The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning

被引:21
作者
Kautzky, A. [1 ]
James, G. M. [1 ]
Philippe, C. [2 ]
Baldinger-Melich, P. [1 ]
Kraus, C. [1 ]
Kranz, G. S. [1 ]
Vanicek, T. [1 ]
Gryglewski, G. [1 ]
Wadsak, W. [2 ,3 ]
Mitterhauser, M. [2 ,4 ]
Rujescu, D. [5 ]
Kasper, S. [1 ]
Lanzenberger, R. [1 ]
机构
[1] Med Univ Vienna, Dept Psychiat & Psychotherapy, Wahringer Gurtel 18-20, A-1090 Vienna, Austria
[2] Med Univ Vienna, Div Nucl Med, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria
[3] Ctr Biomarker Res Med CBmed, Graz, Austria
[4] Ludwig Boltzmann Inst Appl Diagnost, Vienna, Austria
[5] Martin Luther Univ Halle Wittenberg, Univ Clin Psychiat Psychotherapy & Psychosomat, Halle, Germany
基金
奥地利科学基金会;
关键词
POSITRON-EMISSION-TOMOGRAPHY; 5-HT1A RECEPTOR; ANTIDEPRESSANT RESPONSE; 1A BINDING; IN-VIVO; HETERORECEPTOR COMPLEXES; C(-1019)G POLYMORPHISM; PROMOTER POLYMORPHISM; AMYGDALA REACTIVITY; DNA METHYLATION;
D O I
10.1038/tp.2017.108
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl-C-11] WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BPND) was divided by dorsal raphe BPND as a specific measure to highlight rs6295 effects (BPDiv). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BPDiv was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT1A BPND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.
引用
收藏
页码:e1150 / e1150
页数:9
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