多巴胺D3受体基因与强迫症和抗抑郁反应有关。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2025-06-11 DOI:10.1016/j.pnpbp.2025.111428

Gwyneth Zai , Clement C. Zai , Eliza Burroughs , Paul D. Arnold , James L. Kennedy , Margaret A. Richter

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引用次数: 0

摘要

背景：强迫症（OCD）是一种常见的神经精神疾病，具有很强的遗传成分。先前的研究表明多巴胺受体基因在强迫症中的作用，而多巴胺D3受体（DRD3）基因相对被忽视。有神经生物学证据表明，D3可能参与影响强迫行为和焦虑的纹状体-皮层回路。因此，我们研究了DRD3基因变异与强迫症和5 -羟色胺再摄取抑制剂（SRI）反应的关系。方法：我们分别使用基于家庭的关联测试（FBAT）和病例对照分析，检测了318名强迫症患者（包括129个小核心家庭和196个独立独生子女病例）与196名年龄、性别和种族匹配的健康对照者的9个DRD3多态性。对发病年龄（AAO）和耶鲁-布朗强迫症量表（Y-BOCS）严重程度评分进行定量分析。结果：FBAT在多态性位点rs2399504、rs7611535、rs1394016、Ser9Gly、rs167770和rs2087017上观察到名义上显著的等位基因偏传。rs2399504、rs7611535、rs1394016、Ser9Gly和rs167770多态性与AAO相关，但与FBAT的Y-BOCS评分无关。5个多态性（rs2399504、rs7611535、rs1394016、Ser9Gly和rs167770）在等位基因/基因型分布的病例对照分析中显示出趋势。使用Haploview对多态性进行单倍型分析，揭示了与强迫症相关的几种标记组合。名义上rs167770和rs11721264与舍曲林反应正相关，经多重检验校正后仍然显著。结论：这是我们所知的第一个关于DRD3参与强迫症的报道，需要进一步的研究。

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Dopamine D3 receptor gene is associated with obsessive-compulsive disorder and antidepressant response

Background

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with a strong genetic component. Previous studies have suggested a role for the dopamine receptor genes in OCD with the dopamine D3 receptor (DRD3) gene being relatively overlooked. There is neurobiological evidence that D3 may be involved in the striatal-cortical circuits that affect compulsive behaviour and anxiety. Thus, we investigated genetic variants of DRD3 in association with OCD and serotonin reuptake inhibitor (SRI) response.

Methods

We examined nine polymorphisms across DRD3 in 318 individuals with OCD (comprised of 129 small nuclear families, and 196 independent singleton cases) compared to 196 healthy controls matched for age, gender, and ethnicity using the family-based association test (FBAT) and case-control analysis respectively. Quantitative analyses were performed with age at onset (AAO) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) severity scores.

Results

Nominally significant biased transmission of alleles in polymorphic sites rs2399504, rs7611535, rs1394016, Ser9Gly, rs167770, and rs2087017 was observed with FBAT. The rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770 polymorphisms were associated with AAO but not with Y-BOCS scores using FBAT. Five polymorphisms (rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770) showed a trend in case-control analyses for allele/genotype distributions. Haplotype analyses of the polymorphisms using Haploview revealed several combinations of markers associated with OCD. Nominally positive association between rs167770 and rs11721264 and sertraline response remained significant after correction for multiple testing.

Conclusion

This is the first report to our knowledge of involvement of DRD3 in OCD, which requires further research.

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.