Biological profiling of plasma neuropeptide Y in relation to posttraumatic stress symptoms in two combat cohorts

Military personnel have an increased risk of developing stressrelated mental health problems after deployment to a combat zone [1]. In order to decrease the risk of developing stress-related disorders, biological vulnerability and protective factors should be identified. Neuropeptide Y (NPY) is a peptide transmitter that is associated with modulation of the stress response. Previous studies reported reduced NPY levels in the cerebrospinal fluid (CSF) of patients with posttraumatic stress disorder (PTSD) [2]. In the periphery NPY levels were either reduced [3] or did not differ from healthy controls [4].

Instead of comparing participants based of the level of reported symptoms, the current study used a biological profiling perspective to assess NPY as a susceptibility marker for the development of PTSD symptoms. The aim was to investigate the association between biological abnormalities in plasma NPY levels prior to or in reaction to traumatic experiences and the development of PTSD symptoms over time. This study is part of a longitudinal prospective study on the development and course of stress-related mental health problems in Dutch military personnel after deployment. Data collection (N = 892) started prior to a 4-month deployment to Afghanistan and follow-up assessments were completed up to two years postdeployment.

Plasma NPY levels were determined before and shortly after deployment. In an attempt to replicate the findings, the analyses were repeated in an independent military cohort study (N = 2427) [5]. In both cohort studies similar findings were observed. Latent growth mixture modeling was performed to identify distinct classes of plasma NPY levels over time. Three plasma NPY trajectories were identified; namely a low class, a slightly decreasing intermediate class, and a high class. Following this, a series of mixed models showed that neither pre-deployment plasma NPY levels nor the NPY trajectories were related to the development of PTSD symptoms over time.

In the posthoc analyses NPY levels were also not found to differ between participants with (a high level of symptoms of) PTSD and a relatively resilient group. Additionally, neither deployment-related trauma nor early life trauma moderated the relation between the NPY trajectories and PTSD symptoms over time. While heightened NPY levels are proposed to be involved in the resiliency to stress, potentially decreasing the risk of developing stress-related disorders, the current findings suggest that basal plasma NPY levels are not a susceptibility marker for the development of PTSD symptoms from pre-deployment up to two-years post-deployment.

While our findings cannot address the utility of plasma collected contiguous to a severe stress challenge, such as military training, our findings underline the difference between peripherally and centrally measured NPY. In conclusion, this study provided important novel information on the limited usefulness of peripherally measured NPY as a susceptibility marker for the development of PTSD over a longer, pre- to post-deployment timeframe.