Nordic Journal of Psychiatry

ISSN: 0803-9488 (Print) 1502-4725 (Online) Journal homepage: http://www.tandfonline.com/loi/ipsc20

The connections among suicidal behavior, lipid

profile and low-grade inflammation in patients
with major depressive disorder: a specific
relationship with the neutrophil-to-lymphocyte
ratio

Okan Ekinci & Asli Ekinci

To cite this article: Okan Ekinci & Asli Ekinci (2017): The connections among suicidal
behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a
specific relationship with the neutrophil-to-lymphocyte ratio, Nordic Journal of Psychiatry, DOI:
10.1080/08039488.2017.1363285

To link to this article: http://dx.doi.org/10.1080/08039488.2017.1363285

Published online: 11 Aug 2017.

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Download by: [Australian Catholic University] Date: 12 August 2017, At: 01:58
 NORDIC JOURNAL OF PSYCHIATRY, 2017
https://doi.org/10.1080/08039488.2017.1363285

ORIGINAL ARTICLE

The connections among suicidal behavior, lipid profile and low-grade

inflammation in patients with major depressive disorder: a specific
relationship with the neutrophil-to-lymphocyte ratio
Okan Ekinci and Asli Ekinci
Department of Psychiatry, Usak University Medical Faculty, Education and Training Hospital, Usak, Turkey

ABSTRACT ARTICLE HISTORY

Objectives: The role of inflammation and lipid metabolism in the pathophysiology of suicidal behavior Received 10 March 2017
has received particular attention in recent years. The neutrophil-to-lymphocyte ratio (NLR) has been Revised 27 July 2017
suggested as a new and more reliable indicator of low-grade inflammation. NLR has been found to be Accepted 30 July 2017
Downloaded by [Australian Catholic University] at 01:58 12 August 2017

altered in major depressive disorder (MDD) and has been related to various factors, including chronic
stress and impulsivity that were previously reported to be related to suicidal behavior. We aimed to KEYWORDS
explore the roles of NLR, C-reactive protein (CRP) and serum lipid levels on suicidal behavior in patients Neutrophil–to-lymphocyte
with MDD. ratio; depression; C reactive
Methods: The study group consisted of 139 inpatients diagnosed with MDD [37 suicide attempters protein; lipid
(SA); 102 suicide non-attempters (NSA)], 50 healthy controls and matched according to age, gender
and education. NLR, PLR, CRP and lipid values were obtained from digital inpatient records.
Results: CRP levels and NLR were substantially higher in patients with SA than in subjects with NSA
and healthy comparison subjects after adjusting the confounding factors. The logistic regression
included two predictive variables for suicide status in patients with depressive disorder (A) previous
suicidal history; (B) NLR.
Conclusions: This is the first study suggesting that NLR may be a trait marker for suicidal vulnerability
via a relationship between NLR and a recent suicide attempt in depressed inpatients. Future prospect-
ive studies are needed to determine the exact roles of NLR, and other inflammatory markers on suici-
dality in MDD.

Introduction attention in recent years. Furthermore, various immune alter-

Suicide is a major and complicated problem in patients with
major depressive disorder (MDD), and its multifaceted nature
makes the management and treatment of these patients dif-
ficult. Previous studies have examined potential biological
markers of suicidal behavior in the context of mood disor-
ders, especially MDD [1,2]. Although research in this area has
been inconclusive, dysfunctions of the serotoninergic system
and the hypothalamic–pituitary–adrenal (HPA) axis have been
reported to be closely related to suicide in subjects with
mood disorders. Furthermore, other neurotransmitters and
neurotrophic factors have been reported to be associated
with suicidal behavior [2,3]. Recently, serum lipid levels have
been suggested to be associated with suicidality in depres-
sive patients. Various studies have investigated a possible
connection between low serum total cholesterol (TC), trigly-
ceride (TG) levels and suicidal behavior [4,5]. However, some
studies have shown no relationship between suicide and lipid
parameters [6,7]. Nonetheless, there is still no clear explan-
ation of the pathophysiology of suicidal behavior in depres-
sive disorders.
The role of inflammation and the immune system in the
pathophysiology of suicidal behavior has received particular
ations, such as abnormal levels of inflammatory cytokines,
have been proposed as potential predictors of which patients
with mood disorders will be suicide attempters and non-
attempters [8,9]. Moreover, various studies have reported
increased cytokine levels in the brain regions previously
implicated in the pathophysiology of suicidal behavior
[10,11]. Possible mechanisms for the effects of inflammation
on suicidality include peripheral inflammatory cytokine access
to the central nervous system (CNS) via the blood-brain bar-
rier (BBB). In addition, inflammatory cytokines in the CNS can
affect monoamine neurotransmission and neuroplasticity
[12–14].
Due to the short half-life of cytokines, C-reactive protein
(CRP) is a relevant alternative for research because of its long
half-life and detectability at lower levels. For many decades,
it has been considered a marker of inflammation. It is an
acute-phase inflammatory protein synthesized by hepatic
Kupffer cells signaling other body cells for destruction by the
complement system and generated in response to increases
in serum IL-6 [15,16]. Few studies have assessed CRP levels in
patients with suicidality, with contradictory results [17,18].
The neutrophil-to-lymphocyte ratio (NLR) has been sug-
gested as a new indicator of low-grade inflammation and a

