Cystatin C and risk of new-onset depressive symptoms among individuals with a normal creatinine-based estimated glomerular filtration rate: A prospective cohort study

Li, Haibin; Wang, Anxin; Gao, Qi; Guo, Jin; Li, Xia; Wang, Wei; Xiang, Yu Tao; Guo, Xiuhua

doi:10.1016/j.psychres.2019.01.009

Cited by 9 publications

(11 citation statements)

References 50 publications

(66 reference statements)

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“…This enzyme has been proposed as a biomarker of renal insufficiency and it has been shown to correlate with depressive symptoms in the elderly with normal renal function ( Minev et al, 2010 ). Accordingly, a greater Cys-C levels were associated with an increased risk of new diagnosis of depression in subjects with normal renal function ( Li H. et al, 2019 ). Furthermore, cognitive decline and AD are associated with renal impairment in human ( Zhang et al, 2020 ) and in animal model of AD ( Nakagawa et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Depressive symptoms have also been associated with increased peripheral levels of Cystatin-C (Cys-C), a low-molecular-weight protein, synthesized at a constant rate in all nucleated cells ( Li H. et al, 2019 ; Huang et al, 2021 ). Cys-C has been thought to be crucially implicated in the development of soluble Aβ neuronal dysfunctions, also relating to cognitive impairment ( Zeng et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

et al. 2022

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Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

et al. 2022

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“…Several studies have examined a potential link between Cys C levels and depression [ 29 , 30 , 41 ]. A study that enrolled 1440 Chinese older adults (> 60 years old) found a detrimental relationship between high serum Cys C levels and the risk of depression [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…A study that enrolled 1440 Chinese older adults (> 60 years old) found a detrimental relationship between high serum Cys C levels and the risk of depression [ 29 ]. Another prospective cohort study of 11,847 Chinese people (> 45 years old) by Li H et al [ 41 ] showed that high levels of Cys C were associated with an increased risk of depression. They calculated the risk of depression using a corrected Poission regression model and found that the association between serum Cys C and the risk of depression remained significant after adjustment for multiple covariance.…”

Section: Discussionmentioning

confidence: 99%

Associations of serum cystatin C with depressive symptoms and suicidal ideation in major depressive disorder

Sun

Chen

2021

BMC Psychiatry

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Background Individuals with major depressive disorder (MDD) have high suicidal ideation. There is evidence that serum cystatin C (Cys C) may be involved in the pathophysiology of MDD. The present study aimed to investigate Cys C concentration in patients with MDD and clarify its possible association with depressive symptoms and suicidal ideation. Methods An online cross-sectional survey of 159 patients diagnosed with MDD was conducted. Serum Cys C levels were measured using ADVIA 2400 biochemical analyzer. The 24-item Hamilton Depression Scale (HAMD-24) was administered to evaluate the depressive symptoms. Generalized linear regression, logistic regression and restricted cubic spline models were used to examine the association of serum Cys C levels with depressive symptoms and suicidal ideation. Results Serum Cys C levels were higher in MDD patients than in controls (p = 0.001) and were positively associated with scores on HAMD-24 in unadjusted (gender distribution, age, smoking, alcohol consumption, family history of depression and traumatic life events; (p = 0.003) and fully adjusted linear regression model (p = 0.005). The fully adjusted regression coefficient with 95% confidence intervals for serum Cys C levels and HAMD-24 score was 30.339 (9.602 to 51.077). The level of Cys C in the suicidal ideation (SI) group was significantly higher than that in the non-suicide ideation (non-SI) group (p = 0.001). Serum Cys C levels were positively associated with suicidal ideation in each logistic regression model (all p < 0.05). Conclusion Serum Cys C levels were elevated in MDD patients and appeared to be positively correlated with depressive symptoms and suicidal ideation. These findings suggest that the dysfunction of Cys C may be involved in the severity of depression and in the pathophysiological process of MDD. Thus, regulation of serum Cys C could potentially be an effective predictor of the severity of depression and potentially, play a role in reducing the risk of suicide in MDD patients.

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“…Several researchers have already evaluated the potential link between cystatin C levels and depression (38)(39)(40). A study which enrolled 1,440 Chinese elders (>60 years old) found a harmful relationship between high serum cystatin C levels and risk of depression (38).…”

Section: Discussionmentioning

confidence: 99%

Persistent Depressive Symptoms and the Changes in Serum Cystatin C Levels in the Elderly: A Longitudinal Cohort Study

Han

Zhang²,

Jiang³

et al. 2022

Front. Psychiatry

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BackgroundThe burden of depression in the elderly is increasing worldwide with global aging. However, there is still a lack of research on the relationship between depressive symptoms and the progression of renal function. Our aim is to evaluate the longitudinal association between baseline depressive symptoms and the changes in serum cystatin C levels over 10 years' follow-up period.MethodsWe used longitudinal data from the Health and Retirement Study (HRS), an existing community based nationally representative aging cohort study which enrolled individuals over age 50 in the USA. Depressive symptoms were determined using an eight-item version of the Center for Epidemiologic Studies Depression Scale (CESD) at wave 7 (2004) and wave 8 (2006). Persistent depressive symptoms were defined as both CESD scores measured at waves 7 and 8 were ≥3; episodic depressive symptoms were defined as CESD scores ≥3 at wave 7 or wave 8. A linear mixed model was used to evaluate the correlation between baseline depressive symptoms and future changes in cystatin C levels.ResultsThe mean age of the 7,642 participants was 63.8 ± 10.8 years, and 60.9% were women. Among the participants, 1,240 (16.2%) had episodic depressive symptoms and 778 (10.2%) had persistent depressive symptoms. Compared with participants with no depressive symptoms at both waves, a significant increase in serum cystatin C levels was found among those with persistent depressive symptoms.ConclusionsOur results showed that baseline persistent depressive symptoms were significantly associated with an increased rate of serum cystatin C levels. The level of serum cystatin C should be monitored in the elderly with persistent depressive symptoms.

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Cystatin C and risk of new-onset depressive symptoms among individuals with a normal creatinine-based estimated glomerular filtration rate: A prospective cohort study

Cited by 9 publications

References 50 publications

Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

Associations of serum cystatin C with depressive symptoms and suicidal ideation in major depressive disorder

Persistent Depressive Symptoms and the Changes in Serum Cystatin C Levels in the Elderly: A Longitudinal Cohort Study

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