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A deep understanding of the neural basis of cognitive impairment in schizophrenia is critical for the development of treatments for this disorder, as cognitive dysfunction can predict clinical outcomes such a relapse frequency and everyday functioning. Achieving this level of understanding is possible by studying post-mortem human brain tissue. However, thus far, scientists have been prevented from doing so due to significant challenges related to the absence of information on the cognitive aptitude of postmortem subjects.

Researchers including Drs. Jill Glausier, Mary Ann Kelly, and David Lewis from the University of Pittsburgh conducted a study to address these challenges and thus expand the potential for scientists to use postmortem brain tissue to understand the neural foundation of cognitive impairment.

The team assembled a cohort of 507 postmortem human subjects who met criteria for schizophrenia, major depressive disorder or bipolar disorder and an unaffected comparison group. They gathered information on the levels of educational and occupational attainment—useful proxy measures of cognitive aptitude—for the proband subjects and their parents.

This information was gathered through an investigative procedure known as psychological autopsy, which entails a structured interview with the next-of-kin and/or another close friend or family member regarding demographic, psychiatric and medical treatments for the subject, as well as for family members. Additional information was obtained through treatment records, social media and educational and legal documents. In addition to carefully documenting demographic, psychosocial, and family information, an integral part of the psychological autopsy is diagnostic confirmation. By using standardized interview techniques, the team was able to systematically incorporate the informant’s report along with information found in the subject’s treatment records. Dr. Kelly commented, “The psychological autopsy provides value in terms of the breadth of demographic and psychosocial information gathered along with the rigor of a standardized method to increase diagnostic accuracy.”

In a study recently published in Psychological Medicine, the research team reported that both educational and occupational attainment was lowest in subjects with schizophrenia and highest in subjects with bipolar disorder and the unaffected comparison group. Additionally, in contrast to the general population, educational and occupational attainment in the subjects with schizophrenia was not higher relative to their parents.

“The absence of measures of premortem cognitive aptitude in postmortem subjects has presented a major challenge to interpreting the relationship between the severity of neural alterations and cognitive deficits within the same subjects,” Dr. Glausier said. “These findings demonstrate that readily available data, information regarding educational and occupational attainment, are sensitive proxy measures of the severity of cognitive impairments individuals experienced during life. This finding provides a much-needed piece of the puzzle so that we can robustly interrogate the neural substrates of cognitive dysfunction in schizophrenia.”

Proxy measures of premortem cognitive aptitude in postmortem subjects with schizophrenia
Glausier JR, Kelly MA, Salem S, Chen K, Lewis DA
Psychological Medicine 1-8. DOI: https://doi.org/10.1017/S0033291719000382