title: FKBP5 and attention bias for threat: associations with hippocampal function and shape.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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: Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30329, USA.
authors: Negar
authors: N
authors: Fani
authors: David
authors: D
authors: Gutman
authors: Erin B
authors: EB
authors: Tone
authors: Lynn
authors: L
authors: Almli
authors: Kristina B
authors: KB
authors: Mercer
authors: Jennifer
authors: J
authors: Davis
authors: Ebony
authors: E
authors: Glover
authors: Tanja
authors: T
authors: Jovanovic
authors: Bekh
authors: B
authors: Bradley
authors: Ivo D
authors: ID
authors: Dinov
authors: Alen
authors: A
authors: Zamanyan
authors: Arthur W
authors: AW
authors: Toga
authors: Elisabeth B
authors: EB
authors: Binder
authors: Kerry J
authors: KJ
authors: Ressler
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000523:psychology; D000483:Alleles; D001288:Attention / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000502:physiology*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5