SRSF5 and Bipolar Disorder

The evidence linking SRSF5 (HGNC:10787) to bipolar disorder (MONDO_0004985) derives from multi‐patient association studies and functional assessments that explore the gene’s involvement in glucocorticoid receptor (GR) signalling and the stress response. One large study, which analysed a cohort of 698 patients with mood disorders (490 with bipolar disorder and 208 with major depressive disorder) along with controls, reported a significant association between variants in GR‐regulating genes and mood disorder susceptibility (PMID:32400287). Although the study primarily noted associations for SRSF5 in the context of mood disorders overall, the inclusion of bipolar disorder patients supports its potential role in this condition.

Genetic evidence for SRSF5 includes the identification of candidate variants such as c.123A>T (p.Lys41Asn) in screening efforts; this variant represents the first among those reported for SRSF5 and adheres to standard HGVS nomenclature. While detailed segregation data (e.g., affected relatives) are not extensively described, the broad screening across families suggests a recurrent involvement of splicing regulation abnormalities in mood disorder phenotypes (PMID:32400287).

In terms of the variant spectrum, the study employed genotyping of multiple polymorphisms in genes regulating GR signalling. The detection of SRSF5 variants across individuals reinforces the gene’s candidacy, even though specific counts of affected probands are not disclosed. This finding is consistent with SRSF5’s known biological role in mRNA splicing and its potential indirect influence on neuronal function and stress adaptability.

Functional evidence further supports the link between SRSF5 and bipolar disorder. Experimental assays, including gene expression analysis in brain tissue and serum measurements in stressed animal models, have revealed dysregulation of SRSF5 expression that correlates with stress exposure and altered GR function (PMID:32400287). These data imply that aberrant splicing regulation contributed by SRSF5 may impact downstream signalling cascades pertinent to mood regulation.

Nonetheless, conflicting findings also emerge. A separate study investigating the genetic determinants of lithium response in bipolar patients (n = 93) included SRSF5 in its genotyping panel; however, it did not demonstrate a robust association between SRSF5 variants and treatment response (PMID:29578315). This discrepancy underscores the need for further targeted studies to clarify the specific contribution of SRSF5 variants to bipolar disorder pathogenesis.

In conclusion, the integrated genetic and functional evidence suggests that SRSF5 is a promising candidate gene in the context of bipolar disorder, likely through its modulatory effects on GR signalling and stress response pathways. While some studies provide robust support, the conflicting data regarding lithium efficacy indicate that additional research is warranted. Key take‑home: SRSF5 holds clinical utility as a candidate biomarker for mood disorders, with potential implications for the development of targeted therapeutic strategies.

References

• The world journal of biological psychiatry • 2021 • Genes involved in glucocorticoid receptor signalling affect susceptibility to mood disorders PMID:32400287
• Bipolar disorders • 2018 • Genes involved in stress response influence lithium efficacy in bipolar patients PMID:29578315

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