Associations of cytokine gene polymorphisms with post-stroke depression

Abstract

Objectives. Inflammatory cytokines are implicated in the pathophysiology of both stroke and depression, and their production is influenced by the transcriptional activity of particular gene polymorphisms. We hypothesised that alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would be associated with post-stroke depression (PSD). Methods. In 276 stroke cases, depression was diagnosed using DSM-IV, and classified into major PSD (N = 29), all (major plus minor) PSD (N = 77), and control (N = 199) groups. Genotyping for six pro-inflammatory polymorphisms (TNF-α –850C/T and –308G/A, IL-1β –511C/T and + 3953C/T, IL-6 –174G/C, and IL-8 –251T/A) and two anti-inflammatory polymorphisms (IL-4 + 33T/C and IL-10 –1082G/A) was conducted. Individual associations with PSD were estimated using logistic regression models. Total numbers of potential risk alleles were calculated for pro-inflammatory and anti-inflammatory cytokine genes and analysed against depression using χ²-tests. Results. The IL-4 + 33C/C genotype was associated with major PSD, and the IL-10 –1082A/A genotype was associated with all PSD. Increasing numbers of risk alleles for these two anti-inflammatory cytokine genotypes were significantly associated with both PSD categories. No significant associations were found with any pro-inflammatory cytokine allele. Conclusions. Alleles associated with reduced anti-inflammatory cytokine function were associated with PSD, supporting the cytokine hypothesis in its etiology.

Key words::

• Depression
• cytokines
• genetics
• stroke
• interleukins

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0087344). Dr. Robert Stewart is funded by the NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London.

Statement of Interest

None to declare.

Additional material

Full references for Table I are available online.