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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使用两个英国队列的初级保健记录分析难治性抑郁症的遗传和临床特征
DOI：
10.1101/2020.08.24.20178715
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fabbri C
中科院分区：
文献类型：
--
作者：
Fabbri C
难治性抑郁症（TRD）是重度抑郁症（MDD）引起的残疾的主要原因。初级保健电子健康记录提供了一种易于访问的方法来调查TRD的临床和遗传特征。从英国生物库（UKB）和EXCEED研究的初级保健记录中定义的MDD与其他抑郁症指标进行了比较，并测试了与MDD多基因风险评分（PRS）的相关性。使用处方记录，TRD定义为至少两种抗抑郁药物之间的转换，每次处方至少6周。比较了TRD和非TRD MDD病例的临床人口统计学特征、基于SNP的遗传力（h2SNP）以及与精神和非精神性状的遗传重叠。在230，096和8926名具有初级保健数据的UKB和EXCEED参与者中，MDD的患病率分别为8.7%和14.2%，其中TRD分别为13.2%和13.5%。在两个队列中，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与健康对照组和非TRD与健康对照组2SNP相当（分别为0.25 [SE = 0.04]和0.19 [SE = 0.02]）。TRD与非TRD患者的PRS呈正相关，具有较低的社会经济地位、肥胖、较高的神经质和其他不利的临床特征。本研究表明，MDD和TRD可以使用初级保健记录可靠地定义，并提供了TRD遗传，临床和人口统计学特征的首次大规模人群评估。
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 controlsh2SNPwas 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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DOI：
10.3390/ijerph15122763
发表时间：
2018-12-01
影响因子：
--
作者：
Wlodarczyk, Julian;Lawn, Sharon;Litt, John
通讯作者：
Litt, John
影响因子：
7.4
作者：
Cepeda MS;Reps J;Ryan P
通讯作者：
Ryan P
DOI：
--
发表时间：
2017-07
期刊：
--
影响因子：
--
作者：
T. Vos;A. Abajobir;C. Abbafati;K. Abbas;K. H. Abate;F. Abd-Allah;A. Abdulle;Teshome Abuka Abebo-
通讯作者：
T. Vos;A. Abajobir;C. Abbafati;K. Abbas;K. H. Abate;F. Abd-Allah;A. Abdulle;Teshome Abuka Abebo-
影响因子：
30.8
作者：
Pardiñas AF;Holmans P;Pocklington AJ;Escott-Price V;Ripke S;Carrera N;Legge SE;Bishop S;Cameron D;Hamshere ML;Han J;Hubbard L;Lynham A;Mantripragada K;Rees E;MacCabe JH;McCarroll SA;Baune BT;Breen G;Byrne EM;Dannlowski U;Eley TC;Hayward C;Martin NG;McIntosh AM;Plomin R;Porteous DJ;Wray NR;Caballero A;Geschwind DH;Huckins LM;Ruderfer DM;Santiago E;Sklar P;Stahl EA;Won H;Agerbo E;Als TD;Andreassen OA;Bækvad-Hansen M;Mortensen PB;Pedersen CB;Børglum AD;Bybjerg-Grauholm J;Djurovic S;Durmishi N;Pedersen MG;Golimbet V;Grove J;Hougaard DM;Mattheisen M;Molden E;Mors O;Nordentoft M;Pejovic-Milovancevic M;Sigurdsson E;Silagadze T;Hansen CS;Stefansson K;Stefansson H;Steinberg S;Tosato S;Werge T;GERAD1 Consortium;CRESTAR Consortium;Collier DA;Rujescu D;Kirov G;Owen MJ;O'Donovan MC;Walters JTR
通讯作者：
Walters JTR
队列概况 队列概况：电子健康、环境和 DNA 的扩展队列 (EXCEED)
DOI：
--
发表时间：
2019
期刊：
影响因子：
--
作者：
C. John;N. Reeve;R. Free;A. T. Williams;Aliki;J. Bethea;L. Barton;N. Shrine;C. Batini;R. Packer;S. Terry;B. Hargadon;Qingning Wang;C. Melbourne;E. Adams;C. Bee;K. Harrington;J. Miola;N. Brunskill;C. Brightling;J. Barwell;S. Wallace;Ron T Hsu;D. Shepherd;E. Hollox;L. Wain;M. Tobin
通讯作者：
M. Tobin