Genetic Study Separates Schizophrenia and Bipolar Disorder Pathways
Genetic modeling separates schizophrenia-specific risk from shared psychosis genes linked to cognition.
Distinguishing between bipolar disorder and schizophrenia is often difficult since the two conditions share many biological traits.
A team at King’s College London identified separate genetic pathways for each, finding that markers unique to schizophrenia drive cognitive decline while shared markers link to better education.
The genetic paradox of schizophrenia and bipolar disorder
Psychiatrists often see a puzzling mix of symptoms in patients that blur the lines between schizophrenia and bipolar disorder. While both conditions involve psychosis, patients with bipolar disorder often retain higher cognitive skills. In contrast, those with schizophrenia frequently experience significant challenges with memory and processing speed.
This difference has created a long-standing riddle in psychiatric genetics.
“We know that schizophrenia and bipolar disorder share a considerable genetic overlap and that many people with these conditions can present with similar symptoms. People with schizophrenia, however, typically have more cognitive difficulties than those with bipolar disorder,” said first author Dr. Cameron Watson, an academic clinical fellow from King’s College London.
Previous data have found that genetic markers for schizophrenia are linked to lower IQ scores, yet simultaneously, these same markers appeared to link to higher educational achievement. Researchers struggled to explain how a single disorder could show such opposing effects, raising questions about the true nature of the genetic risk involved.
Most earlier studies treated schizophrenia as a separate, isolated entity, and they ignored how the shared genetic foundations of bipolar disorder might influence these outcomes.
A team from King’s College London used modeling to separate these genetic paths to isolate the specific risks of schizophrenia from the traits it shares with bipolar disorder.
Genomic modeling of schizophrenia and bipolar disorder risk
The team analyzed data from the Psychiatric Genomics Consortium, comparing the genetic profiles of 67,390 people with schizophrenia and 41,917 with bipolar disorder. They used a method called Genomic structural equation modeling, which allowed them to identify two distinct paths: a shared psychosis risk and a risk specific to schizophrenia.
Genomic structural equation modeling
Genomic structural equation modeling is a statistical tool used to analyze genetic relationships among traits or disorders. It allows researchers to separate genetic markers that overlap between conditions from those that belong to just one.
The analysis identified 63 genetic variants unique to schizophrenia and 78 variants shared with bipolar disorder.
“Our study has harnessed the latest advances in genetics to shed some light on the biological drivers of these differences,” said Watson.
The results showed a clear difference in how these genes affect the brain. The variants unique to schizophrenia showed a strong negative correlation with IQ and educational attainment, hindering cognitive development.
However, the variants shared with bipolar disorder told a different story. These shared markers correlated with higher educational attainment and had a smaller negative effect on IQ.
The team confirmed these patterns using individual-level data from 380,000 participants in the UK Biobank.
Clinical implications for treating schizophrenia and bipolar disorder
Splitting the diagnosis helps explain why two patients with the same label can have different lives. One person might struggle with daily tasks, while another achieves academic honors.
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The study suggests we need diagnostic criteria that reflect this biological reality rather than clinical symptoms alone.
“These findings highlight that the genetics of schizophrenia are more complex than we once thought. Two people with the same diagnosis can have very different cognitive and educational outcomes,” said senior author Dr. Evangelos Vassos, a clinical reader from King’s College London.
“We already know that the environment influences these differences, but our study provides evidence for the relevance of distinct genetic signatures. Current diagnostic criteria can obscure distinct biological pathways; understanding them could eventually help us refine how we diagnose and treat psychotic disorders,” added Vassos.
These distinct pathways could lead to targeted treatments, where genetic signatures are used to choose medications or cognitive therapies. Instead of a one-size-fits-all approach, treatment could target the specific biological drivers of each patient's condition.
While environmental factors remain important, these genetic signatures provide a clear map for future research and personalized care.
Reference: Watson CJ, Zvrskovec J, Merola GP, et al. Splitting schizophrenia: divergent cognitive and educational outcomes revealed by genomic structural equation modelling. Mol Psychiatry. 2026. doi: 10.1038/s41380-026-03444-3
This article is a rework of a press release issued by King’s College London. Material has been edited for length and content.
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