This article is more than 5 years old. Information may no longer be current.

Study shows genetic risk gradient across schizophrenia, bipolar disorder

Recent findings indicated a polygenic risk gradient across schizophrenia and bipolar disorder, which was associated with the presence and severity of mood-incongruent psychotic symptoms.

“Mood-incongruent psychotic features are associated with poor prognosis and poor lithium response and are qualitatively similar to the prototypic symptoms of [schizophrenia], suggesting that [bipolar disorder] with psychosis and particularly mood-incongruent psychotic features may specify a subgroup or stratum with stronger etiological links to [schizophrenia],” Judith Allardyce, MRCPsych, PhD, of Cardiff University, Wales, and colleagues wrote. “Stratified linkage and candidate-gene studies of [bipolar disorder] associations with chromosomal regions and genes implicated in [schizophrenia]show stronger effects in psychosis and mood-incongruent subsamples, providing some support for this causal heterogeneity hypothesis; however, lack of consistency in earlier linkage and candidate-gene studies renders the overall support weak.”

To determine associations between common-variant liability for schizophrenia, shown by polygenic risk scores, and psychotic presentations of bipolar disorder, researchers conducted a case-control study in the United Kingdom. The study cohort included 4,436 individuals with bipolar disorder; 4,976 individuals with schizophrenia and 9,012 controls. Mean age at interview was 46 years.

Researchers observed an exposure-response gradient across clinical phenotypes, with the strongest polygenic risk scores association for schizophrenia risk (RR = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective bipolar disorder (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.3; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11).

There was an effect gradient, indexed by the nature of psychosis, among participants with bipolar disorder.

Significant mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and bipolar disorder with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15).

“These results highlight the usefulness of genetic data to dissect clinical heterogeneity within and across disorders and suggest further research could potentially aid in defining patient stratifiers with improved biological precision and validity, moving us tentatively toward precision medicine in psychiatry,” the researchers concluded. – by Amanda Oldt

Disclosures: Allardyce reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.