Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts

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 B...

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Bibliographic Details
Published in:	Molecular psychiatry Vol. 26; no. 7; pp. 3363 - 3373
Main Authors:	Fabbri, Chiara, Hagenaars, Saskia P., John, Catherine, Williams, Alexander T., Shrine, Nick, Moles, Louise, Hanscombe, Ken B., Serretti, Alessandro, Shepherd, David J., Free, Robert C., Wain, Louise V., Tobin, Martin D., Lewis, Cathryn M.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-07-2021 Nature Publishing Group
Subjects:	45/43 631/208 692/699/476/1414 Antidepressants Attention deficit hyperactivity disorder Behavioral Sciences Biological Psychology Care and treatment Depression Depression, Mental Depressive Disorder, Major - drug therapy Depressive Disorder, Major - genetics Depressive Disorder, Treatment-Resistant - drug therapy Depressive Disorder, Treatment-Resistant - genetics Diagnosis Electronic medical records Genetic aspects Heritability Humans Medicine Medicine & Public Health Mental depression Neurosciences Neurosis Patient outcomes Pharmacotherapy Polygenic inheritance Population genetics Primary care Primary Health Care Psychiatry Single-nucleotide polymorphism United Kingdom United Kingdom United Kingdom > UK
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Summary:	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 ( h 2 SNP ) 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 h 2 SNP 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1359-4184 1476-5578
DOI:	10.1038/s41380-021-01062-9