title: Anterior hippocampal dysconnectivity in posttraumatic stress disorder: a dimensional and multimodal approach.
abstract: The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global brain connectivity (GBC) termed functional GBC with global signal regression (f-GBCr) and diffusion GBC (d-GBC), in combat-exposed US Veterans with and without PTSD. Seed-based aHPC anatomical connectivity analyses were also performed. A whole-brain voxel-wise data-driven investigation revealed a significant association between elevated PTSD symptoms and reduced medial temporal f-GBCr, particularly in the aHPC. Similarly, aHPC d-GBC negatively correlated with PTSD severity. Both functional and anatomical aHPC dysconnectivity measures remained significant after controlling for hippocampal volume, age, gender, intelligence, education, combat severity, depression, anxiety, medication status, traumatic brain injury and alcohol/substance comorbidities. Depression-like PTSD dimensions were associated with reduced connectivity in the ventromedial and dorsolateral prefrontal cortex. In contrast, hyperarousal symptoms were positively correlated with ventromedial and dorsolateral prefrontal connectivity. We believe the findings provide first evidence of functional and anatomical dysconnectivity in the aHPC of veterans with high PTSD symptomatology. The data support the putative utility of aHPC connectivity as a measure of overall PTSD severity. Moreover, prefrontal global connectivity may be of clinical value as a brain biomarker to potentially distinguish between PTSD subgroups.
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Abdallah
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Wrocklage
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Averill
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: T
authors.initials: T
authors.lastname: Akiki
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schweinsburg
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Roy
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Martini
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Southwick
authors.affiliation: Clinical Neurosciences Division, VA National Center for PTSD, US Department of Veterans Affairs, West Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|VISN4 Mental Illness Research, Education, and Clinical Center, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Scott
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D000067073:Psychological Trauma / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014728:Veterans; D000067453:War Exposure