Scientists have been studying schizophrenia for a very long time. Nevertheless, it remains the most mysterious mental illness, the early stage of which consists of one or more episodes with psychotic symptoms, and the subsequent stage is marked by an acute mental disorder, when a person has hallucinations and loses a sense of reality. The World Health Organization (WHO) estimates that approximately one in 300 people on our planet suffers from schizophrenia. But even experienced experts do not know what is happening in the brain of such a patient, why the disease occurs and how to treat it.
“Our knowledge of schizophrenia is close to zero,” says Stephan Ripke, a scientist at Berlin’s Charité University Complex and co-author of one of two papers published in the scientific journal Nature. These articles contain research findings that could expand the basic knowledge of schizophrenia and possibly give the green light to the development of medications that are tailored to the individual patient. The fact is that Ripke and other members of an international team of scientists made a discovery that became revolutionary in terms of the biological understanding of schizophrenia. They found at least ten gene mutations that have a strong impact on the likelihood of developing the disease. However, 120 other mutations can also play a key role here.
Towards a New Method of Treatment
Schizophrenia usually occurs in patients in late adolescence or early adulthood. By studying the environmental aspects of the disease, the researchers found that the mother’s diet during pregnancy, the place where a person lives during their growing up, and the use of marijuana during adolescence, all can play a role in the development of the disease.
However, when conducting new studies, scientists did not focus on such factors, but focused on the study of the biological processes involved in the development of schizophrenia.
As Ripke notes, on the one hand, the detection of gene mutations will not facilitate the early diagnosis of patients with schizophrenia. On the other hand, it will make it easier for researchers to assess the risk of the disease and make it more effective to treat it with drugs.
To improve medical treatment
According to Ripke, currently available schizophrenia drugs do not eliminate the actual cause of the disease, but only alleviate its symptoms. These medicines are still being made based on a discovery made over seven decades ago. The first antipsychotic drug was developed in 1950, chlorpromazine, which is still prescribed today for schizophrenia. Chlorpromazine blocks human dopamine receptors. There are other antipsychotics, but they all work in a similar way to chlorpromazine.
Chlorpromazine was originally developed as an anesthetic. Its use in psychiatry happened by accident – after doctors suddenly discovered that the drug could prevent hallucinations in patients in psychiatric clinics.
According to Ripke, with the additional knowledge obtained by scientists about what happens in the human brain during the development of schizophrenia, in the future it will be possible to develop more effective drugs to treat it.
120 genes can influence the development of the disease
Two papers based on two studies and published in the journal Nature look at the genetics of schizophrenia from two different angles. The first study was carried out by the Psychiatric Genomics Consortium (PGC), led by scientists from Cardiff University in the UK. In this experiment, scientists, in order to find a specific genetic change that increases the risk of developing schizophrenia, took a very broad approach, studying the entire genome, that is, the entire genetic material of the body.
After analyzing the DNA of about 77,000 people with schizophrenia and about 244,000 people without schizophrenia, they found almost 300 regions of the genome that are genetically linked to the risk of developing schizophrenia. In these areas, they discovered 120 genes that may play a role in the development of the disease.
Scientists have concluded that the risk of developing schizophrenia depends only on the brain and genes that are concentrated in neurons – brain cells that ensure the transmission of messages from the outside world to the brain and vice versa, which allows people to move and speak. This process is facilitated by synapses that connect neurons to other cells in the brain and body.
Neurons and synapses play a key role
Another study used a more limited approach, but its results suggest that neurons and synapses play a key role in the risk of developing schizophrenia.
This study was conducted by the SCHEMA team, a research consortium led by the Broad Institute of the Massachusetts Institute of Technology and Harvard University. The researchers found ten genes with rare mutations that seem to increase the risk of developing schizophrenia, and 22 other mutations that may also play a significant role.
“In general, a person’s lifetime chance of getting schizophrenia is about one percent. But if you have one of these mutations, the chance increases to 10, 20 and even 50 percent,” said Benjamin Neal, co-author of SCHEMA and member of PGC.
Some of these genes point to problems with synapses as a possible cause of the disease. Scientists at the Broad Institute first discovered this during one study in 2016. In their scientific work, they linked the origin of schizophrenia to specific gene variants for the first time. It also explains why schizophrenia develops during adolescence and early adulthood.
Instead of studying the entire genome, the SCHEMA researchers specifically studied a small part of the genome, the so-called “exome”. Exome codes for proteins. Using the exomes of about 24,000 people with schizophrenia and about 97,000 people without schizophrenia, the scientists looked for variants that affect the gene’s ability to form functioning proteins. Two of the ten gene mutations found by the SCHEMA team were associated with synaptic dysfunction.
At the same time, as the scientists point out, the other eight genes have never been associated with brain dysfunction or specific neuronal function. And this means that there is still a lot to be clarified.
Language as a key to diagnosis
It has been scientifically proven that schizophrenia is inherited in 60-80 percent of cases. Otherwise, we know very little about the genetics of this disease. This is due to a number of problems that are common not only to schizophrenia, but also to many other mental illnesses, such as bipolar disorder or borderline personality disorder, Ripke explains.
According to this German scientist, there is no way to study the disease on animals – because they are not able to talk about the hallucinations they experience and generally describe their condition. And language plays a major role in the diagnosis and subsequent study of schizophrenia. In addition, schizophrenia cannot be diagnosed by a blood test or a brain scan. And it is impossible to take for analysis the brain cells of a patient with schizophrenia, because it is a living organ.
However, the researchers say the extensive DNA sequencing experiments currently underway offer a much better chance of developing drugs that address the root of the problem, not just symptoms like hallucinations. But this requires people who are willing to voluntarily participate in scientific experiments, says Ripke.
“Our research would never have been possible if we had not been trusted by the thousands of patients who provided their genetic data. And we are eternally grateful to all these people,” emphasizes Stefan Ripke, a scientist from the Charité University Complex in Berlin.