Document Detail


FKBP5 and attention bias for threat: associations with hippocampal function and shape.
MedLine Citation:
PMID:  23407841     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE: 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.
OBJECTIVE: 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.
DESIGN: 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.
SETTING: Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia.
PARTICIPANTS: 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.
MAIN OUTCOME MEASURES: Behavioral and fMRI (blood oxygen level-dependent) response, voxel-based morphometry, and shape analyses.
RESULTS: 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.
CONCLUSION: 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.
Authors:
Negar Fani; David Gutman; Erin B Tone; Lynn Almli; Kristina B Mercer; Jennifer Davis; Ebony Glover; Tanja Jovanovic; Bekh Bradley; Ivo D Dinov; Alen Zamanyan; Arthur W Toga; Elisabeth B Binder; Kerry J Ressler
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-31     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  392-400     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
African Americans / genetics,  psychology
Alleles
Attention / physiology*
Cross-Sectional Studies
Female
Functional Neuroimaging
Genotype
Hippocampus / anatomy & histology,  physiology*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics
Stress, Psychological / genetics,  physiopathology
Tacrolimus Binding Proteins / genetics,  physiology*
Young Adult
Grant Support
ID/Acronym/Agency:
F32MH095456/MH/NIMH NIH HHS; M01RR00039/RR/NCRR NIH HHS; R01 MH071537/MH/NIMH NIH HHS; R01MH071537/MH/NIMH NIH HHS; R21 MH098212/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
EC 5.2.1.-/Tacrolimus Binding Proteins; EC 5.2.1.8/tacrolimus binding protein 5
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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