title: FKBP5 genotype and structural integrity of the posterior cingulum.
abstract: Alterations in the microarchitecture of the posterior cingulum (PC), a white matter tract proximal to the hippocampus that facilitates communication between the entorhinal and cingulate cortices, have been observed in individuals with psychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). PC decrements may be a heritable source of vulnerability for the development of affective disorders; however, genetic substrates for these white matter abnormalities have not been identified. The FKBP5 gene product modulates glucocorticoid receptor function and has been previously associated with differential hippocampal structure, function, and affect disorder risk. Thus, FKBP5 is an attractive genetic target for investigations of PC integrity. We examined associations between PC integrity, measured through diffusion tensor imaging (DTI) and fractional anisotropy (FA; an index of white matter integrity), and polymorphisms in the FKBP5 SNP rs1360780 in a sample of 82 traumatized female civilians. Findings indicated that, compared with individuals without this allele, individuals who carried two 'risk' alleles for this FKBP5 SNP (T allele; previously associated with mood and anxiety disorder risk) demonstrated significantly lower FA in the left PC, even after statistically controlling for variance associated with age, trauma exposure, and PTSD symptoms. These data suggest that specific allelic variants for an FKBP5 polymorphism are associated with decrements in the left PC microarchitecture. These white matter abnormalities may be a heritable biological marker that indicates increased vulnerability for the development of psychiatric disorders, such as PTSD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Negar
authors.initials: N
authors.lastname: Fani
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, GA, USA.
authors.forename: Tricia Z
authors.initials: TZ
authors.lastname: King
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Reiser
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA [2] Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Atlanta VA Medical Center, Decatur, GA, USA.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA [2] Howard Hughes Medical Institute, Chevy Chase, MD, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000367:Age Factors; D016880:Anisotropy; D054022:Cerebrum / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000473:pathology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5