Lysophosphatidic Acid 18:0 sn-1 in Cerebrospinal Fluid as a Potential Biomarker of Depressive Symptoms in Patients with Neuropathic Pain

Background/Objectives: Lysophosphatidic acid (LPA) is a bioactive lipid mediator implicated in neuropathic pain (NP). Depressive symptoms frequently accompany NP and adversely affect outcomes, yet objective biomarkers remain limited. This study aimed to identify cerebrospinal fluid (CSF) LPA molecular species associated with depressive symptoms in patients with NP. Methods: CSF samples were obtained from 48 patients, and LPA species, including positional isomers (sn-1 and sn-2), were quantified using liquid chromatography–tandem mass spectrometry. Depressive symptoms were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Statistical analyses were performed to evaluate associations among depressive symptoms, clinical variables, and LPA species. Results: CSF LPA18:0 was significantly associated with HADS-D scores (r = 0.380, p = 0.010), with the strongest association observed for the sn-1 isoform (r = 0.385, p = 0.009). In multivariable analysis, LPA18:0 sn-1 remained independently associated with depressive symptoms, alongside pain intensity and pain catastrophizing (R2 = 0.386). Structural equation modeling supported an association between LPA18:0 sn-1 and depressive symptoms independent of pain-related factors. Conclusions: These findings suggest that CSF LPA18:0 sn-1 may be associated with a biological dimension of depressive distress and may represent a candidate biomarker of depressive distress in NP. However, these findings should be interpreted cautiously, as the analyses were exploratory, and further validation in independent and longitudinal cohorts is warranted.