Is Schizophrenia a Genetic Disorder?

Is Schizophrenia a Genetic Disorder?

If you watched the 2001 thriller Donnie Darko, you probably caught sight of what hallucinations may feel like. In the movie (spoiler alert!), Donni Darko is a teenager who struggles at school and has a problematic relationship with his parents. Donnie suffers from delusions of a wicked rabbit named Frank, predicting that the world will end soon. Donnie attends long therapy sessions, which implies that he suffers from Paranoid schizophrenia. 

The film shows how Donnie’s world was wrecked, and every aspect of his life was impacted. But let’s observe it from a scientific perspective. 

What is Schizophrenia?! And would there be anything the therapist could do to cure it? Could the therapist just point out a magic pill, so Donnie stops having hallucinations and is free from schizophrenia? Or maybe open the genetics book and voila! Find which gene caused Donnie to suffer!

That’s why I invite you to explore with me in this blog post about Schizophrenia, its causes, symptoms and … is schizophrenia a genetic disorder?

What is Schizophrenia?

Schizophrenia is a complex mental disorder that affects how people think, perceive things, and handle emotions and social interactions. Even though schizophrenia’s severity varies among individuals, the way it interferes with a person’s life can be disabling. Schizophrenia is highly heritable (transmissible from parent to offspring), but the genetics are complex.

There is a lot of stigma around schizophrenia and misconception. Schizophrenia does not mean a person with a split personality. Instead, it is a chronic psychotic disorder that disrupts the patient’s thoughts and behaviour, making life challenging and daily tasks difficult to complete.

What causes Schizophrenia?

Although schizophrenia has a long-established history of neurobiological investigation, when talking about the cause of schizophrenia, there is no known “disease mechanism” or identified biological abnormalities leading to the disorder. However, recent genetic findings have shown a link between schizophrenia and early neurodevelopmental events, such as birth trauma. Furthermore, some studies indicated that neurodevelopmental disorders, such as Autism, and ADHD, play a role in the genetic risk associated with schizophrenia. Although these reported cases are still limited, they open a research potential to better understand the origin of schizophrenia. 

What are the Symptoms of Schizophrenia?

Symptoms of Schizophrenia are broken down into three classifications:

• Positive symptoms – added by the presence of the disorder – these include hallucinations; patients actually think that something is real despite evidence that it is imagined.

Delusions; patients may feel, see, hear or smell things that do not exist. And abnormal behaviours that vary in severity; patients may do things that appear strange or meaningless or have unexpected reactions that interfere with their ability to manage their behaviour.

• Negative symptoms – subtracted from the ‘normal’ state by the presence of the disorder – are linked to patients’ emotions and behaviour, such as diminished emotional expression, inability to feel interested in something or pleasure, lack of motivation and social withdrawal.

 • People with schizophrenia also experience cognitive symptoms that degrade the individual’s ability to communicate and include: disorganized speech, thoughts, attention, and impairment of working memory (the way people hold information temporarily and process them).

The Genetics of Schizophrenia

Latest genomic technologies permit researchers to rapidly and inexpensively sequence large gene fragments that provide a thorough examination of someone’s genetic makeup. Geneticists have been comparing genomes for nearly two decades, looking for the dissimilarities that might explain why some people develop a particular disease over others. These dissimilarities are called variations. Each individual carries many genetic variations – generally single-letter DNA modifications. Understanding which of these variations contributes to disease and how they function is a great challenge. However, there has been scientific evidence supporting the idea that genetic factors play an important role in the causation of schizophrenia. Studies consistently show that the risk of developing the illness increases when there is a family history of schizophrenia. Also, it is higher in the case of twins and children of both parents with schizophrenia.

Multiple types of mutations have been linked to schizophrenia. For example, in a study that included a large sample of cases, a deletion in a specific gene was associated with 0.3% of diagnosed patients with schizophrenia. In addition, deletions and duplications of the genetic material that has been associated with neurodevelopmental diseases were also linked to schizophrenia. Furthermore, new mutations have been reported recently, were associated with schizophrenia, called de novo (means; new) mutations. The repeated reports of the de novo mutations suggest that the number of genes related to schizophrenia is large. This is where the complexity of schizophrenia comes from.

Is Schizophrenia a genetic disorder?

Schizophrenia is a polygenic (poly: many, genic: genes) disorder, meaning that a large number of genetic variants are involved in it. A genome-wide association study (GWAS) – a method used in genetics investigation to associate specific genetic variations with certain diseases – allows the identification of such variants. In addition, researchers have developed tools to calculate which variants tend to be found more often in groups of individuals with a given disease. And these variants can be hundreds or thousands per disease.

Researchers run genomic data collected through the GWAS on a computer. Then, using statistics, they can estimate how a set of an individual’s variants affects their risk for a particular disease. This generates a polygenic risk score and can be done without previous knowledge of the genes involved in a given complex disease. When using the polygenic risk score for schizophrenia, studies showed an overlap of the genetic variants for schizophrenia, attention-deficit hyperactivity disorder (ADHD), Bipolar disorder (BD), autism and major depressive disorder (MDD). However, the strongest overlap was shown between schizophrenia, BD and MDD. This means that genetic variants associated with schizophrenia are also found in BD, ADHD and MDD. And a person with schizophrenia is susceptible to developing BD and MDD, but this is not definite. Because polygenic risk score measures the correlation and not the causation of a disorder. 

Schizophrenia is a complex disease that disrupts a person’s thoughts, emotions and social life. The severity of the disorder varies and can be disabling. Despite years of research, there is no known cause for schizophrenia. However, cutting-edge technologies and advanced genetics research allowed researchers to better understand schizophrenia. Also, findings have shown that the risk of schizophrenia may be associated with early neurodevelopmental diseases. Moreover, genetic variants involved in schizophrenia were also reported in bipolar disorder and major depressive disorder, suggesting that early neuropsychiatric disorders impact the genetic risk of schizophrenia. 

Hopefully, the world is moving towards fighting the stigma around mental health. However, more scientific evidence is needed to support creating inclusivity and normalising treatment for mental disorders just as it works for physical diseases. 

Back to Donnie – I would like to hear from you… What would you think would have been different for Donnie if more awareness about his disorder was more present in his community?