Psychosomatic - psychotherapeutic treatment of stress-related disorders impacts the sphingolipid metabolism towards increased sphingosine and sphingosine-1-phosphate levels

Abstract

Objective

Chronic stress is a risk factor for developing stress-induced mental disorders like major depression and post-traumatic stress disorder. Low-grade inflammatory processes seem to mediate this association. The sphingolipid metabolism with its most important lipid messengers ceramide and sphingosine-1-phosphate (S1P) was shown to play an important role in the pathophysiology of affective disorders and inflammation.

Method

We conducted an exploratory trial to investigate the effect of intensive psychosomatic - psychotherapeutic treatment of stress-induced disorders on the biological level. Before and after eight weeks of treatment, blood plasma of 67 patients was analyzed for sphingolipid levels and their metabolizing enzymes. Symptom severity of depression (PHQ-9), anxiety (GAD-7), and somatization (PHQ-15) was assessed in parallel.

Results

During psychosomatic - psychotherapeutic treatment, symptom severity of depression, anxiety, and somatization decreased significantly. Levels of the stress molecule cortisol decreased upon treatment. Enzymatic activities of secreted acid sphingomyelinase (S-ASM) and neutral sphingomyelinase (NSM) increased significantly upon treatment, as well as of neutral ceramidase (NC). Regarding the lipid level, the molar ratio of ceramide species Cer16:0 and Cer18:0 decreased upon treatment, whereas sphingosine and S1P levels increased.

Conclusions

Psychosomatic – psychotherapeutic treatment was associated with a reduction in specific ceramide ratios and an increase in sphingosine and S1P levels potentially resulting from increased activity of sphingolipid metabolizing enzymes. Stress-induced mental disorders might be associated with disturbed sphingolipid levels that seem to be balanced during psychosomatic treatment. This study offers a further piece of evidence that the sphingolipid metabolism could be involved in the pathophysiology of stress-induced disorders, and its analysis could be helpful for treatment monitoring.