Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts.
Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts.
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DOI：
10.1038/s41380-021-01062-9
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发表时间：
2021-07
影响因子：
11
通讯作者：
Lewis CM
中科院分区：
文献类型：
--
作者：
Fabbri C;Hagenaars SP;John C;Williams AT;Shrine N;Moles L;Hanscombe KB;Serretti A;Shepherd DJ;Free RC;Wain LV;Tobin MD;Lewis CM
难治性抑郁症（TRD）是重度抑郁症（MDD）致残的主要原因。初级保健电子健康记录提供了一种易于获取的方法来调查TRD的临床和遗传特征。从UK Biobank （UKB）和EXCEED研究的初级保健记录中定义的MDD进行了比较，并测试了与MDD多基因风险评分（PRS）的关联。使用处方记录，TRD定义为至少两次抗抑郁药物切换，每次处方至少6周。比较了TRD和非TRD MDD患者的临床人口学特征、基于snp的遗传力（h2SNP）以及与精神和非精神特征的遗传重叠。在230,096名UKB和8926名有初级保健数据的参与者中，MDD患病率分别为8.7%和14.2%，其中TRD患病率分别为13.2%和13.5%。在这两个队列中，从初级保健记录中定义的MDD与MDD PRS密切相关，在UKB中，它与其他MDD定义的重叠率为71-88%。在UKB中，TRD与健康对照、非TRD与健康对照的h2SNP具有可比性（分别为0.25 [SE = 0.04]和0.19 [SE = 0.02]）。TRD与非TRD与注意缺陷多动障碍的PRS呈正相关，具有较低的社会经济地位、肥胖、较高的神经质等不利临床特征。该研究表明，MDD和TRD可以通过初级保健记录可靠地定义，并首次对TRD的遗传、临床和人口学特征进行了大规模的人群评估。
Treatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Primary care electronic health records provide an easily accessible approach to investigate TRD clinical and genetic characteristics. MDD defined from primary care records in UK Biobank (UKB) and EXCEED studies was compared with other measures of depression and tested for association with MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least 6 weeks. Clinical-demographic characteristics, SNP-based heritability (h2SNP) and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases. In 230,096 and 8926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD, respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 71–88% with other MDD definitions. In UKB, TRD vs healthy controls and non-TRD vs healthy controls h2SNP was comparable (0.25 [SE = 0.04] and 0.19 [SE = 0.02], respectively). TRD vs non-TRD was positively associated with the PRS of attention deficit hyperactivity disorder, with lower socio-economic status, obesity, higher neuroticism and other unfavourable clinical characteristics. This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
7.4
作者：
Cepeda MS;Reps J;Ryan P
通讯作者：
Ryan P
DOI：
10.1176/appi.focus.16407
发表时间：
2018-10-01
期刊：
Focus (American Psychiatric Publishing)
影响因子：
--
作者：
Cipriani, Andrea;Furukawa, Toshi A;Geddes, John R
通讯作者：
Geddes, John R
影响因子：
7.7
作者：
John, Catherine;Reeve, Nicola F.;Tobin, Martin D.
通讯作者：
Tobin, Martin D.
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.