Abstract
Suicide is a major public health problem with ∼1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT2CR) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT2CR mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT2CR, that is, VSV (Val156–Ser158–Val160). Because the VSV isoform of 5-HT2CR exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.
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Acknowledgements
Postmortem brain tissue was donated by The Stanley Medical Research Institute's array collection courtesy of Drs Michael B Knable, E Fuller Torrey, Maree J Webster and Robert H Yolken. This study was supported by VA Merit award to SD and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC) (LJS, VH and SD). We thank Dr William M Byne for his help in the preparation of the article.
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Dracheva, S., Patel, N., Woo, D. et al. Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide. Mol Psychiatry 13, 1001–1010 (2008). https://doi.org/10.1038/sj.mp.4002081
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DOI: https://doi.org/10.1038/sj.mp.4002081
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