Psychiatric Disorders share a new underlying genetic basis

Posted on: 22 June 2018

Psychiatric disorders such as schizophrenia and bipolar disorder often run in families.  A new international study led by researchers at Trinity College Dublin and at the Broad Institute of MIT and Harvard explored the genetic connections between these and other disorders of the brain at a scale that far eclipses previous work on the subject.  The team determined that psychiatric disorders share many genetic variants, while neurological disorders (such as Parkinson’s or Alzheimer’s) appear more distinct.

Published this week in Science, the study takes the broadest look yet at how genetic variation relates to brain disorders. The results indicate that psychiatric disorders have important similarities at a molecular level, which current diagnostic categories do not reflect.

The study, led by co-senior authors Professor in Psychiatry, Aiden Corvin at Trinity College Dublin and Dr Ben Neale of the Broad Institute of MIT and Harvard, included researchers from more than 600 institutions worldwide. The analysis included all of the genome-wide association (GWAS) data from studies of common brain disorders that the team could identify. The researchers measured the degree of genetic overlap for 25 disorders including 265,218 patients and 784,643 controls. They also studied the relationship between brain disorders and 17 physical and cognitive measures, such as educational attainment, from more than one million individuals.

The brain is a complex organ and difficult to study directly. The classification of brain disorders has evolved over the last century into two main camps, neurological and psychiatric disorders. However, disorders can co-occur in the same person. Until now it hasn’t really been possible to examine the molecular basis of these disorders and their relationships.

The final results indicated widespread genetic overlap across different types of psychiatric disorders, particularly between attention-deficit/hyperactivity disorder(ADHD), bipolar disorder, major depressive disorder, and schizophrenia. The data also indicated strong overlap between anorexia nervosa and obsessive-compulsive disorder (OCD), as well as between OCD and Tourette syndrome.

In contrast, neurological disorders such as Parkinson’s and multiple sclerosis appeared more distinct from one another and from the psychiatric disorders — except for migraine, which was genetically correlated to ADHD, major depressive disorder, and Tourette syndrome.

According to the researchers, the high degree of genetic correlation among the psychiatric disorders suggests that current clinical categories do not accurately reflect the underlying biology.

Commenting on the significance of the research, Trinity Professor Aiden Corvin said:

“In psychiatry we have a tradition of making clear distinctions between disorders based on clinical symptoms. This has been helpful in guiding treatments, but probably isn’t accurate. Our work suggests that mechanisms in the brain can cause overlapping symptoms and this brings us a step closer to understanding how to diagnose and treat these conditions more effectively.”

As a hypothetical example, a single mechanism regulating concentration could drive both inattentive behaviour in ADHD and diminished executive function in schizophrenia. Further exploration of these genetic connections could help define new clinical phenotypes and inform treatment development and selection for patients.

Additionally, within the cognitive measures, the researchers were surprised to note that genetic factors predisposing individuals to certain psychiatric disorders — namely anorexia, autism, bipolar, and OCD — were significantly correlated with factors associated with higher childhood cognitive measures, including more years of education and college attainment. Neurological disorders, however, particularly Alzheimer’s and stroke, were negatively correlated with those same cognitive measures.

“This work is starting to re-shape how we think about disorders of the brain,” says Dr Ben Neale co-lead author at Broad Institute. “If we can uncover the genetic influences and patterns of overlap between different disorders, then we might be able to better understand the root causes of these conditions— and potentially identify specific mechanisms appropriate for tailored treatments.”

In work co-funded by Science Foundation Ireland and the US National Institute of Mental Health (NIMH), Trinity’s Professor Corvin’s team are now undertaking a much deeper examination of the genome as part of international efforts to discover the mechanisms and pathways that underlie these conditions.

The consortia have made their GWAS data accessible online, either freely available for download or by application. They plan to examine additional traits and genetic variants to explore these patterns further, aiming to discover the relevant mechanisms and pathways that underlie and potentially link these disorders.

Funding for this study was provided in part by the National Institutes of Health), the Orion Farmos Research Foundation, and the Fannie and John Hertz Foundation.

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