Groot onderzoek voegt nieuw bewijs toe aan genetische kaart van psychiatrische stoornissen

Groot onderzoek voegt nieuw bewijs toe aan genetische kaart van psychiatrische stoornissen

maart 11, 2020 0 Door admin


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A new international study of approximately 230,000 patients has identified 109 genetic variants associated with eight psychiatric disorders: autism, attention-deficit/ hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder (OCD) and Tourette Syndrome.

The researchers analyzed the genetic base shared by these disorders and defined three groups of highly genetically-related disorders:

  • those marked by compulsive behaviors (anorexia nervosa, obsessive-compulsive disorder);
  • mood and psychotic disorders (bipolar disorder, major depression and schizophrenia), and;
  • early-onset neurodevelopmental disorders (autism spectrum disorder, ADHD and Tourette syndrome).

The study, published in the journal Cell, adds new evidence to the genetic map of psychiatric conditions.

“Those disorders listed in the same group tend to share more risk genetic factors between them than with other groups. Moreover, we saw that these groups built on the basis of genetic criteria match with the clinical output,” said Dr. Bru Cormand, professor at the Department of Genetics, Microbiology and Statistics and head of the Neurogenetics Research Group at the University of Barcelona in Spain.

“However, the new study does not put emphasis on the genes shared by members of a particular group but on the genes shared by the highest number of disorders.

“That is, those factors that would somehow give way to a ‘sensitive’ brain, more likely to suffer from any psychiatric disorder. And the fact that this could be one or another disorder would depend on specific genetic factors, not forgetting about the environmental factors,” said Cormand.

About 25% of the world population is affected by some type of psychiatric condition that affects intellectual ability, behavior, emotions (affectivity) and social relations. Many psychiatric disorders show comorbidities, and it is quite likely for a patient to show more than one disorder over his/her life.

According to the findings, a gene called the DCC gene, which is related to the development of the nervous system, is a risk factor for all eight studied disorders. Also, the RBFOX1 gene, which regulates the splicing in many genes, is involved in seven out of the eight disorders.

In addition, ADHD and depression share 44% of those genetic risk factors that are common in the general population. Regarding schizophrenia and bipolar disorder, these figures reach 70%.

“These results help people with ADHD so they can understand the disorder and also why they can suffer from depression more frequently,” said researcher Dr. Josep Antoni Ramos-Quiroga.

“Furthermore, this is new scientific evidence that ADHD can persist over life, and be present in adults. We hope this helps to reduce the social stigma regarding ADHD and other mental illnesses.

“We now know this situation regarding psychiatric disorders can be explained, in part, by genetics. Therefore, regarding the case of someone with ADHD, we can estimate the genetic risk to develop other disorders s/he does not suffer from yet — for instance, drug addiction — and take preventive measures if the risk is high. However, these predictions are just probabilistic and not fully deterministic.”

Apart from genomics, the study also looked at the impact of gene expression in space (which organs, specific regions of the brain, tissues and even cells express the disease genes) and in time (in what developmental phase of the individual these activate).

One of the most relevant findings of the study reveals that those genes that are risk factors for more than one disorder are usually active during the second trimester of pregnancy, coinciding with a crucial stage in the development of the nervous system.

Oddly enough, some genetic variations can act as genetic risk factors in a certain disorder but have a protective effect in other cases.

“In the study, we identified eleven areas of the genome in which the effects are opposed in different pairs of disorders; that is, protection in one case, and susceptibility in the other,” said researcher Dr. Raquel Rabionet, from the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB).

“This could make sense in some instances in which there would be a genetic variant with contrary effects in ADHD — a disorder usually related to obesity — and anorexia.

“However, regarding the neurodevelopmental disorders such as autism and schizophrenia, there are genetic variants with opposite effects and others that work in the same direction. This suggests that the genetics of psychiatric disorders is more complex than we thought, and we are still far from solving this puzzle.”

Source: University of Barcelona

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