In this cross-sectional observational study, 40 drug naïve, newly diagnosed patients suffering from depression were recruited. Patients were from Outpatient Department of Psychiatry, King George’s Medical University Hospital, Lucknow, Uttar Pradesh, India. Time period for conducting the study was one year.

Ethical clearance was taken from Ethical committee KGMU before the start of research activity (Ref. code- 97 ECM II B- Thesis/P16, dated: 29/9/2019). Informed written consent was obtained from each patient. All the patients were interviewed by experienced psychiatrists. The patients were divided into two groups {mild depression (F32.0) and severe depression (F32.2)} according to the severity of symptoms based on ICD-10.

Sample size calculation: Sample size was calculated on the basis of proportion of raised CRP level among the population under study using the formula:

Where, p=20.5% (average of 13.7 in males and 27.3% in females) proportion of raised CRP level [10]

q=100-p,

Type I error α=5%, for the significance level of 95%.

Allowable error L=10% absolute for detecting the results with 80% power of study,

The minimum sample size required came out to be n=65.

Forty patients were included due to COVID-19 pandemic. Out of 40 cases, 22 were males and 18 were females.

Inclusion criteria: Age between 18-40 years; irrespective of gender were included. Diagnosis and classification of depressive patients according to severity of symptoms was based on ICD-10 Classification of Mental and Behavioural Disorders [11]. For assessing the severity of depression Hamilton Depression Rating Scale (Ham-D) was used on all patients via a structured interview.

Exclusion criteria: Patients with history of any metabolic syndrome, history of any cardiovascular disease, history of any other psychiatric illness, epilepsy, head injury, alcohol intake and smoking were excluded.

The BP was measured manually by sphygmomanometer. Height and weight of each patient was taken and BMI was calculated by the formula wt (in kgs)/Ht² (in mtrs). Peripheral blood sample of about 2 mL was obtained from each patient by venipuncture and collected in a plain vial between 9 am to 12 noon. Serum was isolated from blood via centrifugation at 3000 rpm for five minutes and stored at -24°C. This procedure was followed till all the samples were collected and then quantification of CRP levels was done at once by Enzyme Linked Immunosorbent Essay (ELISA) method. Serum levels of CRP were measured by commercially available ELISA Kit in Pathology Department (manufactured by Bioassay Technology Laboratory, Korain Biotech Co., Ltd.,).

Statistical analysis was accomplished using SPSS 23 statistical software. Descriptives were stated as the mean±Standard Deviation (SD). Comparison of serum CRP levels between mild depression patients and severe depression patients was done with “unpaired t-test.” A p-value ≤0.05 was considered to be statistically significant.

A total of 40 cases were enrolled in the study, 20 with mild depression and 20 with severe depression. Mild depressive group comprised of 13 males and 7 females with mean age of cases 34.7 years (SD-5.87). Severe depressive group comprised of 9 males and 11 females with mean age of cases 31.9 years (SD-6.36). There was no statistically significant relationship in age and severity of depression (p=0.14). Most of the patients belonged to sedentary type of occupation followed by housewife and few belonged to field work [Table/Fig-1,2 and 3].

Since, the present study focused on comparison of serum CRP levels between mild and severe depression cases, therefore moderate group was not employed in the study. Also, few cases with moderate depression were seen during OPD visits.

On comparing BP in mild depression group to severe depression group, it showed statistically insignificant relationship. For SBP (p=0.102) and for diastolic (p=0.789). When gender based comparison of systolic and diastolic BP were made between mild and severe depression group, statistically insignificant values were obtained [Table/Fig-4 and 5].

On comparing BMI of mild depression group to severe depression group, statistically non significant relationship was seen (p=0.539). Gender specific comparison between BMI and both depression group showed statistically insignificant values, males (p=0.500) and females (p=0.683) [Table/Fig-6].

The mean value of serum CRP in mild depression patient group was 1.23 and in severe depression group was 2.60. Statistically, significant relationship was found between Serum CRP levels and both (mild and severe) depression group (p≤0.015). In males, statistically significant relationship was obtained between serum CRP levels and both (mild and severe) (p=0.027). Similar result was seen in female patients with p=0.04 [Table/Fig-7].

In our country depression is increasing because of stressful lifestyle. WHO also states that 6.5% of Indian population suffers from depression [12]. Increased levels of proinflammatory cytokines are associated with the development of depressive disease [7,8]. Multiple and recurrent episodes of depression are reported to be associated with elevated CRP level [13,14].

