Abstract
Major depressive disorder (MDD) is a highly prevalent and devastating psychiatric illness with strong individual and societal burdens. However, biomarkers to improve the limited preventive and therapeutic approaches are scarce. Multilevel evidence suggests that the pathophysiological involvement of sphingolipids particularly increases the levels of ceramides and the ceramide hydrolyzing enzyme, acid sphingomyelinase. The activity of secretory acid sphingomyelinase (S-ASM) and routine blood parameters were determined in the serum of patients with current (unmedicated n = 63, medicated n = 66) and remitted (n = 39) MDD and healthy subjects (n = 61). Depression severity and anxiety and their 3-weeks prospective course of treatment were assessed by psychometric inventories. S-ASM activity was not different between the four groups, did not decrease during treatment, and was not lower in individuals taking medication that functionally inhibited ASM. However, S-ASM correlated positively with depression severity only in remitted patients. High enzyme activity at inclusion predicted milder clinician-evaluated and self-rated depression severity (HAM-D, MADRS, BDI-II) and state anxiety at follow-up, and was related to stronger improvement in these scores in medicated patients. S-ASM was strongly and contrariwise associated with serum lipids in unmedicated and medicated females. These findings contribute to a better understanding of the pathomechanisms underlying depression and the development of clinical strategies and biomarkers.
Highlights
Major depressive disorder (MDD), with a lifetime prevalence of more than 10%, is a severe mood disorder and a leading cause of disability worldwide, with substantial economic consequences for the society
Based on previous data with increased lysosomal ASM in patients with major depression, which correlated with depression severity, and the lack of this effect in our moderately to severely affected patients with the current major depressive episode for secretory acid sphingomyelinase (S-ASM), we conclude that secretory and lysosomal isoforms of ASM behave differently in the context of major depression
S-ASM could not serve as a diagnostic marker for a current major depressive episode, we identified an association of high S-ASM activity with a stronger improvement of depression assessed independently by self-report and clinician’s interview in medicated patients
Summary
Major depressive disorder (MDD), with a lifetime prevalence of more than 10%, is a severe mood disorder and a leading cause of disability worldwide, with substantial economic consequences for the society. A major depressive episode (MDE) is characterized by a combination of affective, social, and somatic symptoms, such as anhedonia, anxiousness, low self-esteem, feeling of worthlessness, lack of concentration and motivation, neglect of hobbies and interests, social isolation, fatigue, sleep disturbances, and changes in appetite or weight. MDD strongly impairs psychosocial functioning and quality of life. Depression is associated with an increased mortality rate that exceeds 1.65 times that of the general population [1]. Most suicides are committed by depressed individuals [2], but clinically relevant predictors are still lacking [3,4]. Despite effective treatments for depression, the disease burden of depression is only reduced by 10–30% by curative interventions, which is largely due to limitations in diagnosis, and availability of and adherence and response to appropriate treatment [5]
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