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Negative symptoms, anxiety common in youth with higher genetic risk for schizophrenia

Schizophrenia polygenic risk scores indicated broad negative symptoms but not isolated psychotic symptoms, according to recent findings.

“Genetic advances now provide the opportunity to extend the power and generalizability of high-risk studies into the general population by examining individuals according to genetic risk. Although individual loci have small effects on risk, multiple-loci approaches show that, cumulatively, alleles on current [genome-wide association study] platforms explain one-half to one-third of the genetic risk for schizophrenia,” Hannah J. Jones, PhD, of University of Bristol, England, and colleagues wrote.

To assess associations between genetic risk for schizophrenia and different phenotypes during adolescence, researchers analyzed data from the Avon Longitudinal Study of Parents and Children. Logistic regression was used to assess associations between schizophrenia polygenic risk scores and psychotic experiences, measured by the Psychosis-Like Symptom

Interview at age 12 years and 18 years; negative symptoms, measured by Community Assessment of Psychic Experiences at age 16.5 years; depressive disorder, measured by Development and

Well-Being Assessment at age 15.5 years; and anxiety disorder, measured by Development and

Well-Being Assessment at age 15.5 years. Overall, 3,676 to 5,444 participants completed assessments from age 12 to 18 years.

Polygenic risk scores created using single-nucleotide polymorphisms with a training set P ≤ .05 threshold were associated with negative symptoms (OR per standard deviation increase in polygenic risk score = 1.21; 95% CI, 1.08-1.36) and anxiety disorders (OR = 1.17; 95% CI, 1.06-1.29).

Researchers found no evidence of an association between schizophrenia polygenic risk scores and psychotic experiences or depressive disorder.

Results were “mostly consistent” across different training-set P value thresholds and different cutoffs and measures of psychopathological outcomes, according to researchers.

“In summary, Jones et al have clarified the phenotypic effects of the genetic predisposition toward schizophrenia in adolescence. Most interestingly and consistent with several lines of prior evidence, the schizophrenia [polygenic risk score] predisposes toward a rather broad set of negative symptoms but not isolated psychotic symptoms. Some aspect of anxiety syndromes is also likely part of their phenotypic spectrum but not depression,” Kenneth S. Kendler, MD, of Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, wrote in an accompanying editorial. “We will surely see more studies using the [polygenic risk score] as a potentially powerful tool to clarify the phenotypic spectrum and/or developmental precursors of our major psychiatric disorders. This study represents a promissory note of more to come.” – by Amanda Oldt

Disclosure: Jones and Kendler report no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.