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注意缺陷多动障碍亚型及治疗抵抗病例中的基因变异

Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases.

作者信息

Unal Dilek, Unal Mehmet Fatih, Alikasifoglu Mehmet, Cetinkaya Arda

机构信息

Department of Child and Adolescent Psychiatry, Hacettepe University School of Medicine, Ankara, Turkey.

Department of Medical Genetics, Hacettepe University School of Medicine, Ankara, Turkey.

出版信息

Psychiatry Investig. 2016 Jul;13(4):427-33. doi: 10.4306/pi.2016.13.4.427. Epub 2016 Jul 25.

Abstract

OBJECTIVE

ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity.

METHODS

Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group.

RESULTS

Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis.

CONCLUSION

Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.

摘要

目的

我们评估了α-2A肾上腺素能受体(ADRA2A)和儿茶酚-O-甲基转移酶(COMT)单核苷酸多态性(SNP)在注意缺陷多动障碍(ADHD)各亚型以及其他同质患者群体(包括治疗抵抗病例和症状严重程度高的患者)中的分布情况。

方法

本研究纳入了121名6至18岁的ADHD患者。使用儿童情感障碍和精神分裂症评定量表(K-SADS)确认诊断和亚型分类,并使用康纳斯父母评定量表(CPRS)和教师评定量表(CTRS)评估症状。使用临床总体印象-严重程度量表(CGI-S)、功能总体评定量表(GAS)以及连续操作测试(CPT)和连线测验(TMT-A、B)客观评估对哌甲酯的反应。通过聚合酶链反应/限制性片段长度多态性(PCR/RFLP)对患者的ADRA2A(rs1800544)和COMT(rs4680)SNP进行基因分型,并与性别匹配的对照组进行比较。

结果

虽然COMT(rs4680)SNP与症状或诊断无关,但在逻辑回归分析中,ADRA2A多态性、低社会经济地位(SES)和共病精神诊断均与对哌甲酯的反应不佳有关。

结论

当存在这些负面因素时,临床医生在未来可能会考虑辅助策略,以提高ADHD个体化治疗的成功率。

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