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- Title
FKBP5 and attention bias for threat: associations with hippocampal function and shape.
- Authors
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
- Abstract
<bold>Importance: </bold>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.<bold>Objective: </bold>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.<bold>Design: </bold>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.<bold>Setting: </bold>Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia.<bold>Participants: </bold>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.<bold>Main Outcome Measures: </bold>Behavioral and fMRI (blood oxygen level-dependent) response, voxel-based morphometry, and shape analyses.<bold>Results: </bold>Carriers of the rs1360780 T allele showed an attention bias toward threat compared with individuals without 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.<bold>Conclusion: </bold>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.
- Publication
JAMA Psychiatry, 2013, Vol 70, Issue 4, p392
- ISSN
2168-622X
- Publication type
journal article
- DOI
10.1001/2013.jamapsychiatry.210