Identification of biological markers is extremely important to improve patient’s care in psychiatry and contributes to the development of new treatment options for anxiety and depression. However, with certain exceptions, truly sensitive and specific markers are still lacking. Several studies have reported opioid systems dysfunction in pathogenesis of anxiety and depression. Recently we have demonstrated that endomorphin-1 (EM-1: Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2), two endogenous peptides, which bind to the µ-opioid receptors with extremely high affinity and selectivity, displayed antidepressant-like effect in rodents. It has also been reported that these peptides exert anxiolytic-like action. Based on these data, we have quantified, with both HPLC and mass spectrometry methods, the brain EM-1 and EM-2 levels, in two animal models selected according to their divergences in anxiety and depression tests.
Using different behavioral paradigms, we observed important inter-individual variation of animal in vulnerability to anxiety and depression. From these observations, among the whole population of bred CD1 mice (Charles River, France), we selected: in anxiety tests, high-anxiety-related behavior “anxious, A”, low-anxiety-related behavior “non anxious, NA” and intermediate-anxiety-related behavior “intermediate, IA” mice; and in depression, high-helpless-related behavior “helpless, H”, low-helpless-related behavior “non helpless, NH” and intermediate-helpless-related behavior “intermediate, IH” mice.
Compared with “NA” and “IA” mice, “A” mice display lower basal brain EM-1 and EM-2 levels, quantified in both HPLC and mass spectrometry methods. Similarly, “H” mice display lower basal brain EM-1 and EM-2 levels than “NH” and “IH” mice. We also showed that chronic treatment of “A” mice with fluoxetine (an established antidepressant) corrected the endogenous endomorphin’s deficiency observed in this animal model.
These results provide the first evidence of cerebral deficiency of both EM-1 and EM-2 levels in physiopathology of anxiety and depression. Endomorphins could thus be used as potential biomarkers to diagnose anxiety and depressive disorders.
Supported by FDER, POLONIUM, Haute-Normandie, TC2N