“Genetic cause” isn’t as simple as it sounds: reviewing the causes of common neurological diseases
- Thomas Guevara Chacón
- 8 hours ago
- 5 min read
Neurological diseases are disorders that are specially difficult for the general population to understand, but they are often even more complicated to explain for scientists and treating physicians.
In general, we can make two broad distinctions between these diseases: inherited and acquired. The former has genetic and epigenetic causes and are the result of one or more pathological variations and SNPs (single nucleotide polymorphisms, small “mutations” that everybody has and makes their genetic code unique). while the latter are the consequence of previous diseases. In this article, we will refer almost exclusively to the first broad distinction.
The next major distinction we could make is between systemic pathological diseases, i.e., those that cause effects that are not limited to the central nervous system, diseases or injuries that cause side effects such as quadriplegia, loss of the ability to speak, write, or perform activities of daily living in general. Note that this category does not include conditions that may have extra-systemic side effects, such as epilepsy.
There is an avid debate in the biomedical research community about a very major part of this, but it has been always known that the diseases mentioned here have a genetic basis. Today we will explore the reason it isn’t that simple.
First, we have dementias. We will analyze Alzheimer's disease alongside schizophrenia, which, although already well classified as a disorder corresponding to the psychiatric specialty, we must remember that much of its pathophysiology and semiology is purely neurological. In other words, even though it is a disorder that is reviewed in another specialty, we can attribute its causes and effects to purely neurological qualities. In this case, we will specifically review how genetics affects these so-called causes and effects, for which we will review the role of epigenetic factors, SNPs, and pathological variations (formerly known as mutations) as causes of these diseases.
According to recent research, Alzheimer's cannot be explained simply as “genetic”; its causes encompass very specific but well-known conditions such as lifestyle, diet, and environment. However, we have discovered that these factors occur through something called epigenetic interaction. They change DNA in a non-literal way; it is not that they cause pathological variations, but rather that they modify the chemical structure of the genetic code in a way that we can only detect with cutting-edge techniques such as bisulfite sequencing or ChIP-seq to detect histone modifications.
So, we could say that Alzheimer's is a very contextual disease; people of different profiles and health conditions can develop the disease, but we know that by maintaining a healthy lifestyle, particularly by completely or largely avoiding exposure to industrial compounds and heavy metals, we not only do our cognitive health a favor, but we also reduce our chances of developing dementia.
Now, schizophrenia is a complex disorder, but we can resume it greatly by saying that not only does it involve factors similar to those we already mentioned with Alzheimer's, but it also has a social and psychological component that, for the sake of brevity, we will leave for another time. In summary, we have another disease that falls into a category where it shares the character of a dementia even though it cannot be completely put alongside diseases like Alzheimer, but the thing they do have in common is that both of it are extremely contextual, only that it is applied to the order of neurodevelopment. We are dealing with a disease that grows with the person, molds itself to them, and despite being treatable and perfectly controllable, is often minimized or simplified out of fear or ignorance.
I would even like to point out that at Shanghai University they are developing treatment methods for this condition that are not only surprising but also effective, setting a precedent in translational psychiatry, but, returning to the subject at hand, schizophrenia falls into a deeper category of contextual, it has been demonstrated that SNPs represent something called a “polygenic risk”, there is a correlation between this micro differentiations of the genome that can potentially affect the way a person suffers from this kind of diseases, ranging from a light chemical imbalance to a full biochemical crisis that constantly triggers psychotic attacks.
We have historically treated epilepsy as a disease resulting from a failure in sodium-potassium channels, but new research reveals that it appears to be a failure in epigenetic regulators. Epilepsy transcends a simple error to a system failure in the basic code of human existence. To put it metaphorically, the base of the code is corrupted because enzymes such as DNA methyltransferases add marks to the DNA, proteins remove those marks, and then those marks are misinterpreted. A single failure in the system and the genetic message is “poorly written” from the outset. We have also been able to identify pediatric epilepsy as a disorder that usually occurs as a result of de novo variants, meaning that they are often created in the carrier for the first time, which increasingly disconnects epilepsy from being a simple genetic transmission disorder.
To sum up everything we have said so far, many genetic diseases are not as simple as the typical example of Mendelian genetics regarding eye color or hair type. They depend on factors that only today's science has been able to identify as the cause of these diseases, allowing us to begin developing specific and effective treatments that attack the root of the problem and avoid the medical cliché of treating the symptoms rather than the cause of the symptoms.
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