Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)
Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)
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DOI：
10.1038/sj.tpj.6500301
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Yébenes, JG
中科院分区：
文献类型：
--
作者：
Barrero, FJ;Ampuero, I;Yébenes, JG
抑郁是帕金森病（PD）的常见症状，高达40%的患者存在抑郁。PD患者抑郁的原因被认为与单胺类神经递质障碍有关。内源性大麻素系统介导不同的大脑过程，在控制行为和情绪方面发挥作用。大麻素的功能可能会改变神经精神疾病，直接或通过与单胺，GABA和谷氨酸系统的相互作用。为此，我们研究了PD患者中是否存在与CB1受体基因多态性相关的抑郁症遗传危险因素。抑郁症在PD患者中比在骨关节炎对照组中更常见。抑郁症的存在与疾病的分期无关，但在单纯运动不能综合征患者中比震颤型或混合型PD患者更常见。CB1受体基因多态性（AAT）n被认为可以改变基因的转录，因此可能具有功能相关性。我们分析了89名受试者（48名PD患者和41名对照）编码CB1（CNR1）受体的基因的多态性三联体（AAT）n的长度。在PD患者中，CNR1基因中存在两个长等位基因，具有超过16个重复AAT三核苷酸，与抑郁症患病率降低相关（Fisher精确检验：P = 0.003）。这种关联在对照组中没有达到显著差异，但对照组中患有抑郁症的人数太少，无法进行统计分析。由于具有长扩展的等位基因可能在大麻素神经传递中具有功能性影响，因此我们的数据表明大麻素神经传递的药理学操作可以为PD和可能的其他条件下的抑郁症的治疗开辟一种新的治疗方法。
Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT) n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet ( AAT) n of the gene that encodes CB1 (CNR1) receptor in 89 subjects ( 48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression ( Fisher's exact test: P = 0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.