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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.
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Corresponding author
SEVDA KORKMAZ, MD
Department of Psychiatry,
Fırat University Medicine Faculty, Elazig
(Turkey)