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Genetic Clusters Suggest Schizophrenia Is 8 Distinct Diseases

A recent discovery has shown that the serious mental illness that is schizophrenia is actually a group of 8 distinct genetic disorders. Although genetic research has been difficult for those involved in the field of mental health, it is the future of all medicine and humanity. Simply altering neurotransmitters with drugs is a short term solution that will only lead limited results.

In order to actually discover a cure or a treatment that actually works, we need to better discover the underlying genetic mechanisms behind schizophrenia. Most people are aware that there are currently 5 types of schizophrenia, each with distinct sets of symptoms. Researchers are attempting to pinpoint the genetic etiology of the illness.

Schizophrenia and Genetics: 8 Different Diseases Based on “Clusters”

Research discovered that clusters of genes are different among individuals with schizophrenia. However, even among those with schizophrenia, the genetic clusters tend to be one of eight types. Additionally of these eight types, someone could experience a more severe or less severe case of the illness. So there could be two individuals with paranoid schizophrenia, but one may be significantly more impaired in regards to functioning than the other.

The individual who was more impaired will likely show stronger genetic links to that particular subtype. Now researchers know that saying someone has “schizophrenia” is really too broad of a diagnosis. Saying someone has schizophrenia is like saying that someone is “injured” so let’s give them medication. In regards to the “injury” analogy we don’t know whether the injury is minor, moderate, severe, or what specifically is injured.

All we know is that pain medication can help ease symptoms (or in the case of schizophrenia, antipsychotics) so that’s what is prescribed. Newer research helps us understand that those with schizophrenia could have one of eight separate problems. Using the injury analogy, we now know that the person could have a leg injury, back injury, hand injury, shoulder injury, etc. – each to a different degree. This is why some people may struggle more with positive symptoms, negative symptoms, and/or cognitive symptoms.

Schizophrenia and Genetics: Establishing The Links

In the study, researchers found that some people had a higher risk of schizophrenia based on their DNA. The study involved comparing 4,200 people that were formally diagnosed with schizophrenia to 3,800 individuals without mental illness. A specific set of genetic changes was associated with a 95% chance of developing schizophrenia. Although it is unknown what causes schizophrenia in all cases, in nearly every case, maladaptive genetics play a role in its development.

A woman in the study is highlighted as having demonstrated signs of schizophrenia at just 5 years old. As a child, this woman was hearing voices and ended up believing that her dolls kept calling her name. Another case involved an individual with a genetic profile indicating that she had a 71% of developing schizophrenia. This person experienced symptoms of a more common mental illness and at 17 years of age, this individual had auditory hallucinations.

Author of the study Robert Cloninger has stated that a majority of people have less than a 1% chance of developing schizophrenia. Obviously if you share a first-degree relative with the disease, your risk of developing schizophrenia drastically increases. If your identical twin has schizophrenia, the risk of you developing the same disease is approximately 80%.

Unfortunately, most doctors continue to diagnose schizophrenia with methods that aren’t particularly accurate. As more information is released regarding genetic findings and tests can be conducted, doctors will have better tools to assess the accuracy of schizophrenia diagnoses. In response to the study, Psychiatrist Stephen Marder issued the statement that, “The way we diagnose schizophrenia is relatively primitive.”

The difference between this research and findings in the past is that past research attempted to isolate a single gene that could be causing the disease. Current research has found that it’s not caused by a “single” gene, rather specific changes in genetic clusters that lead to symptoms. The new research suggests that the genes function together like winning or losing poker hands. Even among those with schizophrenia, some individuals tend to have been “dealt” worse genetics than others.

This is why there are individuals with more severe symptoms and others who are considered high-functioning and better able to manage their disease. For some unfortunate individuals, their genetic profiles indicate nearly a 100% risk of developing schizophrenia. In other words, these genetics would be analogous to being dealt the worst possible combination in a 5-card draw game of poker – nearly a guaranteed loss (e.g. high card seven, no same cards, no straight or flush).

Why these genetic findings are important…

Evidently the genetics behind schizophrenia are actually “schizophrenic.” As we continue to get a better understanding of the specifics behind this disease, we can address each one on an individual basis. Additionally diagnoses can be made more accurate, with better treatment options, and more personalized psychiatric care. In the far future, these findings could one day even lead to a cure.

