Objective:

To identify genetically predicted associations between urinary metabolites and psychiatric disorders as potential biomarkers for differential diagnosis, with implications for clinical practice.

Key Findings:

• No significant associations for autism spectrum condition, major depressive disorder, or Tourette syndrome.
• 21 associations were exclusive to single disorders: 5 with schizophrenia, 15 with bipolar disorder, and 1 with ADHD, highlighting the potential for misdiagnosis.
• Inverse association between urinary tyrosine levels and schizophrenia risk was the most robust finding.
• Overlap in metabolite associations between bipolar disorder and schizophrenia, with 22 shared analytes, suggesting clinical relevance.

Interpretation:

The findings suggest potential urinary biomarkers for psychiatric disorders, particularly schizophrenia and bipolar disorder, but require further validation.

Limitations:

• Findings should not be interpreted as clinically validated biomarkers.
• Urinary analyte levels may vary with hydration, diet, and activity.
• Limited ability to perform extensive sensitivity analyses due to reliance on single-nucleotide polymorphism instruments.
• Statistical power limitations for some psychiatric disorder datasets, potentially affecting findings for major depressive disorder, autism spectrum condition, and Tourette syndrome.
• Overlap in metabolite associations may lead to misdiagnosis in real-world patient populations.

Conclusion:

Further validation is needed before clinical application, including targeted metabolomics studies and replication across diverse populations to ensure generalizability.