This study revealed a significant correlation between nutritional status and depressive symptoms according to the PG-SGA and HSDS-D subscale scores in patients with HCC undergoing TACE. In addition, the PLR and SII were correlated with depression. Multiple linear regression showed that the PG-SGA was correlated with depression, whereas PLR and SII were not significantly correlated with depressive symptoms. The mechanism underlying the association between nutrition and depression does not seem to be straightforward. The interaction effect between the PG-SGA score and the PLR or SII was not significantly different, suggesting no synergistic effects in predicting depression.
Our study found that 89.5% of the patients were malnourished. Recently, similar proportions of patients with malnutrition as determined by the PG-SGA score was also reported in populations of patients with advanced lung cancer, gastric cancer and esophageal cancer (86.7%, 71.6%, and 83.8%, respectively) [28–30]. Furthermore, the prevalence of depression was 58.5%, which is similar to the results of previous studies conducted in advanced lung cancer or colorectal cancer patients [31, 32]. This suggests that there is a need to examine nutritional status and mental health to support the selection of interventions aimed at reducing the incidences of malnutrition and depression.
As expected, our observation suggested a positive correlation between nutritional status and depression, which is in agreement with the results in previous studies [33, 34]. Chabowski, Mariusz et al. assessed nutritional status using the Mini-Nutritional Assessment questionnaire and identified that better nutritional status was significantly associated with lower levels of depression in patients with lung cancer [33]. More recently, Sánchez-Torralvo, Francisco José et al. reported that depressive symptoms were 6.29 times more common in malnourished patients assessed with Global Leadership Initiative on Malnutrition criteria than in well-nourished patients [34]. Therefore, there may be some interaction between these factors.
In our study, Spearman’s correlation analysis showed that the PG-SGA score was not correlated with the NLR, PLR or SII. This contradicts the finding in the Cai et al. study that showed that the PG-SGA score was positively connected with the NLR and C-reactive protein level in patients with chronic radiation enteritis [16]. A study also showed that the PLR and NLR were negatively associated with nutrition in patients with colorectal cancer [35]. The inconsistency of these findings might be due to the investigation of different types of disease or differences in disease severity, which should be further confirmed.
Current insight into the effects of inflammation on psychological factors suggests that agents such as chemotherapeutic drugs, which can act as a trigger for inflammation, could specifically cause mental disorders [36, 37]. With respect to depressive symptoms, in accordance with the above conclusions, we also found that the PLR and SII were associated with depression. Therefore, a high PLR and high SII could be early indicators of depression in patients undergoing TACE, and the early detection of depression may improve patient quality of life. This will also help researchers determine how the inflammatory response interacts with depressive symptoms, promoting our understanding of the etiopathogenesis of depression.
Previously, evidence has shown that a higher NLR was positively associated with increased severity of depression symptoms and worse nutritional status in patients with cancer [38, 39]. However, our study found that there was no association of the NLR with depression or nutrition, which may be due to the fact that immune-related genes affect those relationships [40]. Interestingly, the NLR, an inflammatory marker, has recently been studied as a prognostic factor for survival in HCC patients who have undergone TACE [41, 42].
Nutritional status is associated with depressive symptoms because the microbiome and its metabolites affect brain activity and cognitive functions via the microbiota-gut-brain axis [43]. There are several information exchange networks, including the endocrine, central nervous, and immune systems, that connect the gut and brain. Meanwhile, the dysregulation of gamma-aminobutyric acid, serotonin, and dopamine levels was found to be connected with the pathogenesis of depression. Therefore, the interaction between nutritional status and depressive disorders could be the result of gut microbial-mediated neurotransmitter or neurotransmitter precursors entering the blood circulation and affecting the neuronal activity and cognitive functions of the brain. Some neurotransmitter precursors can pass through the blood–brain barrier and participate in the synthesis cycle of various neurotransmitters in the brain. Some neurotransmitters, such as glutamate and serotonin, can transmit sensory signals to the brain via the vagal pathway, all of which may lead to alterations in brain function and behavior [43, 44]. Evidence has shown that the abnormal expression and function of serotonin is related to the pathogenesis of anxiety-depressive disorder [45].