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Depress Anxiety. 2016 Apr;33(4):300-7. doi: 10.1002/da.22483.

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

Author information

1
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
2
Department of Psychology, Georgia State University, Atlanta, Georgia.
3
Georgia Institute of Technology, Atlanta, Georgia.
4
Morehouse School of Medicine, Atlanta, Georgia.
5
Atlanta VA Medical Center, Decatur, Georgia.

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.

KEYWORDS:

FKBP5; PTSD; anterior cingulate; connectivity; diffusion tensor imaging; genetics; hippocampus; neuroimaging

PMID:
27038411
PMCID:
PMC4983452
DOI:
10.1002/da.22483
[Indexed for MEDLINE]
Free PMC Article

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