Polygenic scores can help determine schizophrenia subgroups

Schizophrenia subgroups with distinct cognitive development trajectories can be determined using adult cognitive data, according to study findings published in American Journal of Psychiatry. Researchers noted that these subgroups have significantly different profiles of cognitive, academic and psychiatric genetic influence.

“Three developmental trajectory subtypes are frequently described: one including those with a lifelong history of impaired social, behavioral and/or intellectual functioning and an insidious progression toward psychotic illness; a second including individuals with a benign developmental course through adolescence followed by a relatively abrupt onset of psychotic symptoms; and a third including individuals who experience a prominent prodromal phase that begins and progresses during adolescence before transitioning into psychosis,” Dwight Dickinson, PhD, JD, of the Clinical & Translational Neuroscience Branch of the NIMH, and colleagues wrote. “These distinctions have been linked to important course, symptom and outcome variables.”

Dickinson and colleagues analyzed demographic, clinical and genetic data from the NIMH for 540 patients with schizophrenia, 247 unaffected siblings and 844 controls. They derived cognitive trajectory subgroups through cluster analysis using estimates of current and premorbid IQ, and they used standard methods to generate polygenic scores. They tested associations using logistic regression and general linear models.

The researchers reported that among the schizophrenia group, cluster analyses identified three cognitive trajectory subgroups — preadolescent cognitive impairment (19%), adolescent disruption of cognitive development (44%) and cognitively stable adolescent development (37%). Profiles of the four polygenic scores that separately summarized the influence of common genetic variants associated with ADHD, educational attainment, general cognition and schizophrenia significantly predicted 7.9% of the variance in subgroup membership.

Dickinson and colleagues noted that subgroup characteristics converged with genetic patterns. The best adult clinical outcomes occurred among cognitively stable individuals, who differed from controls only in schizophrenia polygenic scores. Individuals with adolescent disruption of cognitive development had the most severe symptoms after diagnosis and experienced cognitive impairment. This subgroup had the highest schizophrenia polygenic scores and disadvantageous cognitive polygenic scores compared with control subjects and cognitively stable individuals. Individuals who exhibited preadolescent impairment in academic and cognitive performance and poor adult outcome had a generalized polygenic score disadvantage compared with control subjects. They were the only subgroup to differ significantly in ADHD and education polygenic scores, the researchers noted.

“The use of current methods for creating [polygenic scores] also involves certain limitations,” they wrote. “Although it is clear that psychiatric disorders involve both common and rare forms of genetic variation, [polygenic scores] reflect only common genetic variants, missing important elements of the genetic landscape.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.