinson's disease. Results showed decreases in NM-MRI signal in those with Parkinson's disease in the lateral, posterior, and ventral areas of the substantia nigra - findings that correspond to the known anatomical distribution of cell loss in this brain area in Parkinson's disease. These results confirmed that NM-MRI can capture known topographical variability within this brain structure.
A next critical step was to show a connection between NM-MRI and dopamine function. To accomplish this, the authors collected measurements of dopamine release capacity (as measured using positron emission tomography (PET)) and NM-MRI data from people without neurodegenerative illnesses. Results showed that individuals with a higher NM-MRI signal had greater dopamine release capacity in the striatum (a core component of reward, motor, and cognitive systems). The authors also found that NM-MRI signal in the substantia nigra was associated with functional MRI measures of regional cerebral blood flow.
Lastly, the authors examined the link between NM-MRI signal and psychosis severity, finding that more severe symptoms of psychosis were associated with higher NM-MRI signals in the nigrostriatal pathway of individuals with schizophrenia and in those at-risk for schizophrenia. Since psychosis is associated with dopamine system dysfunction, characterized by greater dopamine release and synthesis capacity in the striatum, the findings suggest that NM-MRI is capturing this dopamine dysfunction, supporting the role of NM-MRI as a potential biomarker for psychosis.
The authors concluded that the findings validate the use of NM-MRI in populations beyond those with neurodegenerative disorders, showing it can serve as a measure of neuromelanin concentration and dopamine function in the substantia nigra.