Summary: Study finds few differences in the profiles of genes that influence cognition between those with severe mental health disorders and the general population.
Source: University of Miami
A study funded by the Veterans Administration and directed by researchers at the University of Miami Miller School of Medicine has shown few differences in the profiles of genes that influence cognition between people with schizophrenia, bipolar disorder and the general population. This surprising finding could provide new insights into therapies designed to improve cognition. The study was published in the American Journal of Medical Genetics.
“For years, people have been talking about cognition in schizophrenia and bipolar disorder and how cognitive impairments in these apparently distinct conditions are likely qualitatively different from each other, as well as qualitatively different from what’s going on in the general population,” said lead author Philip D. Harvey, Ph.D., professor of psychiatry and behavioral sciences. “What we find here is that the biggest signal is normal. The genomics of cognition in the general population appears to be driving all these other findings.”
The study assessed more than 9,000 veterans with schizophrenia and bipolar disorder. In addition to analyzing genomic data, the research team went much deeper than previous efforts, confirming participants’ diagnoses and giving them cognitive tests. This is the largest study in mental health conditions to combine genome-wide association methods with cognitive assessments.
“Our study is small by comparison – some of the previous studies had 1.2 million people in them,” said Dr. Harvey. “But it is completely different in that we personally saw every research participant. The others are all essentially database studies.”
In addition, by validating the genomics with actual cognitive testing, the VA/Miller School team has added new context to these large database projects, giving researchers robust cognitive data to better analyze the results from multiple studies with different methods.
Learning that the genomics of cognition for schizophrenia, bipolar disorder and the general population have substantial overlap also provides new clues to improve therapies.
“If you know what the genomics are, you can start considering gene therapies,” said Dr. Harvey. “You can also start understanding whether cognitive impairments in schizophrenia and bipolar disorder are essentially an exaggerated case of normal variation.”
This could have an almost immediate impact on patients with severe mental illness. Because the structure and genetic determinants for cognition vary so little between the different illnesses, as well as the general population, assessment and intervention strategies that are proven in schizophrenia may be applicable to people with bipolar disorder and vice versa.
“You may not need specialized assessments for cognition in schizophrenia or bipolar disorder, and you may not need different treatments either,” said Dr. Harvey. “We should be pursuing treatment options for people with schizophrenia and bipolar disorder to treat cognitive impairment that are not necessarily different from each other. And we should be doing assessments that differ only in their level of difficulty, not qualitatively different assessments.”
Genome‐wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder
Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome‐wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome‐wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition‐related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.