100-year-old brains may help treat mentally ill

INDIANA U. (US) — Using a simple blood test, DNA from brains preserved more than a century ago may help improve diagnosis and treatment for people with psychological illnesses.

The brain samples under investigation come from turn-of-the-century patients who suffered from mental disorders at Central State Hospital, an asylum established in the mid-1800s for the state of Indiana’s mentally ill that now houses the Indiana Medical History Museum.

John Pless, professor emeritus of pathology at Indiana University and a former chair of the museum board of trustees, first proposed the brains might be able to help advance modern medicine.

George Sandusky, senior research professor of pathology and laboratory science at IU, who also serves on the museum board, was originally trying to simply determine whether the aging specimens contained viable genetic information.

“This work could make an impact on patient care — a huge impact,” says Sandusky. “It’s going to help diagnose patients with mental disorders quicker and faster.”

Using brain donors from traditional sources only brings in about 12 new subjects per year, he says. The museum collection, which includes over 400 specimens, could speed by decades the arrival of new diagnoses and treatments for those suffering from bipolar disorder, schizophrenia, and post-traumatic stress disorder.

The key breakthrough in the project arrived last summer after Sandusky and two undergraduate student researchers, Erin Niland and Audrey McGuire, discovered that functional DNA could be isolated and extracted from the museum’s brain samples, despite their extreme age and the preservation techniques used by 19th-century doctors.

“They preserved the brains with the best science of their time,” Sandusky says. “The preservation techniques from the era were almost as good as ours from the 1970s, 1980s, 1990s, and 2000s. I was shocked by the quality.”

Earlier tests conducted in 2010 yielded unusable results, but new technology—as well as experienced lab workers and cutting-edge test methods—ultimately “cracked the code.”

The results support work by Alexander Niculescu, associate professor of psychiatry who is seeking to advance personalized medicine in the treatment of mental illness using biomarkers for bipolar disorder, schizophrenia, and PTSD.

Biomarkers—a specific region on a gene that suggests susceptibility to a certain illness—are an increasingly common tool in the fight against cancer and other diseases, but no reliable test exists for psychiatric disorders.

Niculescu, however, is making significant advances in pinpointing potential biomarkers for mental illness through research conducted at the Richard L. Roudebush VA Medical Center in Indianapolis. The samples from the Indiana Medical History Museum are being tested for the same telltale signs.

The goal is to use data from both studies to assist future physicians in creating a personal genetic profile for people suffering from psychiatric illnesses to ensure they are diagnosed quickly and accurately.

The search for identifiable biomarkers will pioneer new, innovative treatments in clinical practice by eliminating the current system of diagnosis, which requires significant trial and error.

“If you come in with a psychiatric illness today, you can’t really separate different mental disorders,” Sandusky says. “You have to try several drugs before finding one that even works—and that may take months.”

All tissues used in the research received ethical and legal approval from an internal review board at the state and at the university.

The research was supported by the National Cancer Institute Cancer’s Genome Atlas Program and National Institutes of Health Director’s New Innovator Award.

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