Conference Coverage

More data point to potency of genes in development of psychosis

Early findings suggest that positive environment is not protective



ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

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