DNA lesions and repair-gene expression differ in bipolar disorder and sibling groups

People with bipolar disorder and their unaffected siblings had significantly higher concentrations of oxidative DNA lesions than healthy controls in a comparison of 127 participants, alongside differences in the expression of genes associated with nucleotide excision repair. The study found elevated urinary levels of 8,5′-cyclopurine-2′-deoxynucleosides, or cPUs, in both the bipolar disorder group and the sibling group, while the repair-related gene-expression patterns were not identical across the three groups. Researchers assessed 44 individuals with bipolar disorder, 37 unaffected siblings and 46 healthy controls.

Urinary cPU concentrations were quantified with liquid chromatography–tandem mass spectrometry, while expression of six nucleotide excision repair genes—XPB, XPC, XPD, XPF, ERCC1 and CSB—was measured in peripheral blood samples using quantitative reverse transcription PCR. The investigators described the study as an assessment of DNA-lesion levels and repair-gene expression in people with bipolar disorder, their unaffected siblings and healthy controls. The cPUs examined are tandem oxidative lesions that distort the DNA helix and impair replication and transcription.

The source study states that they are repaired primarily by the nucleotide excision repair pathway. Both the bipolar disorder and sibling groups had significantly elevated urinary cPU concentrations compared with healthy controls. R-cdA concentrations were highest in the sibling group.

These observations show that elevated lesion concentrations were present in the two groups sharing a family connection, rather than only among participants diagnosed with bipolar disorder. The group comparison did not establish whether the concentrations preceded illness, caused bipolar disorder or predicted future symptoms. Expression of four repair-related genes was increased in the sibling group: XPB, XPF, ERCC1 and CSB.

XPC expression was elevated in both the bipolar disorder and sibling groups relative to healthy controls. Other comparisons distinguished the sibling group from the bipolar disorder group. XPB, XPF and CSB expression was significantly higher in siblings than in participants with bipolar disorder, whereas XPD expression was increased in the bipolar disorder group compared with both the sibling and healthy-control groups.

The results therefore comprised elevated cPU concentrations in both family-linked groups and distinct patterns of repair-gene expression among bipolar disorder participants, unaffected siblings and controls. The authors interpreted the combined findings as support for prior evidence implicating oxidative DNA damage and repair mechanisms in bipolar disorder pathogenesis. They proposed that the cPU lesions and the differing expression patterns may be useful as additional molecular markers and may indicate a potential familial vulnerability associated with the development of bipolar disorder.

The study itself does not demonstrate that elevated lesions or altered gene expression cause the disorder, that either precedes its onset, or that either constitutes a clinical diagnostic test. The results instead identify measurable molecular differences in bipolar disorder and unaffected sibling groups that warrant further investigation as potential indicators of oxidative DNA damage and altered repair activity.

Subject of Research: Oxidative DNA lesions and nucleotide excision repair gene expression in bipolar disorder, unaffected siblings and healthy controls

Article Title: Cyclopurine DNA lesions and repair in individuals with bipolar disorder and their unaffected siblings

Article References: Arat Çelik, H. E., Tuna, G., Akşahin, İ. C., Yılmaz, S., Fettahoğlu, İ., Eslami Abriz, A., Gör, C., Çörekli, E., Kök Kendirlioğlu, B., Dal Bekar, N. E., Çelik, Ö. F., Yorguner, N., & Ceylan, D. (2026). Cyclopurine DNA lesions and repair in individuals with bipolar disorder and their unaffected siblings. Translational Psychiatry. https://doi.org/10.1038/s41398-026-04519-z

Image Credits: AI Generated

DOI: 10.1038/s41398-026-04519-z

Keywords: bipolar disorder, oxidative DNA lesions, nucleotide excision repair, DNA repair, familial vulnerability, gene expression, R-cdA, mass spectrometry, peripheral blood, biomarkers, Cyclopurine, lesions