These are the mental disorders that originate in the mother's womb

BarcelonaMost mental disorders appear in adolescence, when the brain undergoes the most significant changes in its maturation process. However, their origin lies during brain development, in the mother's womb. An international team of researchers, including a Catalan presence, has discovered that many of the genes associated with autism, bipolar disorder, and depression are already functional during the initial stages of fetal development, during the creation of neurons. These genes are also linked to neurodegenerative diseases such as Alzheimer's and Parkinson's. The conclusions of the collaborative study between the Hospital del Mar Research Institute and Yale University were published this Friday in the scientific journal Nature Communications.

Most studies that focus on the study of genes involved in mental disorders and neurodegenerative diseases use cohorts of adult patients for their analysis. In this case, the researchers have used a list of around 3,000 genes linked to mental disorders and neurodegenerative diseases, simulating the effect of their alteration on the cells involved in brain development. This stage of brain development is very difficult to study, so they have combined multiple data from human and mouse brains, as well as cellular models in the laboratory.

During the study, the authors have recreated the regulatory networks of each type of cell involved in brain development with the aim of studying what effect they had when they activated or deactivated a gene linked to a mental disorder. In this way, they could determine the weight of the role of each of them. The list of diseases and disorders that can be associated with these genes ranges from microcephaly and hydrocephalus to autism, depression, bipolar disorder, anorexia, schizophrenia, Alzheimer's, and Parkinson's.

Personalized Therapy

Thus, the research places the origin of these diseases and disorders in very early stages of brain formation in the fetus, earlier than previously recognized. In all of them, they have found genes involved that are already functional in the earliest stages of brain development, when neural stem cells build the brain. Xoel Mato-Blanco, a researcher at the Hospital del Mar Research Institute, explains that they have also identified "time windows and cell types where the action of these genes is most relevant," that is, they have found when and where they should act to prevent the function of these genes.

According to the authors, having this information is useful for understanding the origin of diseases that affect the cerebral cortex, that is, how genetic alterations translate into these pathologies. Understanding these mechanisms, the role of each gene in each disease, can help develop targeted therapies that act on them, generating opportunities for gene therapy and personalized treatments.