There are very close genetic links between certain psychiatric disorders. We see this in the clinic, when doctors have difficulty identifying a specific illness or discover that a patient with depression also develops anxiety, for example. The boundaries between certain mental disorders and others are sometimes confused during the consultation and this is explained at the molecular level: there exists a sort of relationship genetic and common risk variants between diseases. A new study, published this Wednesday in the journal Nature and based on the analysis of the DNA of more than a million people, he delved into this area and shed light on the molecular thread that connects fifteen mental disorders.
Specifically, this international research found that 14 diseases share, to a greater or lesser extent, genetic risk variants. That is, molecular signals that predispose to the development of these mental conditions. The authors specifically identified five disease groups that have a strong genetic correlation: this occurs, for example, between schizophrenia and bipolar disorder; or between anxiety, depression and post-traumatic stress; or between autism and attention deficit hyperactivity disorder (ADHD). The findings suggest that common genetic marks are closely linked to early stages of brain development and that studying them further could help better understand mental disorders, improve diagnosis and encourage new treatments. This research follows other studies which have already shed light on fragments of these genetic links between brain diseases in recent years. “It’s about unraveling all the pieces of the genetic puzzle to create precision and predictive medicine,” explains Antoni Ramos Quiroga, head of the psychiatry department at Vall d’Hebron Hospital in Barcelona and researcher at the Biomedical Research Center of the Mental Health Network (CIBERSAM). The doctor, who participated in this research and others in the same field, assures that studies like these “will contribute to redefining mental disorders, not only based on symptoms, but also based on genetic variables.”
In this case, the authors identified five categories linking groups of mental illnesses with a high degree of shared genetic risk. Thus, the “compulsive factor” includes in the same group anorexia nervosa, obsessive-compulsive disorder (OCD) and Gilles de la Tourette syndrome; The so-called “internalizing factor” includes depression, anxiety and post-traumatic stress; another category is tandem schizophrenia and bipolar disorder; “neurodevelopmental factor” includes autism and ADHD; and the last category with strong genetic links in common is that of substances of abuse, where addictions to tobacco, alcohol, cannabis and opioids are grouped together. The strongest correlation is seen within each group, but there are also shared genetic signals between conditions in different categories.
“For example, between ADHD and depression there is a high percentage (of shared genetic variants),” illustrates Ramos Quiroga. The results, he insists, coincide with “the clinical reality” observed during the consultation.
These shared genetic signals, explains Ramos Quiroga, are “predisposing factors”. In other words, they increase the risk. But remember that having any of these variables does not mean that a person will develop any of these diseases.
Many genes, but also the environment, are involved in the construction of mental disorders. There is “an interaction between factors”, recalls the psychiatrist from Vall d’Hebron: “There are factors from the beginning that predispose us, but we must also focus on the environment and fight against sexual assault or drug addiction, for example (these circumstances increase the risk of worse mental health)”.
Early stages of brain development
The authors of the article published in Nature They suggest that the identified risk variants play a role in the early stages of brain development. “This tells us that these genetic factors determine the development of the neuronal connection in the brain and that there can be an alteration from the beginning,” reflects Ramos Quiroga.
In a commentary, Abdel Abdellaoui, researcher at the Department of Psychiatry at the University of Amsterdam, also points out: “Across all factors, associated genes show maximum expression during fetal development, highlighting the importance of early developmental processes in psychiatric risk. »
However, Ramos Quiroga asks not to lose sight of the complexity of these disorders and recalls that they are multifactorial: “If you have a susceptibility and you add other factors that increase this susceptibility, it is worse: there are genetic factors that give you more risk and that have to do with brain development, but there are also other variables linked to immunological factors; underlines.
Abdellaoui agrees and emphasizes that these psychiatric disorders seem to occur when “certain combinations of genes and life experiences combine in an unfavorable way.” “This should redefine mental illness not as a biological defect, but as the unfortunate intersection of natural variation and environmental stress,” he says.
Redefining the diagnosis
Abdellaoui, on the other hand, argues that these genetic variants are grouped into five categories “which transcend current diagnostic limits” and wonders if these genetic patterns shared between 14 psychiatric disorders can make us rethink the diagnostic framework of mental illnesses. “Few genetic variants are exclusive to a single diagnosis, suggesting that Diagnostic and Statistical Manual (DSM; the conventional tool for diagnosing psychiatric disorders) categories might be useful clinically, but are apparently arbitrary at the biological level,” he acknowledges.
Francina Fonseca, head of the psychiatry department at the Hospital del Mar in Barcelona, defends that the current classifications continue to be useful because they help professionals understand each other and speak the same language. But he assumes that we must “be self-critical, be humble and rigorous” and try to increasingly refine the diagnoses.
The psychiatrist specifies that this research, in which she did not participate, will not have an immediate impact on clinical practice, but that it will help to better classify these diseases: “In mental health, we do not have laboratory tests or neuroimaging that allow us to diagnose what is happening in the brain. We focus on symptoms, which may be based on the subjectivity of the person experiencing or interpreting them. amended.”
Ramos Quiroga recognizes that this entire line of research “will contribute to having a classification of mental disorders more linked to biological factors” and adds that it also opens the door to the identification of molecular targets on which to develop new drugs.
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