In the present study, no significant association was seen between age and severity of depression. In mild depressive patients mean age was 34.75±5.87 years whereas, in the severe depressive patients mean age was 31.90±6.36 years. The probable reason for this might be that elderly people are more receptive to the unavoidable physical illnesses and if they come, they cope up with them strategically. It is demonstrated in the previous studies that major depression is more frequent in young age group than the older one which is consistent with our findings [15].

It was observed that majority of the cases were males as compared to females. The probable reason for increased male to female ratio might be that more number of males attended the OPD and the females were more restricted to household work and did not seek any medical help. Findings of the present study did not match to the previous data available which shows that females are more prone to develop depression at any age group [16,17]. The underlying cause for gender difference in depression might be hormonal and neurodevelopmental changes that vary by sex during the pubertal transition. On the other hand women dedicate themselves to both work and family and thus, they are exposed to a double stress.

Distribution of patients according to their occupation depicted that most of the cases were having a sedentary type of occupation which included teachers, students, shopkeepers. The probable reason for this may be that work constitute an objective source of stress in a person’s life and it could facilitate the occurrence of depressive symptoms. As most of the females are engaged in household work, they have little time for self-reported leisure-time and physical activity. It is demonstrated in previous studies that individuals who have enough time for self-reported leisure-time and practice moderate level of physical activity in their life are less prone to develop depression during their lifetime [18,19].

The mean SBP was found to be 131.80±8.80 mmHg among mild depressive patients whereas among severe depressive patients mean SBP was 126.90±9.68 mmHg. The mean DBP was found to be 82.70±7.18 mmHg among mild depressive patients whereas among severe depressive patients mean DBP was 82.10±6.88 mmHg. According to current findings, there is no significant association between depression severity and BP (including both SBP and DBP). As hypertension is a strong confounding factor for the increase in serum CRP levels, we excluded the patients who were diagnosed with hypertension for minimising the error in our result. George DS et al., conducted a study which showed that hypertension is associated with increased serum CRP levels [20]. He J and Whelton PK and Stamler J et al., concluded that high BP plays an important role as a risk factor in development of cardiovascular disease [21,22]. Study conducted by Barrett-Connor E and Palinkas LA, on elderly population found an inverse relationship between low diastolic BP and depressive symptoms. He also demonstrated that higher levels of depressive symptoms and more diagnosis of depression were found in subjects with DBP <75 mm Hg [23].

The mean BMI was found to be 21.65±1.12 in mild depression patients whereas among severe depressive patients mean BMI was 21.85±0.94. According to present findings, there was no significant association between BMI and depression severity. As it is postulated from previous data that obesity is a strong confounding factor for increase in serum CRP levels, we excluded the patients who were having BMI in range of overweight and obese category. Sample was collected in a resting state after overnight fasting for minimising the error in the results. Both males and females were having nearly equal BMI levels. Previous data shows bidirectional association between depression and obesity [24,25]. The underlying cause for increase of BMI may be neuroendocrine disturbances that occur in patients of depression.

CRP is one of the most broadly researched acute phase reactant. Several studies exhibited increased serum CRP levels in patients suffering from severe depression [26,27]. Valkanova V et al., conducted a meta-analysis which demonstrated a significant association between increased CRP and depressive symptoms [28]. In the present study, however we found statistically significant association between serum CRP levels and severity of depression. This may be explained that depression is multifactorial chronic stress. This leads to altered hypothalamic-pituitary-adrenal axis resulting in dysfunction in immune and endocrine system of the body. These changes may alter inflammatory response. Few previous studies found positive association of raised CRP level when compared to patients with mild and severe depression [29,10]. Previous studies are not consistent with the present findings. Till now, to the best of our knowledge, no study has been found in which CRP levels according to the severity of depression has been studied. Thus, we can prevent landing of mild into the severe form by estimating CRP levels in early phase of depression. We need larger sample size and longer duration study in future to establish negative corelation between CRP levels and severity of depression.

COVID-19 Pandemic was a major limitation of the study. Time period was inadequate for conducting the present study. Larger sample size would have been recruited for obtaining more reliable and accurate results.

It is concluded that severity of depression is negatively associated with CRP levels. Thus, CRP level estimation in early diagnosed cases of depression may be helpful in therapeutic management.