In this study, we demonstrated that the serum LC and ALC concentrations were significantly lower in patients with MDD than those in the HC group. The concentration of ALC was negatively correlated with the severity of MDD in patients with moderate to severe MDD. The results of the ROC analysis revealed an AUC of 0.6943 with 61.0% sensitivity and 74.0% specificity for LC and an AUC of 0.8496 with 67.0% sensitivity and 93.0% specificity for ALC in differentiating patients with MDD from those in the HC group. In the effective-treatment group, the concentration of LC and ALC in patients with depression was significantly increased after treatment with antidepressants. However, there was no significant change in the ineffective-treatment group. These results suggest that ALC and LC may be diagnostic and therapeutic markers of depression.
LC is a nonessential amino acid derived from the essential amino acids lysine and methionine, whose balance is maintained through dietary intake and endogenous formation followed by renal excretion [29]. In the brain, LC and its derivative ALC are present in high concentration, reducing nerve damage by regulating mitochondrial permeability and preventing excitatory toxicity [30]. LC and ALC may play different roles in depression, from metabolism [31] and neurochemistry [32–33] to epigenetic roles [34–36]. In agreement with the results obtained using a depression rodent model and clinical MDD samples studied by Nasca et al. [28], the ALC level in patients with MDD was significantly lower than that of the age- and gender-matched HC group, and a negative correlation between the ALC levels and HDRS-24 scores was found in the present study. A previous contribution reported a positive correlation between ALC concentrations in peripheral blood and the central nervous system [37]. Based on the ROC analysis, the serum ALC cut-off point of 1.54 µg/mL showed a 67.0% sensitivity and a 93.0% specificity, indicating that serum ALC has a superior diagnostic value (AUC = 0.8496) in MDD.
In contrast to the above clinical study [28], we found that there was a significant difference in LC levels between patients with MDD and HC. This difference may be due to race, sample size, and eating habits. The Pearson correlation analysis showed that there was no correlation between HDRS-24 scores and serum LC concentrations, and the AUC for LC was less than 0.7. These results suggest that LC is closely related to depression, but may not be suitable as a biomarker of MDD. About 75% of the human carnitine is derived from exogenous carnitine (mainly from meat and dairy products), and further research is needed to assess whether the decrease of LC and ALC levels in patients with MDD is sensitive to unhealthy lifestyle choices, such as lack of exercise, poor diet, smoking, and lack of adequate sleep.
Many clinical studies [38–39] have confirmed that ALC can significantly reduce the symptoms of depression compared with the established antidepressants and has similar effectiveness. However, no studies have reported the changes of LC and ALC levels in patients after treatment with antidepressant drugs. To verify the correlation between the level of LC and ALC and the outcome of depression, we compared the changes of LC and ALC in patients with depression before and after treatment. In the treatment group with a HDRS-24 score reduction rate greater than 50%, the content of ALC and LC increased significantly after treatment with antidepressant drugs. There was no significant change in the concentration of ALC and LC in the ineffective-treatment group. These results show that the concentration of LC and ALC are related to the therapeutic effect of depression. Due to the impact of the new coronavirus pneumonia, we stopped collecting blood samples from patients with MDD, and this resulted in a very small sample size after treatment, especially in the ineffective-treatment group. We expect to further expand the sample size and compare the effects of different types of antidepressants on LC and ALC concentrations in patients with depression.
LC and ALC are transformed into each other in the body. Carnitine acetyltransferase catalyzes the synthesis of acetyl-CoA (CoA) and L-carnitine on the mitochondrial inner membrane, and enters the mitochondrial matrix through the carnitine/acetylcarnitine acyltransferase. Carnitine penetrates the mitochondrial matrix and there, the carnitine acetyltransferase converts acylcarnitine to carnitine and acetyl CoA [40]. Since LC and ALC are transformed into each other in the body, they are obviously negatively correlated in depression patients, and their contents are closely related to the onset and outcome of depression. LC and ALC might be considered as potential biomarkers of depression at the same time. Unexpectedly, LC and ALC showed a significant positive correlation in patients with MDD, but there was no such correlation in HC. The correlation in patients with MDD may be related to the onset of depression, and further research is needed to confirm this assumption.
This study has several limitations. First, the study is a single-center study with a small sample size. Second, the effects of diet, exercise, sleep, and other external factors on LC and ALC concentrations were not considered. Third, the effects of different drugs on the LC and ALC concentrations after treatment were not considered.