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Acta Medica Mediterranea, 2016, 32: 795 NEUTROPHIL LYMPHOCYTE RATIO IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER SEVDA KORKMAZ1, AFFAN DENK2, BURCU GÜNDOĞAN1, TUBA KORUCU1, ZEHRA EMINE DULKADIR1, SELDA TELO3, MURAD ATMACA1 1 Department of Psychiatry, Fırat University Medicine Faculty, Elazıg, Turkey - 2Department of Infection, Fırat University Medicine Faculty, Elazig, Turkey - 3Department of Biochemistry, Firat University Medicine Faculty, Elazig, Turkey ABSTRACT Introduction: Neutrophil - lymphocyte ratio (NLR) is accepted as an inflammation marker. The objective of the study is to indicate the variations in NLR that occur in patients with major depressive disorder. Materials and methods: Forty prospective patients diagnosed with major depressive disorder based on DSM 4-TR and treated in our clinic were included in the study. The control group included forty healthy individuals that applied to our clinic, however were not diagnosed with active psychopathology in the initial examination, and have matching age and gender demographics with the patient group. Lymphocyte and neutrophil percentages taken during the application before the treatment were recorded in the related forms. NLR was calculated by the division of neutrophil rate by the lymphocyte rate for each patient. Results: There was no significant difference between the groups based on socio-demographic characteristics such as age, gender, marital status, income level, smoking, and employment. Mean NLR value was 1.58±0.59 in the patient group, and it was 2.05±0.89 in the control group. The difference between these mean values was statistically significant (p=0.007). In control group, the neutrophil percentage, and in patient group the lymphocyte percentage was significantly high. There was no difference between the groups on white blood cell count. Conclusion: It was determined that the NLR is significantly lower in patients with major depressive disorder when compared to the control group. The changes in NLR could reflect the changes in central nervous system metabolisms. Thus, NLR could be an indicator of the fact that immune system is suppressed in chronic inflammation in psychiatric diseases such as depressive disorder. Key words: Neutrophil, lymphocyte, major depressive disorder, inflammation. DOI: 10.19193/0393-6384_2016_3_92 Received June 30, 2015; Accepted January 02, 2016 Introduction Acute inflammatory events or bacterial infections increase neutrophil production and inflammatory infiltration. Neutrophils activated by tissue destruction release certain enzymes such as myeloperoxidase, acid phosphatase, and elastase(1). This condition causes changes in the rate of white cells in circulation. Neutrophilia is accompanied with relative lymphopenia. Since this physiological response by white blood cells in circulation against stress results in an increase in the number of neutrophils and a decrease in the number of lympho- cytes, the ratio of these sub-groups (NLR) is considered as an inflammation marker in certain diseases(2, 3). In recent years, NLR is used to measure the severity of the inflammation in various conditions such as cardiovascular diseases(4), malignity(5, 6) , osteoporosis (7), and Behcet’s disease (8). It was argued that it could be used as an inflammatory marker in the examination of psychiatric diseases as well, since variations in lymphocyte rates reflect the changes in central nervous system cell metabolisms(9). Although it is known for long that inflammatory processes could play a role in the pathogenesis of depressive disorder, there are only a few 796 studies in the literature that assessed NLR in this patient population(10). Thus, the objective of this study is to compare NLR in patients with major depressive disorder to those of the healthy control group. Materials and methods The study was initiated after the approval of the local ethics committee according to the Helsinki Declaration. Forty prospective patients with major depressive disorder, who applied at Firat University Hospital Mental Health and Diseases Clinic and did not use any psychiatric drugs during the previous month, were included in the study. Depressive disorder was diagnosed based on Mental Disorders Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) (American Psychiatric Association, 1944)(11). The control group included 40 healthy individuals that applied to our clinic, but not diagnosed with active psychopathology in the examination and have matching age and gender demographics with the patient group. Three venous blood samples taken from antecubital region of all patients during the initial clinical examination before the treatment and placed in hemogram tubes containing K2EDTA (di-potassium, ethylenediamine tetra acetic acid). Advia 2120 equipment (Siemens Healthcare Diagnostics Inc., Tarrytown, New York, USA) was used for full blood count. The study exclusion criteria were: to be under 18 years of age, psychiatric drug use during the previous month, having a known blood disease, history of alcohol or substance use, known diabetes, history of cardiac disease, history of chronic inflammatory or autoimmune disease, history of local or systemic infection in the last month, detection of active infection by Infectious Diseases specialist on physical examination, consumption of over 15 cigarettes daily, and having a body mass index of over 30 (BMI > 30kg/m2). General medical conditions, histories and family histories of the patients and control group, and their socio-demographic data such as age, gender, and education were recorded in forms prepared by the researchers. Furthermore, lymphocyte rate, neutrophil rate, platelet rate, and the calculated NLRs for the patient and control groups were recorded in these forms. Statistical analysis All analyses were conducted using Statistical Package for the Social Sciences 21 software (SPSS Sevda Korkmaz, Affan Denk et Al for Windows 21). Continuous variables were indicated as mean ± standard deviation and the categorical variables were indicated in percentages (%). Chi-square test and Student T-test were used in the comparison of the patient and control group data. P < 0.05 value was accepted as statistically significant for the analyses. Results Statistical analysis identified that there were no significant differences between the depression group and control group based on the socio-demographic characteristics such as age, gender, marital status, income level, smoking and employment (Table 1). Major Depressive Disorder n (%) Control n (%) 43± 12 43± 8 Male 17 (43%) 18 (45%) Female 23 (57%) 22 (55%) Age (years) Gender Marital Status Married 31 (78%) 24 (60%) Bachelor 2 (5%) 14 (35%) Divorced 7 (18%) 2 (5%) Low Income Level 7 (18%) 8 (20%) Smoking 7 (43%) 13 (33%) Unemployed 30 (75%) 18 (45%) Illiterate 7 (18%) 4 (10%) Primary school 21 (52%) 12 (30%) Secondary school 9 (23%) 13 (33%) Education College 3 (8%) 11 (28%) With an organic disease 18 (45%) 17 (43%) Table 1: Comparison of socio-demographic characteristics of the patient and control groups. Mean white blood cell (WBC) count was identified as 6.75±1.75 (x103) in the patient group and as 7.09±1.3(x103) in the control group and there was no statistically significant difference between these groups (p= 0.329). Neutrophil percentage was statistically significantly higher in the control group (56.8±7.67) when compared to the patient group (52.02±8.46) (p=0.009). Lymphocyte ratio was indicated as 35.5±7.3% in the patient group, and as 30.9±7.8% in the control group and there was a statistically significant difference between them (p = Neutrophil lymphocyte ratio in patients with major gepressive disorder 0.008). NLR was found as 1.58± 0.59 in the patient group and as 2.05±0.89 in the control group. The difference between the groups was evaluated as statistically significant (p = 0.007) (Table 2). 797 NLR: neutrophil lymphocyte ratio, *p<0.05 known, all glucocorticoid secretion, and especially cortisol secretion increase due to hyper activation of hypothalamus-pituitary-adrenal axis under stress(16). It was observed in various studies that plasma cortisol concentration and cortisol metabolites were increased and 24-hour urea free cortisol concentrations rose in most patients with major depression(17). It is possible that increasing cortisol hormone and certain hypothalamic changes could have created a decrease in immune response and could have lowered NLR values. Since variations in neutrophil and lymphocyte rates reflect changes in central nervous system cellular metabolisms, they could be utilized as a marker for chronic inflammation in psychiatric diseases related to inflammation such as depressive disorder. However, to prove this view, further studies with a larger sample and using clinical scales that measure the severity of the disease are warranted. Discussion Conclusion This study is the first study in the literature that examined the NLR in patients with major depressive disorder. NLR value was statistically significantly different in the patient group when compared to the control group. Recently, studies that measured the severity of inflammation in schizophrenia patients(12) and patients with bipolar disorder(13) using NLR were published. These studies determined that there was an increase in NLR in patient groups and reported increased inflammation levels in this patient population based on this data. However, the variations in NLR were not clear in the population of depressive patients. In this study, NLR ratio was lower in depressive group compared to the control group. Thus, the finding of this study, which demonstrated lower NLR ratio in patient group, was a striking finding. Studies reported that stress and depression cause negative effects on the immune system and the immune system is suppressed following negative events in life(14). Based on the acute or chronic character of the stress, responses of the organism might differ. It is known that acute and mild stress increase certain immune system functions, whereas chronic and severe stress suppresses the cellular immune system functions(15). It could be possible that in patients that experienced chronic and severe stress such as major depression as demonstrated in this study, cellular immune system could have been suppressed, and thus, lower NLR values could have been observed. As is NLR is a parameter, which provides immediate results with a minimum cost and could be utilized as an auxiliary to the known inflammatory indicators used in several diseases dominated by systemic inflammation. We consider that further studies would better demonstrate the relationship between NLR and the severity and activation of major depressive disorders. Major Depressive (n:40) Control (n:40) Hemoglobin (g/dL) 13.06± 1.88 14.4±1.43 0.001* Hematocrit (%) 38.9± 5.1 43.7±4.5 <0.001* WBC (x103) 6.75± 1.75 7.09±1.3 0.329 RBC (10 /mL) 4.54± 0.46 4.99±0.55 <0.001* Platelet (10 /L) 265.6± 79.3 271.5±51.9 0.694 6 9 p Neutrophil (%) 52.02± 8.46 56.8±7.67 0.009* Lymphocyte (%) 35.5± 7.3 30.9±7.8 0.008* NLR 1.58± 0.59 2.05±0.89 0.007* Table 2: Comparison of hematologic parameters of the patient and control groups. Limitations The limitations of the study are the low number of cases scrutinized, and the lack of comparison with other inflammation markers. References 1) 2) 3) Reichlin T, Socrates T, Egli P, Potocki M, Breidthardt T, Arenja N at al. Use of myeloperoxidase for risk stratification in acute heart failure. Clin Chem 2010; 56: 944-51. 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J Psychiatry1996; 168 (30): 123- 8. _______ Corresponding author SEVDA KORKMAZ, MD Department of Psychiatry, Fırat University Medicine Faculty, Elazig (Turkey)