Why are Multiple Diagnoses the Norm?

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Why are Multiple Diagnoses the Norm?  

Jim Windell

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

           Is this because mental health clinicians fail to get the diagnosis right the first time? Or do people develop new psychiatric disorders over time?

          Either way, comorbid diagnoses can make treatment challenging and leave patients feeling unlucky and discouraged.

           A new study, just published in the journal Nature Genetics, gives a possible answer as to why comorbidities are the norm – rather than the exception.

           In research for the study, Andrew Grotzinger, an assistant professor in the Department of Psychology and Neuroscience and his colleagues at the University of Texas at Austin and at other collaborating institutions, analyzed publicly available genome-wide association data from hundreds of thousands of people who submitted genetic material to large-scale datasets, such as the UK Biobank and the Psychiatric Genomics Consortium.

           The researchers then looked at genes associated with 11 disorders, including schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, anorexia nervosa, obsessive-compulsive disorder, Tourette syndrome, post-traumatic stress disorder, problematic alcohol use, ADHD and autism. In addition, they looked at data gathered via wearable movement tracking devices, and survey data documenting physical and behavioral traits. Grotzinger and his associates then applied novel statistical genetic methods to identify common patterns across disorders.

           The results?

           Grotzinger and his colleagues found that 70% of the genetic signal associated with schizophrenia is also associated with bipolar disorder. That finding was surprising as, under current diagnostic guidelines, clinicians typically will not diagnose an individual with both. It was also found that anorexia nervosa and obsessive-compulsive disorder have a strong, shared genetic architecture and that people with a genetic predisposition to have a smaller body type or low BMI (body mass index), also tend to have a genetic predisposition to these disorders.

           Not surprisingly, as the two diagnoses often go together, the study found a large genetic overlap between anxiety disorder and major depressive disorder.

           And when analyzing accelerometer data, the researchers found that disorders that tend to cluster together also tend to share genes that influence how and when we move around during the day. For instance, those 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 correlate with genes associated with higher movement throughout the day, and psychotic disorders (schizophrenia and bipolar disorder) tend to genetically correlate with excess movement in the early morning hours. 

           According to Andrew Grotzinger, lead author of the study, “When you think about it, it makes sense.” That is, he notes, depressed individuals often present as fatigued or low energy while those with compulsive disorders can have difficulty sitting still. 

           “Our findings confirm that high comorbidity across some disorders in part reflects overlapping pathways of genetic risk,” said Andrew Grotzinger. He added that the finding 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 coughing disorder, sneezing disorder and aching joints disorder,” Grotzinger said. “This study is a steppingstone toward creating a diagnostic manual that better maps on to what is actually happening biologically.”

           In all, the study identified 152 genetic variants shared across multiple disorders, including those already known to influence certain types of brain cells. For instance, gene variants that influence excitatory and GABAergic brain neurons – which are involved in critical signaling pathways in the brain – appear to strongly underly the genetic signal that is shared across schizophrenia and bipolar disorder.

           While much more needs to be done to determine exactly what the identified genes do, Grotzinger sees the research as a first step toward developing therapies that can address multiple disorders with one treatment. 

           “People are more likely today to be prescribed multiple medications intended to treat multiple diagnoses and in some instances those medicines can have side effects,” he said. “By identifying what is shared across these issues, we can hopefully come up with ways to target them in a different way that doesn’t require four separate pills or four separate psychotherapy interventions.”

           To read the original article, find it with this reference:

Grotzinger, A.D., Mallard, T.T., Akingbuwa, W.A. et al. (2022). Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. Nature Genetics, https://doi.org/10.1038/s41588-022-01057-4

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