Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide
Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide
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DOI：
10.1038/sj.mp.4002081
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发表时间：
2008-11-01
影响因子：
11
通讯作者：
Haroutunian, V.
中科院分区：
文献类型：
--
作者：
Dracheva, S.;Patel, N.;Haroutunian, V.
自杀是一个重大的公共卫生问题，全世界每年约有100万人自杀。高达90%的自杀成年人至少有一种精神病诊断，如重度抑郁症，双相情感障碍（BPD），精神分裂症（SZ），药物滥用或依赖。一个尚未得到解答的问题是，自杀的生物学基础是否与发生自杀的精神疾病的生物学基础不同。5-羟色胺2C受体（5-HT 2CR）与抑郁症和自杀有关。因此，我们比较了自杀或死于其他原因的受试者死后前额叶皮层标本中其mRNA编辑变体的频率。所有自杀事件都发生在SZ或BPD的背景下。非自杀病例包括SZ或BPD受试者以及无精神病诊断的受试者。我们确定了5-HT 2CR mRNA编辑变异与自杀相关，但与共病精神病诊断无关，并且不受人口统计学特征（年龄和性别）以及酒精或药物使用的影响。这些变异包括mRNA变体（ACD和ABCD）库的显著增加，这些变体编码5-HT 2CR最普遍和高度编辑的同种型之一，即VSV（Val 156-Ser 158-Val 160）。由于5-HT 2CR的VSV同种型表现出低功能活性，其表达频率的增加可能显著影响脑的多巴胺能调节。因此，至少在SZ或BPD患者中，VSV亚型在前额叶皮质的过度表达可能代表自杀行为的额外风险因素。
Suicide is a major public health problem with similar to 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.