  • Addressing each of the 8 diseases: The biggest finding from this study was that schizophrenia is not one disease like we previously thought. Instead it is eight distinct genetic subtypes, each that result in different symptoms. By knowing that there are eight separate diseases, this should allow researchers to devise treatments for each specific one.
  • Diagnosis: The findings will eventually help doctors make more accurate diagnoses of schizophrenia. Currently the diagnostic criteria is specific for each criteria, but it can be difficult to correctly diagnose this illness. Now that researchers know what genetic variants to look for, they will be able to demonstrate links between specific genetic changes and the “eight” types of schizophrenia.  In the past, the mainstream thought was that all types of schizophrenia shared similar diagnoses. This finding shows that each of the eight genetic differences should be considered separate diagnoses. It is hoped that patients with schizophrenia can have their genetics analyzed for a more accurate diagnosis. Additionally, this should help prevent the malpractice associated with misdiagnoses from psychiatrists.
  • Treatment: Since we now know that there are eight genetic subtypes of schizophrenia, it may open up new doors for researchers to address each one. Currently the treatment options (antipsychotics) for those with schizophrenia are considered very poor in terms of long-term effects. Antipsychotic medications are akin to dropping an atomic bomb inside the brain to address symptoms instead of using a smart bomb to only target certain features.  An atomic bomb may help symptoms, but it is also going to do a lot of other damage. A smart bomb type drug could be used to target each of the eight types of schizophrenia on an individual basis. Most pharmaceutical companies are essentially creating chemicals that they know will alleviate symptoms, but problems created by the drug can be just as bad (or worse) than the underlying symptoms – creating a catch-22 situation for the patient.  Previously it was thought that all types of schizophrenia stemmed from the same underlying problem. As it appears, each could actually be diagnosed separately. The separate diagnoses and differences between them demonstrate that we currently lack the treatment specificity to address each one. Rather we typically treat them with antipsychotic medications, which is analogous to using duct tape to temporarily fix eight separate problems.
  • Personalized care: A new era of psychiatric care is slowly emerging which will eventually involve people receiving a personalized diagnosis along with personalized treatments. Since a person will have 1/8 types of schizophrenia, and the specific subtype will vary in severity, a doctor will be able to determine what treatments (i.e. medications and dosages) will work best to address symptoms.
  • Specificity: Since we know that schizophrenia is now eight separate diseases, we will be able to identify more specific aspects of each disease. By identifying more specifics, it will be easier to get a better understanding of how each disease works and how to manage symptoms.
  • Future cures: Although there may not be a cure for schizophrenia in our lifetime, there will eventually be one. The cure is going to involve genetic modifications to correct the dysfunctional genetic clusters. We are likely a long ways away from accomplishing this, but in the meantime, there is at least some hope that drugs better than the (arguably pathetic) antipsychotics are developed.

Determinism: Schizophrenia, Genetics, and Environment

Researchers suggest that if someone is dealt bad genetic “cards,” they could have nearly a 100% risk of developing the disease no matter how healthy they are or what they do. This sheds light on genetic determinism, showing that there is actually significant merit to this belief. Being told that you are 100% going to develop schizophrenia based on your genetics could be frightening, but on the same token, could be beneficial in that the problem can be addressed earlier, with potentially improved long-term prognoses.

It still remains a mystery as to why someone with genetics indicating a 70% risk of the disease go on to develop it, while others don’t. This suggests that among individuals who are genetically “at risk” could influence their outcome by nutrition, diet, stress, and social support. In other words, if you are “at moderate risk” (e.g. 50%) but live a very healthy lifestyle with minimal stress, you could reduce your chances of triggering the development of schizophrenia.

Another benefit associated with this finding is that it may encourage more specific research of common diseases. In fact, some would suggest that they should conduct studies like this for nearly every misunderstood disease to get a better understanding of the genetic alterations. I’d be willing to guess that they could get considerably more specific for other mental illness such as depression and anxiety – possibly finding that each could actually be a mix of certain genetic clusters, each to varying degrees of intensity.

Old school thinking involved looking for one gene that may be the “holy grail” in causing a disease to develop. Now we know that for complex diseases like schizophrenia, the “holy grail” isn’t really one gene, it’s the interplay between genetic clusters. Diseases that are caused by a single gene typically don’t affect as many individuals, however diseases influenced by genetic combinations tend to affect a lot of people (e.g. cancer).

These findings are already extremely beneficial because they show us that changes in specific genetic clusters lead to specific symptoms of schizophrenia. People with one genetic cluster may end up with disorganized schizophrenia characterized by grossly disorganized behavior and thinking, while another may end up with undifferentiated schizophrenia – not fitting a clear set of symptoms.

All I can really think is it’s about time more emphasis was placed on genetic research. Instead of throwing money at pharmaceutical companies and having them essentially take educated guesses at what neurotransmitters to target, we can get to the real root of the problem – a person’s genetics.

  • Source: http://ajp.psychiatryonline.org/article.aspx?articleID=1906049

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