Ảnh hưởng của kiểu gen COMT đến khả năng gắn kết của thụ thể serotonin-1A được nghiên cứu bằng PET

Brain Structure and Function - Tập 219 - Trang 2017-2028 - 2013
Pia Baldinger1, Andreas Hahn1, Markus Mitterhauser2, Georg S. Kranz1, Marion Friedl3,4, Wolfgang Wadsak2, Christoph Kraus1, Johanna Ungersböck2, Annette Hartmann3, Ina Giegling3, Dan Rujescu3,4, Siegfried Kasper1, Rupert Lanzenberger1
1Functional, Molecular and Translational Neuroimaging Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
2Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
3Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany
4Department of Psychiatry, University of Halle, Halle, Germany

Tóm tắt

Sự thay đổi của thụ thể serotonin-1A ức chế (5-HT1A) là một phát hiện vững chắc trong nghiên cứu tâm thần, đặc biệt là trong lĩnh vực các rối loạn tâm trạng và lo âu. Nhiều yếu tố ảnh hưởng đến mật độ của thụ thể này đã được xác định, chẳng hạn như hormone steroid, ánh sáng mặt trời và các biến thể di truyền của các gen liên quan đến serotonin. Với sự tương tác chặt chẽ giữa truyền dẫn thần kinh serotonergic và dopaminergic, chúng tôi đã điều tra xem một đa hình nucleotide đơn phổ biến của gen catechol-O-methyltransferase (COMT) (VAL158MET hoặc rs4680), mã hóa cho một enzym chính của mạng dopamine có liên quan đến sinh bệnh học của các rối loạn tâm trạng và phản ứng với điều trị bằng thuốc chống trầm cảm, có ảnh hưởng trực tiếp đến tiềm năng gắn kết của thụ thể 5-HT1A hay không. Năm hai cá nhân khỏe mạnh (38 nữ, tuổi trung bình ± độ lệch chuẩn = 40.48 ± 14.87) đã được đo lường thông qua chụp cắt lớp phát xạ positron (PET) bằng cách sử dụng radioligand [carbonyl-11C]WAY-100635. Phân gen cho rs4680 được thực hiện bằng cách sử dụng DNA tách ra từ máu toàn phần với nền tảng MassARRAY của phần mềm SEQUENOM®. Phân tích ANOVA voxel toàn bộ não cho thấy ảnh hưởng chính của kiểu gen đến sự gắn kết của 5-HT1A. So với các cá nhân mang gen A (AA + AG) của rs4680, các cá thể đồng hợp tử G cho thấy khả năng gắn kết 5-HT1A cao hơn ở vỏ não cingulate sau (F (2,49) = 17.7, p = 0.05, hiệu chỉnh FWE), vỏ não orbitofrontal, vỏ não cingulate trước, đảo, hạch hạnh nhân và hippocampus (mức voxel: p < 0.01 chưa hiệu chỉnh, t > 2.4; mức cụm: p < 0.05 hiệu chỉnh FWE). Đối với những thay đổi thường được báo cáo về việc gắn kết 5-HT1A trong các rối loạn lo âu và tâm trạng, nghiên cứu này đề xuất một ý nghĩa tiềm năng của kiểu gen COMT, cụ thể hơn là đa hình VAL158MET, thông qua việc điều chỉnh truyền dẫn thần kinh serotonergic.

Từ khóa

#COMT genotype #serotonin-1A receptor #PET #mood disorders #anxiety disorders #neurotransmission

Tài liệu tham khảo

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