PLASMA LIPID AND FATTY ACID CONCENTRATIONS IN PATIENTS WITH POSTTRAUMATIC STRESS DISORDER (PTSD) AND HEALTHY INDIVIDUALS: ASSOCIATIONS WITH DIAGNOSIS, SYMPTOMS, AND INFLAMMATORY MARKERS
Authors: Ogawa *Shintaro , Hori Hiroaki , Niwa Madoka , Itoh Mariko , Lin Mingming , Yoshida Fuyuko , Ino Keiko , Kawanishi Hitomi , Narita Megumi , Nakano Wakako , Imai Risa , Matsui Mie , Kamo Toshiko , Kunugi Hiroshi , Kim Yoshiharu 
Published: February 2025

Abstract

Background
Posttraumatic stress disorder (PTSD) is a severe psychiatric condition resulting from a traumatic event, affecting both mental and physical health and impairing cognitive function. Lipid- related molecules, such as cholesterol and fatty acids, are crucial in the central nervous system (CNS), and their alterations can influence CNS functions related to PTSD symptoms. However, there is a scarcity of case-control studies examining the connection between plasma lipid-related molecules and PTSD.

Aims & Objectives
We aimed to delve into the link between lipid-related molecules and PTSD, exploring pathophysiology, inter-group variations, and their associations with background factors, psychological functions, PTSD symptoms, and plasma inflammation markers. Additionally, we aimed to assess the potential of lipid-related molecules for subject subtyping and investigate lipid profiles, psychological features, and symptomatic patterns using latent profile analysis (LPA).

Method
We examined 165 participants, comprising 67 PTSD patients and 98 healthy controls without trauma exposure. We assessed PTSD symptoms in patients using the DSM-IV version of the Posttraumatic Diagnostic Scale (PDS-IV). Childhood trauma was gauged through the Childhood Trauma Questionnaire (CTQ), and cognitive function was appraised using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for all subjects. Venous blood was collected around noon, and plasma samples were analyzed for lipid-related molecules and inflammatory cytokine levels at SRL Inc (Tokyo, Japan). We considered a two-tailed P-value of &lt;0.01 as statistically significant in all analyses, except for LPA, where a significance level of P &lt;0.05 was employed due to its highly exploratory nature.

Results
PTSD patients exhibited significantly lower plasma HDL cholesterol and n-6 linoleic acid levels, as well as higher plasma saturated palmitic acid and Triene/Tetraene (T/T) ratio compared to healthy controls. Hyperarousal symptoms (PDS category D scores) in PTSD patients were significantly positively associated with plasma levels of γ-linolenic (P = 2.5E-5), dihomo-γ-linolenic, mead acids, and the T/T ratio. Plasma γ-linolenic acid levels also showed significant positive correlations with PDS total scores. CTQ scores were significantly negatively correlated with plasma LDL cholesterol levels. Cognitive function, as assessed by RBANS scores, had positive associations with docosahexaenoic acid, n-3 fatty acids, and linoleic acid, but negative associations with dihomo-γ-linolenic, palmitic, and saturated fatty acids. Inflammation-related plasma markers were significantly correlated with plasma oleic (P = 1.9E-5), palmitic, and n-9 fatty acids, while linoleic and polyunsaturated fatty acids displayed opposite correlations. LPA analysis identified variations in plasma lipid and fatty acid profiles, including high linolenic n-6 fatty acids, suitable for subtyping PTSD patients.

Discussion & Conclusion
This study underscores the importance of plasma lipid and fatty acid alterations in PTSD patients, potentially connected to pathophysiology and symptoms, providing a foundation for further research. Additionally, we have identified unique plasma lipid and fatty acid profiles for subtyping patients with PTSD.