کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6226952 1276415 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder
ترجمه فارسی عنوان
تغییر تعداد کپی ریز در اختلال افسردگی عمده مقاوم در درمان
کلمات کلیدی
ضد افسردگی، شماره کپی، حذف، تکثیر، داروهای گیاهی فارماکولوژیک تنوع ژنتیکی نادر،
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
چکیده انگلیسی

BackgroundWhile antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD).MethodsWe analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial.ResultsCNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100-200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction.ConclusionsContribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 76, Issue 7, 1 October 2014, Pages 536-541
نویسندگان
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