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Sunday, September 26, 2021

Not just a disease of the mind

Ole Andreassen, a professor at the UC San Diego School of Medicine, published an article on Feb. 7 in The American Journal of Human Genetics in which he definitively connected high rates of cardiovascular disease (CVD) with schizophrenia.

The news of the connection between these diseases is not new; it is a well-established fact that schizophrenic patients are two times more likely to develop cardiovascular disease than the general population — a correlation known as having high comorbidity. However, Andreassen helped pioneer a new technique in genetic analysis showing that several of the mutated genes active in one disease are also present in the other.

“I hope to change the way we view psychiatric disorders and make people realize that they are system disorders, affecting the whole body,” Andreassen said. “Unfortunately, that requires better understanding of the underlying mechanisms of the disorder … We have to realize that there is a high number of underlying genetic factors — not one schizophrenia gene.”

The primary research method Andreassen utilized involved genome-wide association studies (GWAS) in order to observe single nucleotide polymorphisms (SNPs). Researchers compared the genomes of subjects in a “healthy” control group with the genomes of patients suffering from CVD and separate patients with schizophrenia. There was an additional subgroup of patients with both CVD and schizophrenia.

Genomes are constructed of four components called nucleotides (A, T, C and G), which are arranged in specific orders that determine function.

“SNPs are small changes in the genome sequence, such that some people have the genotype AT, while others are TT, and others are AA,” said Chuck Langley, a professor of genetics at UC Davis.

Andreassen’s study looked at the SNPs of the research subjects and correlated regions of their genetic codes that were likely to harbor a mutated gene.

“The innovative aspect is the development of new statistical tools and applying them to the huge GWAS available, which is a true “genetic epidemiology,” Andreassen said.

His new method utilized these statistical tools in order to quantify the high level of comorbidity between CDV and schizophrenia, making it possible to identify locations of mutations that are common to both diseases.

A gene that affects multiple traits is known as a pleiotropic gene. Andreassen was able to identify 10 possible pleiotropic genes highly associated with schizophrenia and CVD. The same genes that are thought to cause schizophrenia are also responsible for affecting blood pressure, cholesterol, triglycerides, type 2 diabetes, body mass index (BMI) and waist-to-hip ratio (WHR).

However, though some of the same genes implicated in schizophrenia may be responsible for contributing to CVD, their presence alone does not necessarily account for the high rates of the CVD within schizophrenic patients. One possible explanation lies in the constant interplay between genes and external environment.

“The significantly higher rate of smoking among mental health consumers and the side effects of antipsychotic medications cannot be ignored as possible factors,” said Alyssa Parsons, a mental health worker at the Yolo Community Care Continuum. “What’s interesting about this situation is that nicotine does have beneficial effects on psychiatric conditions. For example, it reduces anxiety and irritability.”

However, a plethora of research has proven the multitude of detrimental health effects caused by smoking, not the least of which is CVD.

Furthermore, according to Parsons, a pretty big portion of the antipsychotics prescribed by psychiatrists cause massive weight gain, as well as a slew of other health problems. Plenty of research has also gone into connecting obesity with CVD.

Andreassen’s article proves that the factors connecting schizophrenia and CVD are genetically heritable; however, it is impossible to extricate this genetic heritability from the environmental factors common to most schizophrenic patients.

KYLE SCROGGINS can be reached at science@theaggie.org.

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