A massive international study with more than one million cases publishes in Nature the most complete genetic map of 14 of the most prevalent psychiatric disorders to date. A map that puts numbers to a reality that psychiatrists around the world have long found in their everyday practice: psychiatric disorders are deeply related, not only in clinical but also in genetics, which greatly complicates differential diagnosis.
From Catalonia, 7 research centers and 3 hospitals contributed to the study, which in total comprises more than one million cases. These are IDIBELL and Bellvitge University Hospital, Vall d’Hebron University Hospital and the Vall d’Hebron Research Institute, the Hospital de Sant Joan de Déu and the Sant Joan de Déu Research Institute, and the Sant Pau Private Foundation, in addition to the UAB and the UB, which made contributions in areas such as eating disorders (EDs), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). At the state level, three groups from the Networked Biomedical Research Center (CIBER-SAM, CIBER-ER and CIBER-OBN) and the University of Santiago de Compostela have also participated.
The study groups the 14 disorders into 5 families according to genetic criteria. All of them share, to a greater or lesser extent, risk genetic markers, but they do so more among disorders within the same group. Thus, for example, anxiety shares more markers with colleagues in the fourth group (internalizing disorders), such as depression and post-traumatic stress disorder, but it also shares some markers with anorexia nervosa and OCD in the first group (compulsive disorders). Thus, a network of cross-genetic relationships between disorders is configured, demonstrating that it is necessary to carry out a transdiagnostic approach to understand and address them better.
Turning the method around: from biological factors to disorders
The study by Nature is presented with a plot twist: the new classification proposal for psychiatric disorders has been made with a different approach, reversing traditional logic. “Instead of going from individual disorders to the biological factors that define them, we have gone the other way: we have analyzed the relationship between biological factors to understand the disorders, and help us to better recognize the similarities and differences between them”, explains Dr. Fernando Fernández-Aranda, clinical coordinator of the TCAs within the study, and leader of the research group in Psychoneurobiology of eating disorders and addictive behaviors at IDIBELL and Bellvitge University Hospital.
Thus, in this study, they have started from the analysis of biological factors, in this case, genetic risk markers, and have compared them with each other, classifying them into five groups due to genetic similarity. By doing so, the disorders associated with risk markers have also naturally been classified in different groups of disorders with high genetic overlap. Some closely related disorders include anorexia nervosa with OCD, ADHD with autism, or depression with PTSD. The most obvious relationship has been seen between schizophrenia and bipolar disorder, which could practically be considered to have twin genetics.
Genetics is just one piece of the puzzle
When talking about shared genetic risk between disorders, it is important not to lose sight of the fact that genetics are not the only piece of the puzzle. They only explain a percentage of the risk of developing a psychiatric disorder, variable in each disorder and particular case.
Thus, for example, the weight of genetics in EDs is around 45%: the remaining 55% of the risk of developing an eating behavior disorder is determined by the environment and, often, despite the genetic risk, an environmental detonator is needed to trigger the disease. In other disorders, genetics have more influence (such as schizophrenia or bipolar disorder) or less (such as anxiety disorders). Environmental factors, personal experiences and the social environment play a decisive role in whether this predisposition ends up manifesting itself.
15 years of international project that are still ongoing
This milestone in the field of psychiatry comes after 15 years of data collection and analysis by the Psychiatric Genomics Consortium, an international consortium with more than 800 researchers involved, from around the world, who aim to describe the genetic architecture of psychiatric disorders in order to apply information in a practical way.
Apart from this task of genetic decoding, they have been working for years on shaping a new way of understanding psychiatric disorders. “The idea is to stop understanding individual psychiatric disorders categorically, putting them in immovable compartments, and to understand them with a dimensional and integral approach,” explains Dr. Fernández-Aranda. “It is a subtle change, but it makes a difference and could help to better understand psychiatric pathology, improve diagnostic approaches and apply precision medicine with new treatments useful for several disorders at the same time,” he adds.
The Bellvitge Biomedical Research Institute (IDIBELL) is a research center created in 2004 and specialized in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles per year. IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the HR Excellence in Research program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL is an Accredited Center of the AECC Scientific Foundation (FCAECC).