The Neuroscience of Schizophrenia: a Focus on Oligodendrocytes
Author: Nicole Yu (MSc Cognitive Neuroscience, UCL)
Schizophrenia is defined as a mental health condition with a range of psychological symptoms including hallucinations, delusions, and overall difficulties in distinguishing between what’s happening in their heads and reality. It is a disorder that some people may have learned of through its portrayal on the big screen, through movies such as A Beautiful Mind (starring Russell Crowe), The Soloist (starring Jamie Foxx and Robert Downey Jr.), and Keane(starring Damian Lewis). The first two movies are based on the real lives of geniuses that had schizophrenia: John Nash, Nobel Prize-winning mathematician and economist, and Nathaniel Ayers, skilled musician. Keane is about a character who has schizophrenia and develops addiction to alcohol and drugs.
From movies such as these however, there can be some misconceptions of the disorder. For example, although the first two movies are based on real people, there could be the misconception that schizophrenia occurs commonly in people with high levels of intellect or talent when this is not necessarily the case. Another misconception that people may gain from a movie like Keaneis that those with schizophrenia often develop drug and alcohol abuse, and may even become violent, when again this is not necessarily true.
These are just examples of how the disorder could be misunderstood by the general population. However, it is not only important for schizophrenia to be understood in better ways by the general public but in research as well, and more effort has been put in to better understand its underpinnings. Emerging research has discovered an interesting target of research - oligodendrocytes.
Firstly, what are oligodendrocytes? They are a type of glial cell that are known to produce the myelin sheaths (a wrapping around nerve cell fibers which insulates and helps improve electrical transmissions) in the central nervous system. The term myelination, which comes from myelin sheaths, refers to the process of acquiring them. White matter that you see in the brain contains oligodendrocytes. Interestingly, there are oligodendrocytes found in grey matter as well, and this is because while they do primarily form myelin sheaths, they have other functions too.
The most commonly known condition associated with oligodendrocytes is perhaps multiple sclerosis, which involves demyelination that leads to inflammation in the central nervous system. Oligodendrocytes are not as well associated with schizophrenia, although recent studies have also linked schizophrenia to abnormalities in myelination and white matter.
To begin, researchers used MRI to establish structural evidence of abnormalities in myelination. This was shown in one study where there was a significant decrease in myelin water fraction (in other words as seen in an MRI scan : less white, more black) in those with chronic schizophrenia as compared to those with just a first-episode of psychosis and healthy individuals. You can see from the picture below just how noticeable the difference is!
The next line of evidence came from genetic studies conducted on post-mortem brains of those with schizophrenia. It has been found that there are severe downregulations in the genes related to myelin and oligodendrocytes in these brains as compared to healthy individuals. Additionally, big reductions in the proteins that initiate and maintain these oligodendrocyte-related genes were seen. And so, a strong genetic component to oligogendrocytes in schizophrenia has been established.
Now that we have structural and genetic evidence linking myelin abnormalities and the disease, the next step could be to study this with a clinical component. This is what some studies have tried to do. Myelin has been used as a biomarker for clinical symptoms following research that compared white matter volume to symptoms as measured by a clinical rating scale typically used on individuals with schizophrenia. The negative symptoms of schizophrenia (which include apathy, anhedonia, social withdrawal, and others) were especially linked to reduced white matter volume.
What can we take away from this? Besides the profound discovery of abnormalities in oligodendrocytic function in schizophrenia, this teaches us how important it is to continue trying to spot as many brain abnormalities as possible in any disease of the brain. In order to increase the chances of effectively treating disease where the current underpinnings of which are relatively unknown, such as schizophrenia, there should be more of a research focus on promising new areas. All of this will undoubtedly help our understanding of commonly misunderstood diseases. So, the next time you watch a movie about a certain brain disorder, think twice about what is being shown to you and understand that there is always more to the picture than it seems!
References in case you’re interested in reading further:
Flynn, S. W., Lang, D. J., Mackay, A. L., Goghari, V., Vavasour, I. M., Whittall, K. P., . . . Honer, W. G. (2003). Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Molecular Psychiatry, 8(9), 811-820.
Nakamura, K., Kawasaki, Y., Takahashi, T., Furuichi, A., Noguchi, K., Seto, H., & Suzuki, M. (2012). Reduced white matter fractional anisotropy and clinical symptoms in schizophrenia: A voxel-based diffusion tensor imaging study. Psychiatry Research: Neuroimaging, 202(3), 233-238.
Tkachev, D., Mimmack, M. L., Ryan, M. M., Wayland, M., Freeman, T., Jones, P. B., . . . Bahn, S. (2003). Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. The Lancet, 362(9386), 798-805.
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