FKBP5 and attention bias for threat: associations with hippocampal function and shape.
FKBP5 and attention bias for threat: associations with hippocampal function and shape.
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FKBP5和威胁的注意力偏见：与海马功能和形状的关联。
DOI：
10.1001/2013.jamapsychiatry.210
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发表时间：
2013-04
期刊：
影响因子：
25.8
通讯作者：
Ressler, Kerry J.
中科院分区：
文献类型：
--
作者：
Fani, Negar;Gutman, David;Tone, Erin B.;Almli, Lynn;Mercer, Kristina B.;Davis, Jennifer;Glover, Ebony;Jovanovic, Tanja;Bradley, Bekh;Dinov, Ivo D.;Zamanyan, Alen;Toga, Arthur W.;Binder, Elisabeth B.;Ressler, Kerry J.
FKBP5基因产物调节糖皮质激素受体（GR）敏感性和下丘脑-垂体-肾上腺轴功能，并与许多应激相关精神疾病有关。对中间表型（如情绪加工偏差及其神经基质）的研究，为阐明FKBP5失调介导精神疾病风险的机制提供了一种途径。研究与FKBP5基因调控相关的假定功能单核苷酸多态性（rs1360780）的等位基因变异是否与威胁注意偏倚存在差异。这是通过点探测任务的行为反应和任务执行过程中的海马激活来测量的。同时还测量了海马差异反应的形态学底物。2010年至2012年在点探针上进行的横断面研究（使用功能磁共振成像[fMRI]），研究基因型、行为反应和神经反应之间的关系；基于体素的形态测量和整体和局部形状分析用于测量基因型组之间海马的结构差异。参与者是从乔治亚州亚特兰大市一家公立医院的初级保健诊所招募的。一组非裔美国成年人（N=103）按基因型分为两组：一组基因型包括rs1360780 T等位基因携带者，该等位基因与创伤后应激障碍和情感障碍的风险增加有关；另一组没有携带这种等位基因。行为学数据包括男女（N=103）；MRI队列（n=36）仅包括女性。行为和fMRI（血氧水平依赖）反应，基于体素的形态测量和形状分析。携带rs1360780 T等位基因的个体与不携带rs1360780 T等位基因的个体相比，存在对威胁的注意偏倚（F1,90=5.19， P= 0.02）。携带该等位基因的人海马的激活程度相应增加，形态也有所不同；整体和局部形状分析显示，与CC基因型组相比，TT/TC的海马形状发生了变化。FKBP5基因变异可能通过对海马结构和功能的不同影响而与压力相关精神疾病的风险相关，从而导致对感知威胁的注意力反应改变。
The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamic-pituitary-adrenal axis functioning and has been associated with many stress-related psychiatric disorders. The study of intermediate phenotypes, such as emotion-processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders. To examine whether allelic variations for a putatively functional single-nucleotide polymorphism associated with FKBP5 gene regulation (rs1360780) would relate differentially to attention bias for threat. this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphologic substrates of differential hippocampal response were also measured. Cross-sectional study conducted from 2010 to 2012 examining associations between genotype, behavioral response, and neural response (using functional magnetic resonance imaging [fMRI]) on the dot probe; voxel-based morphometry and global and local shape analyses were used to measure structural differences in hippocampi between genotype groups. Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia. An African American cohort of adults (N=103) was separated into 2 groups by genotype: one genotype group included carriers of the rs1360780 T allele, which has been associated with increased risk for posttraumatic stress disorder and affective disorders; the other group did not carry this allele. Behavioral data included both sexes (N=103); the MRI cohort (n=36) included only women. Behavioral and fMRI (blood oxygen level–dependent) response, voxel-based morphometry, and shape analyses. Carriers of the rs1360780 T allele showed an attention bias toward threat compared with individuals with-out this allele (F1,90=5.19, P=.02). Carriers of this allele demonstrated corresponding increases in hippocampal activation and differences in morphology; global and local shape analyses revealed alterations in hippocampal shape for TT/TC compared with CC genotype groups. Genetic variants of FKBP5 may be associated with risk for stress-related psychiatric disorders via differential effects on hippocampal structure and function, resulting in altered attention response to perceived threat.
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影响因子：
3.7
作者：
Anacker, Christoph;Zunszain, Patricia A.;Carvalho, Livia A.;Pariante, Carmine M.
通讯作者：
Pariante, Carmine M.
影响因子：
2.6
作者：
Fani, Negar;Jovanovic, Tanja;Ely, Timothy D.;Bradley, Bekh;Gutman, David;Tone, Erin B.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
3.7
作者：
Dinov, Ivo;Lozev, Kamen;Toga, Arthur
通讯作者：
Toga, Arthur
影响因子：
30.8
作者：
Binder, EB;Salyakina, D;Muller-Myhsok, B
通讯作者：
Muller-Myhsok, B
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.