Polygenic risk score and the psychosis continuum model

Area of Science:

• Psychiatric Genomics
• Neuroscience
• Genetic Epidemiology

Background:

• Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with overlapping clinical features and genetic risk factors.
• These shared genetic underpinnings suggest a potential psychosis continuum, where SZ and BD represent points along a spectrum.

Purpose of the Study:

• To investigate the localization of diagnostic subcategories within the psychosis spectrum using polygenic risk scores (PGRS).
• To determine if SZ and BD PGRS can differentiate between diagnostic groups and subcategories along the psychosis continuum.

Main Methods:

• Assigned SZ and BD PGRS to individuals in an independent sample comprising BD spectrum cases, SZ spectrum cases, and healthy controls.
• Explored potential differences in mean SZ and BD PGRS across various diagnostic spectrums and subcategories.

Main Results:

• Both SZ and BD PGRS were significantly associated with SZ and BD spectrums compared to controls.
• SZ PGRS was linked to SZ, schizoaffective disorder, psychosis not otherwise specified, and BD1; BD PGRS was linked to BD1 and BD2.
• Lifetime psychosis was associated with SZ PGRS, but not BD PGRS, and no significant differences in PGRS were found between diagnostic spectrums or subgroups.

Conclusions:

• Findings provide molecular polygenetic support for the psychosis continuum model.
• The study validates the localization of diagnostic subcategories within this continuum based on polygenic architecture.