Cocaine- and amphetamine-regulated transcript peptide as a possible common biomarker for the symptoms expressed in major depressive disorders and amphetamine withdrawal syndrome

摘要

Cocaine- and amphetamine-regulated transcript peptide as a possible common biomarker for the symptoms expressed in major depressive disorders and amphetamine withdrawal syndrome Some symptoms such as anxiety and anhedonia in major depres- sive disorders (MDD) have similarities with drug-withdrawal syndrome expressed in drug addicts. Controlling these symptoms may be a key strategy for the treatment in both disorders. How- ever, the biological mechanism for these symptoms is elusive yet. Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuropeptide abundantly expressed in the brain regions involved in the pathophysiology of both psychiatric disorders. In the present study, we examined how CART peptide may involve in the expres- sion of symptoms shown in both disorders. In the first experiment, cerebrospinal fluids (CSF) were extracted from the L4-L5 or L3-L4 interspace in the subjects (23 patients with MDD and 24 healthy controls). Then, CART peptide levels were measured and analyzed for the relationships to the symptoms assessed with the 21-item Hamilton Depression Rating Scale (HDRS-21). It was found that CSF CART levels were significantly decreased in the MDD patients com- pared to the healthy controls and they have significant negative correlations with psychomotor retardation, somatic anxiety, and general somatic symptoms. In the second experiment, CART pep- tide levels were investigated in animal models with withdrawal symptoms induced by chronic amphetamine. Rats were repeat- edly administered with amphetamine, twice a day, five times, and light and dark and sucrose preference tests were conducted dur- ing the early and late withdrawal periods to measure the levels of anxiety and anhedonia, respectively. After behavioral test, CSFs were obtained from the rats, and their CART peptide levels were measured using an immunoassay kit. The correlations between behavioral scores and the levels of CART peptides are currently under analysis. Finding symptom-matched biomarkers will be use- ful for the development of treatment in both disorders. In this presentation, we will discuss the potential of CART peptides as biomarkers for some of the common symptoms of both disorders.