A new research study has revealed that genetic variants associated with risk for schizophrenia and other psychotic disorders are also associated with performance on measures of IQ, memory and social cognition. The discovery was made by the National University of Ireland, Galway Professor of Psychology Gary Donohue, in association with colleagues from Trinity College, Dublin.  The study results have just been published in leading journal, JAMA psychiatry.  This suggests that early screening for schizophrenia risk may in the future be done via tests on standard measures already used today.

Professor Gary Donohoe said: “These findings support the view that the genetics of schizophrenia and cognition overlap. The findings also raise the possibility that the risk of developing schizophrenia may be identified by changes in cognitive ability; tell-tale signs found in IQ, memory or social intelligence tests. These cognitive deficits often appear before the emergence of clinical symptoms and go on to predict individual levels of disability. Understanding how genetic variants contribute to this aspect of disability, both individually and interaction, is an important step towards understanding the underlying biology and developing better and more personalized treatments.”

Schizophrenia or bipolar disorder affects about one in 50 adults. Treatments are available, but the successful treatment rates vary. Disability in these disorders is significantly affected by difficulties with a wide range of neuropsychological problems, including general cognitive ability, memory function, and cognitive abilities relevant to engaging and dealing with others.

Co-first author Dr. Hargreaves said ‘what is perhaps most novel about the study is the move from focusing on single genetic variants to considering the effects of multiple, related risk variants at the same time. The fact that we were able to account for a greater proportion of the variance in cognitive performance by looking at multiple variants, suggests that this approach represents an important next step in modeling the genetic complexity of cognition and identifying risk factors for psychosis’.

The study assessed performance on a number of cognitive functions known to be affected in psychosis. A total of 424 patients participated in the study, including 340 with schizophrenia or schizoaffective disorder, and 83 with bipolar or major depressive disorder with psychotic features. Patients were given individual scores based on their loading for genetic variants interacting with ZNF804A, the first genome wide significant variant to be identified for schizophrenia.

Across patient groups, higher scores on this ZNF804A interaction pathway were associated with poorer performance on multiple cognitive measures, including both general cognitive ability and a measure social cognition, often popularly referred to as social intelligence.

Research Paper Details: Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway