Multiple diagnoses are the norm with mental illness; new genetic study explains why | CU Boulder today

More than half of people diagnosed with a psychiatric disorder will experience a second or third in their lifetime. About a third have four or more.

This can make treatment difficult and leave patients unlucky and discouraged.

But a sweeping new analysis of 11 major psychiatric disorders offers new insight into why comorbidities are the norm, rather than the exception, in mental illness. The study, published this week in the journal Natural genetics, found that while there is no underlying risk gene or set of genes for each, subsets of disorders including bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; and major depression and anxiety share a common genetic architecture.

“Our results confirm that high comorbidity in some disorders partly reflects overlapping genetic risk pathways,” said lead author Andrew Grotzinger, assistant professor in the Department of Psychology and Neuroscience.

Andrew Grotzinger

The discovery could ultimately open the door to treatments that address multiple psychiatric disorders at once and help reshape the way diagnoses are given, he said.

“If you had a cold, you wouldn’t want to be diagnosed with a cough disorder, a sneezing disorder, and a sore joint disorder,” Grotzinger said. “This study is a stepping stone towards creating a diagnostic manual that better maps what is really going on biologically.”

How the study worked

For the study, Grotzinger and colleagues from the University of Texas at Austin, Vrije Universiteit Amsterdam and other collaborating institutions analyzed publicly available genome-wide association data (GWAS) from hundreds of thousands of people who have submitted genetic material to large-scale datasets, such as the UK Biobank, 23 and Me, IPsych and the Psychiatric Genomics Consortium.

They looked at genes associated with 11 disorders, including: schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder, Tourette’s syndrome, post- trauma, problematic alcohol use, ADHD and autism.

Additionally, they looked at data collected through wearable motion tracking devices and survey data documenting physical and behavioral traits.

Next, they applied new statistical genetic methods to identify common patterns across the disorders.

Related diagnostics

They found that 70% of the genetic signal associated with schizophrenia is also associated with bipolar disorder. This finding was surprising because, according to current diagnostic guidelines, clinicians generally do not diagnose an individual with both.

They also found that anorexia nervosa and obsessive-compulsive disorder have a strong and shared genetic architecture, and that people with a genetic predisposition to have a smaller body type or low BMI (body mass index) have also tend to have a genetic predisposition to these disorders. .

Not surprisingly, as the two diagnoses often go hand in hand, the study found significant genetic overlap between anxiety disorder and major depressive disorder.

When analyzing the accelerometer data, the researchers found that disorders that tend to cluster also tend to share genes that influence how and when we move during the day.

For example, people with internalizing disorders, such as anxiety and depression, tend to have a genetic architecture associated with low movement throughout the day. Compulsive disorders (OCD, anorexia) tend to be correlated with genes associated with greater movement throughout the day, and psychotic disorders (schizophrenia and bipolar disorder) tend to be genetically correlated with excessive movement during the day. early morning.

“When you think about it, it makes sense,” Grotzinger said, noting that people who are depressed often present as tired or low-energy, while those with compulsive disorders may have difficulty staying still.

In total, the study identifies 152 genetic variants shared by several disorders, including those already known to influence certain types of brain cells.

For example, genetic variants that influence brain excitatory and GABAergic neurons – which are involved in critical signaling pathways in the brain – appear to strongly underlie the genetic signal shared by schizophrenia and bipolar disorder.

And after

Although much work remains to be done to determine exactly what the identified genes do, Grotzinger sees the research as a first step toward developing therapies that can treat multiple disorders with a single treatment.

“People are more likely today to be prescribed multiple medications to treat multiple diagnoses, and in some cases these medications can have side effects,” he said. “By identifying what these issues share, we can hopefully find ways to target them in a different way that doesn’t require four separate pills or four separate psychotherapy interventions.”

In the meantime, simply understanding the genetics underlying their disorders may reassure some.

“It’s important for people to know that they haven’t just had a terrible roll of the dice in life, that they’re not dealing with several different issues, but rather a set of risk factors that are overwhelming them. all.”

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