White matter microstructure of the uncinate fasciculus is associated with subthreshold posttraumatic stress disorder symptoms and fear potentiated startle during early extinction in recently deployed Service Members.

Early intervention following combat deployment has the potential to prevent posttraumatic stress disorder (PTSD), but there is a need for greater understanding of the factors that contribute to PTSD symptom progression. This study investigated: (1) fear-potentiated startle during a fear extinction, (2) white matter microstructure, and (3) PTSD symptom severity, in 48 recently deployed service members (SMs) who did not have sufficient PTSD symptoms to meet criteria for a clinical diagnosis. Electromyography startle during a conditional discrimination paradigm, diffusion tensor imaging, and the Clinician Administered PTSD Scale were assessed in a cohort of SMs within 2 months after their return from Iraq or Afghanistan. Significant correlations were found between left uncinate fasciculus (UF) white matter tract integrity and total PTSD symptoms, r=-0.343, p=0.018; the left UF and hyperarousal symptoms, r=-0.29, p=0.047; right UF integrity and total PTSD symptoms r=-0.3371, p=0.01; right UF integrity and hyperarousal symptoms r=-0.332, p=0.023; left UF and startle during early extinction, r=.31, p=0.033. Our results indicate that compromise of UF tract frontal-limbic connections are associated with greater PTSD symptom severity and lower startle response during extinction. In a subthreshold population, such a relationship between brain structure, physiological reactivity, and behavioral expression may reveal vulnerabilities that could have significant implications for PTSD symptom development.