American experts in psychiatric genetics have made a breakthrough in understanding the biological nature of schizophrenia and confirm earlier the assumption that the basis of the disease is not the mutations in individual genes, but the complex cross-links of many genes.
As a result, it turned out that in the case of schizophrenia, it is not about one disease, but about eight genetically different diseases, each of which has its own set of symptoms. This discovery, according to the authors, can radically change the approach to diagnosis and therapy of these disorders. The work was published on September 15th on The American Journal of Psychiatry.
Schizophrenia is a mental disorder that is accompanied by hallucinations, delusions, manias, social dysfunction, and emotional problems. As a therapy, antipsychotic drugs are commonly used, but the treatment options are limited due to the still unclear biological basis of the disease. It is known that in the development of schizophrenia a very important role (up to 80 percent) is played by hereditary predisposition. In addition, recent studies of genetic origins of the disease have revealed more than one hundred genomic sites associated with schizophrenia.
"Genes do not work alone," said Robert Cloninger, professor at the University of Washington School of Medicine in St. Louis, USA, one of the leading authors of a new study on the molecular nature of schizophrenia. Function as an orchestra, and to understand how the symphony is sung by them, it is not enough to know the composition of musicians, it is necessary to understand how the scores performed by each other interact with each other. We were able to find out how genes influence each other, why Performed by this orchestra of music or the harmonious and leads to mental health, or destructive and leads to disruption of the structure and function of the brain."
The Cloninger team studied the genomes of 4,200 patients with schizophrenia and 3800 healthy controls in order to detect the relationship between individual variations in the DNA structure, their interaction with each other and the manifestations of the disease in each particular case. As a whole, about 700,000 genome sites were analyzed that contained cases of single-nucleotide polymorphism (SNP) - distinctions in a DNA sequence of one nucleotide. All SNPs were grouped on the basis of relationship with each other and correlation with the risk of schizophrenia. Patients were also divided into groups according to the types and severity of the symptoms present - for example, with different hallucinations and delusions, speech and behavioral disorders.
Professor Robert Cloninger. Photo from news.wustl.edu
As a result, 42 clusters of interrelated SNPs associated with an extremely high probability of development of the disease were detected. It was found that different groups of symptoms have a different genetic background, which allowed the division of schizophrenia into eight diseases, qualitatively differing in clinical manifestations and their severity. For example, in a group of patients with hallucinations and delusions, these symptoms were associated with a network of interacting SNPs, different from those found in the group with speech and behavior disorders. Associated with these different clusters of genetic variations, the risk of developing a particular form of schizophrenia also turned out to be different - from 70 to 100 percent, which means the actual inability to escape the disease for the carrier of such a combination of SNP.
The Cloning Group managed to confirm the findings in two additional studies, the basis of which were large bases of genetic data of patients with schizophrenia, which indicates not only the correctness of the conclusions drawn, but also the need to re-approach the diagnosis and treatment of schizophrenic disorders in a new way. As one of the Cloning's collaborators, Igor Zwir noted, understanding the relationship between individual clinical manifestations and the group of genetic variations behind them should lead to sight-action precisely on those specific signaling pathways that cause violations in each particular Case.
Professor Cloninger, in turn, believes that the basis of other equally common and equally complex in its genetic nature of the disease are the same principles found by him and his colleagues as the basis of schizophrenia. "Attempts I associate such illnesses, as cardiovascular disease or diabetes, malfunction of any individual genes produce results disappointing - said Klonindzher. - Differences in the severity of clinical manifestations of these diseases so far have not found a clear explanation. However, if you try this link Phenomenon of different ymi groups of genetic variation, it could fundamentally change the view of the causes of complex diseases."