title: STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5.
abstract: BACKGROUND
  The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5. This was the goal of the present study.
  
  
  METHODS
  Fifty-four women with and without PTSD underwent diffusion tensor imaging and resting-state MRI. Probabilistic tractography was used to examine ACC-hippocampal structural connectivity; mean fractional anisotropy (FA) values were extracted from connectivity streamlines, which represent the cingulum bundle. Genotype data were collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780.
  
  
  RESULTS
  Participants with PTSD demonstrated poorer structural connectivity (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P < .05). An interaction of FKBP5 genotype and diagnostic group was also observed (F1, 37 = 4.52, P = .04), indicating lower cingulum FA in carriers of two risk alleles for this SNP, compared to other diagnostic and genotype groups. Carriers of two FKBP5 risk alleles also demonstrated poorer hippocampus-ACC connectivity at rest (P < .05). When cingulum FA was used a regressor in a brain-wide, seed-based regression analysis, significant associations were found between the hippocampus and dorsal regions of the ACC (P < .05).
  
  
  CONCLUSIONS
  Individuals with PTSD demonstrated compromised structural connectivity of the hippocampus-ACC pathway. Altered hippocampus-ACC connectivity may represent a highly salient intermediate neural phenotype for PTSD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Negar
authors.initials: N
authors.lastname: Fani
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, Georgia.
authors.forename: Tricia Z
authors.initials: TZ
authors.lastname: King
authors.affiliation: Georgia Institute of Technology, Atlanta, Georgia.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Shin
authors.affiliation: Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Amita
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Psychology, Georgia State University, Atlanta, Georgia.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Brewster
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.|Atlanta VA Medical Center, Decatur, Georgia.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000523:psychology / Q000706:statistics & numerical data; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D054022:Cerebrum / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000503:physiopathology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; 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
keywords: FKBP5; PTSD; anterior cingulate; connectivity; diffusion tensor imaging; genetics; hippocampus; neuroimaging