STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5

• Type of Material: Article
• Authors: Negar Fani, Emory University; Tricia Z. King, Georgia State University; Jaemin Shin, Georgia Institute of Technology; Amita Srivastava, Morehouse School of Medicine; Ryan C. Brewster, Georgia State University; Tanja Jovanovic, Emory University; Bekh Bradley-Davino, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2016-04-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/da.22483
• Title of Journal or Parent Work: Depression and Anxiety
• ISSN: 1091-4269
• Volume: 33
• Issue: 4
• Start Page: 300
• End Page: 307
• Grant/Funding Information: Support was also received from Howard Hughes Medical Institute, PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Center for Research Resources, and the Burroughs Wellcome Fund (KJR).; This work was primarily supported by National Institutes of Mental Health (R01 MH071537, M01RR00039 and P20RR16435 to KJR, MH101380 to NF, MH098212 and MH092576 to TJ).
• Keywords: BDNF VAL66MET; DEPRESSION; FKBP5; connectivity; Life Sciences & Biomedicine; NETWORK CONNECTIVITY; hippocampus; MICROSTRUCTURE; Social Sciences; Psychology; RISK; FIBER TRACTOGRAPHY; diffusion tensor imaging; PTSD; Psychology, Clinical; genetics; Psychiatry; WHITE-MATTER INTEGRITY; Science & Technology; BRAIN; anterior cingulate; neuroimaging; ANOREXIA-NERVOSA

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.