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The following is a summary of “Association of neurotransmitter pathway polygenic risk with specific symptom profiles in psychosis,” published in the March 2024 issue of Psychiatry by Warren et al.
To understand psychiatry is to understand the pathways linking genetic risk to psychiatric symptoms.
Researchers conducted a prospective study to test the correlation between diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis.
They included 205 demographically diverse cases with a psychotic disorder along with 115 matched controls and calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS data. Pathway PGSs (pPGSs) for SZ risk affecting glutamate, GABA, dopamine, and serotonin pathways were also calculated. Associations between genetic risk and diagnosis, symptoms, and endophenotypes were examined.
The results showed psychosis subjects with elevated SZ PGS compared to that of controls, along with a higher risk of SZ or BP on diagnoses. Neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes. Glutamate was associated with SZ diagnosis and cognitive control, while dopamine was associated with global functioning. Clustering identified three diagnostically mixed case groups, showing substantial genome-wide risk, with specific risk in glutamatergic and GABAergic pathways observed in one group.
Investigators concluded that pathway-based PGS analysis could be valuable for studying genetic mechanisms underlying psychiatric endophenotypes. However, further population and mechanism-level research is needed to validate these findings.
Source: nature.com/articles/s41380-024-02457-0
