Depression is a common psychiatric disorder, with high recurrent rate and high morbidity in the whole world (Monroe and Harkness 2022). Epidemiological investigations have proposed that depression could be a major cause of disease burden by 2030 (Malhi and Mann 2018). Depression and obesity are major public implications that tend to appear within individuals. The presence of obesity could induce the development of depressive symptoms, vice versa (Milaneschi et al., 2019) It has become essential to understand the interactive mechanism between depression and obesity. The previous study had brought forward some co-existing biological pathways between these two diseases, including neuroendocrine regulators, genetics, immune-inflammatory activation, mood regulatory responses and adipokines (leptin, adiponectin) (Carvalho et al., 2014).

Recent studies have revealed that patients with mental illness have metabolic disturbance of adipokines, including lower leptin levels and chemerin and higher adiponectin and resistin levels compared to controls (Veru-Lesmes et al., 2021). C1q/TNF-related proteins (CTRPs) secreted by adipose tissue is an emerging member of the adipokines family in recent years (Seldin et al., 2014). CTRPs assume a homotrimeric structure and each subunit is composed of a short variable region, an N-terminal signal peptide and a C-terminal C1q globular domain.

Until now, The CTRPs have been demonstrated to be involved in the regulation of many physiological and pathological processes in the body. For example, the injection of recombinant CTRP1 was able to inhibit the increase of blood glucose in diabetic model mice (Rodriguez et al., 2016), and CTRP9 was found to decrease blood glucose levels and insulin resistance in mice (Wong et al., 2009). Furthermore, a study found that the protein expression of CTRP3 was reduced significantly in the hippocampus of depressive mice, subsequently the knockout of CTRP3 induced depressive-like behaviors and triggered inflammation response in mice; the overexpression of CTRP3 can alleviate depressive-like behaviors and exert anti-apoptotic effect (Meng et al., 2019). So far, there are few human researches about CTRPs family.

Human CTRP4 is a member of the CTRPs family (Wang 2017). It was found that CTRP4 is structurally distinct from other members, containing two C1q globular domains and lacking a collagen-like domain (Wang 2017). In addition, CTRP4 can be detected in brain, adipose, blood and bone stem cells, and was highly expressed in the brain. A recent study detected gene expression related to learning and memory in CTRP4-KO mice, and the results showed that the expression of Arc and c-fos was significantly downregulated, while these two genes were proven to play an important role in learning and memory (Sarver et al., 2021). In addition, CTRP4 was confirmed to possess the regulation of glucose and lipid metabolism. Studies indicated that CTRP4 transgenic mice owned higher levels of food intake and were highly resistant to hyperglycemia and obesity (Byerly et al., 2014). The study also found that the group receiving CTRP4 injections decreased food intake and the phenomenon was associated with orexigenic neuropeptide genes in the hypothalamus. The decreased expression of Npy and Agrp genes in the hypothalamus could affect energy intake and metabolism. According to this evidence, it is plausible to suppose that CTRP4 could be an important regulator for brain functions including memory, learning, and metabolism, therefore, CTRP4 might be an effective link between depression and obesity. However, few studies have been performed to examine an association between CTRP4 and different clinical features in a human population sample. Thus, we conducted a case-control study. Since the level of serum CTRP4 could be detected, we decided to measure the serum CTRP4 levels based on MDD patients (the current stage of the disease) and to analyze its underlying clinical implications and practicality as a biomarker in depression.