Reduced Serum and Cerebrospinal Fluid Levels of Autotaxin in Major Depressive Disorder

Abstract

Background: The autotaxin/lysophosphatidic acid axis is involved in diverse biological processes including neurodevelopment, inflammation, and immunological functioning. The lysophosphatidic acid 1 receptor has been implicated in the pathophysiology of major depressive disorder and in the mechanism of action of antidepressants. However, it is unclear whether central or peripheral autotaxin levels are altered in patients with major depressive disorder.

Methods: Serum autotaxin levels were measured by an enzyme-linked immunosorbent assay in 37 patients with major depressive disorder diagnosed using DSM-IV-TR who underwent electroconvulsive therapy and were compared with those of 47 nondepressed controls matched for age and sex between January 2011 and December 2015. Patient serum levels of autotaxin before and after electroconvulsive therapy were also compared. In a separate sample set, cerebrospinal fluid autotaxin levels were compared between 26 patients with major depressive disorder and 27 nondepressed controls between December 2010 and December 2015. A potential association was examined between autotaxin levels and clinical symptoms assessed with the Hamilton Depression Rating Scale.

Results: Before electroconvulsive therapy, both serum and cerebrospinal fluidautotaxin levels were significantly lower in major depressive disorder patients than in controls (serum: P = .001, cerebrospinal fluid: P = .038). A significantly negative correlation between serum, but not cerebrospinal fluid, autotaxin levels and depressive symptoms was observed (P = .032). After electroconvulsive therapy, a parallel increase in serum autotaxin levels and depressive symptoms improvement was observed (P = .005).

Conclusion: The current results suggest that serum autotaxin levels are reduced in a state-dependent manner. The reduction of cerebrospinal fluidautotaxin levels suggests a dysfunction in the autotaxin/lysophosphatidic acid axis in the brains of patients with major depressive disorder.

Keywords: autotaxin; cerebrospinal fluid; electroconvulsive therapy; lysophosphatidic acid; major depressive disorder.

Figure 1.

Scatter plot of serum levels of autotaxin (ATX) (A) before a course of electroconvulsive therapy (ECT) and cerebrospinal fluid (CSF) levels of ATX (B) in control group (female: ▲; male: △) and major depressive disorder (MDD) group (female: ●; male: ○). Serum samples (Set 1) and CSF samples (Set 2) were collected from separate facilities. The horizontal bars represent the mean values adjusted for gender. *P < .05.

Figure 2.

Correlation between serum levels of autotaxin (ATX) before a course of electroconvulsive therapy (ECT) and total Hamilton Depression Rating Scale-17 (HDRS) score in patients with major depressive disorder (MDD). The correlation coefficient was calculated by linear regression. Female values (●), n = 22; male values (○), n = 15. The dashed line represents the approximate correlation curve adjusted for gender. *P < .05.

Figure 3.

(A) Serum levels of autotaxin (ATX) before and after a course of electroconvulsive therapy (ECT) in the major depressive disorder (MDD) group, Set 1. (B) Correlation between serum levels of ATX and total Hamilton Depression Rating Scale-17 (HDRS) score at Pre/Post-ECT in the MDD group, Set 1. The correlation coefficient was calculated by linear regression. Pre-ECT female values (●), n = 17; male values (○), n = 13. Post-ECT female values (■), n = 17; male values (□), n = 13. The horizontal bars represent mean values. The dashed line represents the approximate correlation curve adjusted for gender. *P < .05.