ABSTRACT

Corresponding Author:
Dr. Anindya Dasgupta,
Professor & HOD,
Department of Biochemistry,
Calcutta National Medical College,
Kolkata-700014, West Bengal, India.
E-mail: anindya653@gmail.com

ABSTRACT

BACKGROUND

Studies indicate that along with many other factors, low grade inflammation may play an important contributory role in the development of major depressive psychosis. This may add up as a confounding factor for different complications related to this major psychological disorder. The role of hsCRP as a marker of low grade inflammation has been explored and analysed in the present study.

METHODS

HsCRP, Total Cholesterol (TC), Triglyceride (TG) and Fasting Blood Glucose (FBG) were measured in 49 cases of major depression against 40 age and body weight (BMI) matched control subjects. The degree of depression in the case group was assessed by the HAM-D score. Data were analysed for any differences in these parameters between the case and control groups followed by correlation and regression analysis to assess the strength of association between the study parameters and the predictive values of serum cholesterol, triglyceride, FBG and HAM-D score on hsCRP.

RESULTS

HsCRP, TC and TG were significantly higher in the case group. The correlation and regression analyses revealed that hsCRP was strongly associated (r=0.559, P <0.001) and dependent (beta=0.579, P <0.001) on the HAM-D score only.

CONCLUSION

These results not only indicate a definite association of low grade inflammation with major depressive psychosis, but also suggest a close linear relationship between this low grade inflammation and the degree of depression. The researchers propose that hsCRP is a good indicator for monitoring the pro-inflammatory status and the degree of severity of the disease process in major depressive psychosis.

KEYWORDS

HAM-D Score, hsCRP, Low Grade Inflammation, Major Depressive Psychosis.

INTRODUCTION

In terms of its prevalence and sufferings, depression is a disorder of major public health importance along with the huge economic burden for the individual and the society overall. In India, prevalence of depression in community varies from 1.7 to 7.4 per thousand population.^[1] Pathogenesis of depression is not fully understood, but studies suggest that among many other precipitating factors low grade systemic inflammation plays an important contributory role in the development of depression.^[2] A few studies have suggested that depression may be associated with increased production of pro-inflammatory cytokines such as IL-1, IL-6 and interferon.

Level of sig. P <0.05 at 95% CI.

*P-value significant at 0.05 level.

Bivariate Pearson’s correlation study, however, suggested a strong association between the hsCRP and degree of depression only (Table 3, Figure 1).

X₁ = HAMD score, X₂ = Serum hsCRP (mg/dL), X₃ = Serum Total Cholesterol (mg/dL), X₄ = Serum triglyceride (mg/dL), X₅ = Plasma FBG (mg/dL)

Level of sig. P <0.05 at 95% CI *P-value significant at 0.05 level.

Fig. 1: Scatter Plot showing Positive Bivariate Correlation (r=0.559; P <0.05) between Serum hsCRP (mg/dL) and HAMD Score in the Case Subjects (N=50)

Based on this finding, multiple linear regression was performed considering hsCRP as the only dependent variable and serum cholesterol, serum triglyceride, FBG and HAM-D score as independent variables taken together. It was found that hsCRP had significant dependence only on the HAM-D score (β=0.735, t=6.286. P <0.001) (Table 4).

Level of sig. P <0.05 at 95% CI.

*P-value significant at 0.05 level.

Precision of the tests was monitored assessing the coefficient of variation (CV). CV for the FBG, serum cholesterol and triglyceride remained under 9 percent, while that for the hsCRP was below 6 percent on average throughout the study period.

DISCUSSION

For nearly two decades, it has been recognized that immune system plays a major role in depression. Role of systemic immune activation has been documented in major depression with respect to changes in acute phase response, notably enhancement of positive and diminution of negative acute phase proteins that mark the systemic inflammation.^[3-9] CRP is an acute phase protein that suggests the systemic inflammation. This study, however, stems from the research question whether systemic inflammation precedes the onset of depressive symptoms or occurs as a part of somatic manifestation of the depressive phenotype. Although the CRP level is traditionally only elevated in severe inflammation, newer assays with improved sensitivity are able to measure hsCRP in apparently healthy individuals, permitting an exploration of the postulated association between subclinical systemic inflammation and risk of depression.

Inferential statistical calculation considering both parametric and non-parametric distribution of data in the present study showed that serum hsCRP level was significantly higher in newly diagnosed depressive cases than those of healthy controls (Table 1 and 2). In a recent study it was reported that elevated CRP levels were associated with an increased risk of psychological distress and depression. This association was observed in 73131 individuals in a cross sectional analyses and in prospective analyses for hospitalization with depression.^[12] Although previous studies have corroborated the association of elevated CRP levels with psychological distress and depression, the results were conflicting and varied according to differential distribution of race, region or gender.^[4,7,8] A significant positive association between the Centre for Epidemiologic Studies Depression Scale (CES-D) and hsCRP levels among African-American men with depression was found that was absent in their female counterparts.^[13] However, no such gender based variations regarding the association of hsCRP with depression was observed in the present study.

Some earlier studies have shown the probable mechanism of CRP rise in depression. Depression might promote an inflammatory response by activating immune response.^[14] A higher transcription of both Chemokine Ligands (CCL24) as well as Chemokine Receptors (CCR6) have been reported recently in major depressive disorders.^[15] These chemokines are found to attract increasing numbers of T cells and eosinophils.^[16,17], whereas their receptors potentiate the immunological functions of macrophages, B cells and helper T cells.^[18] Alternatively, the effects of depression on inflammation might be due to its link to psychological stress. For a long time, depressive illness is known to be associated with an increase in several phases of psychological stress as evident by various biochemical tests including the cortisol response test to psychological stressors.^[19-22] The latter has also been associated with excessive production of interleukin-6 (IL-6). IL-6 is also the main pro-inflammatory cytokine inducing the synthesis of Type I acute phase protein such as CRP. Also psychological stress has been shown to increase oxidative stress, which in turn through modified lipids and lipoproteins is thought to initiate an inflammatory response in arterial wall.^[8,9] It is recognized that depressive symptoms are associated with enhanced stress-induced norepinephrine responses and norepinephrine dysregulation.^[23] Preliminary evidence suggests that nor-epinephrine dependent adrenergic stimulation results in activation of nuclear factor κβ (NF-κβ), a transcription factor known to promote IL-6 gene expression.^[24] Severity of the depressive symptoms, anger and hostility, alone and in combination is associated with increased gene expression of pro-inflammatory cytokines and chemokines.^[25-27] and elevated levels of IL-6.^[28] Thus, individuals who show elevated levels of stress may respond to daily life stressors with excessive stress induced sympathetic activation that triggers an NF-κβ-dependent cascade of pro-inflammatory events that contribute to increase in        hsCRP.^[29,30]

CONCLUSION

Thus, the present study strongly suggests that the depressive illness is closely linked to a pro-inflammatory condition and therefore heralds an early onset of all such related complications like premature atherosclerosis, cardiovascular disorders and cerebrovascular accidents.

RECOMMENDATION

The present study, hence, suggests a close monitoring and surveillance of all depressive patients for pro-inflammatory markers, particularly the hsCRP to enable an early intervention for preventing low grade inflammation related disorders and atherosclerotic diseases in these patients.

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