CONTACT Okan Ekinci drokanekinci@yahoo.com Department of Psychiatry, Usak University Medical Faculty, Education and Training Hospital, Usak, Turkey
ß 2017 The Nordic Psychiatric Association
 2 O. EKINCI AND A. EKINCI
predictor of clinical outcomes in neuroimmune disorders
[19,20]. The NLR can be derived from the white blood cell
count, and it is inexpensive and replicable. More importantly,
it is the ratio of counts of products of two different immune
pathways. Since the NLR mirrors both immune pathways and
may be less changed by unknown factors, it may be more
informative of inflammation than other leukocyte parameters
or other widely used markers, such as CRP [21–23]. CRP has
been shown to induce the synthesis of IL-1a, IL-1b, tumor
necrosis factor- alpha (TNF-a). CRP may also directly promote
monocyte activation by stimulating the release of cytokines,
such as IL-1b, IL-6, and TNF-a [24]. These cytokines involved
in inflammation process may induce neutrophilia and lym-
phopenia. Supporting these findings, NLR has been found to
be significantly correlated with CRP in healthy population
[25–27]. However, some studies have reported that the plate-
let-to-lymphocyte ratio (PLR) may be better than the NLR for
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determining the severity of inflammation [28]. In a limited
number of studies, both NLR and PLR were found to be
closely related to some clinical variables in patients with
MDD [29,30].
As mentioned above, suicide has different biological sup-
ports. Therefore, the introduction of new objective measures
of suicide risk could help to predict which at-risk patients will
attempt suicide. However, it is still difficult to identify easily
accessible biological predictors of suicidal behavior. Although
NLR and PLR could be valuable and simple markers of sui-
cidal behaviors in MDD that could help predict which depres-
sive patients will attempt suicide and reveal the connection
between low-grade inflammation and suicidal behavior, these
markers have never been explored as predictors of suicidal
behavior in patients with MDD. Moreover, no study has
examined NLR and PLR concomitantly with CRP levels, lipid
profiles and other confounding factors in relation to suicidal
behavior in depressive disorder. Therefore, we aimed to
explore the roles of NLR, PLR, CRP and serum lipid levels on
suicidal behavior in patients with MDD, adjusting for poten-
tial confounding factors.
Method
The study was conducted at the Usak University Faculty of
Medicine Psychiatry Clinic. In total, 139 hospitalized patients
and 50 healthy controls who visited the health committee for
a work entrance examination were included in the study. All
patients diagnosed with MDD according to the Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition
(DSM-IV), diagnostic criteria were included in the study [31].
The inclusion criteria were as follows: (1) older than 18 years
of age and (2) diagnosed with MDD according DSM-IV diag-
nostic criteria. The exclusion criteria were as follows: (1) hav-
ing an acute and chronic medical disease; (2) receiving anti-
inflammatory, statin and/or immunosuppressive therapy; (3)
obesity (BMI >30); and (4) dementia or cognitive deterior-
ation according to DSM-IV criteria and the Mini-Mental State
Examination (score >24). All the patients underwent com-
plete blood and urine testing, electrocardiography and
screening for acute infection based on a complete physical
examination, erythrocyte sedimentation rate, complete blood
count, hepatic enzymes and electrolytes. Only patients with
normal ranges of the above-mentioned parameters were
included in the study. In addition, patients with a history of
alcohol or drug dependence or traumatic head injury, any
past or present major medical or neurological illness, and a
current axis I comorbidity and/or comorbid personality diag-
nosis were excluded. The exclusion criteria and the age range
for the controls were identical to those of the patient group.
From the initial sample of 202 patients, 32 were excluded
because they were diagnosed with a current axis I disorder
comorbidity and/or a comorbid axis II disorder; two were
excluded due to cognitive deterioration; two were excluded
because of mental retardation; and 13 were excluded
because they had comorbid substance abuse. Ten patients
were excluded because they had acute or chronic medical
diseases. Finally, four patients were excluded due to the
absence of levels of lipid and markers of inflammation in
their records. Thus, 139 consecutive inpatients were included
in the final sample. Among the 139 patients, 37 (26.6%) were
admitted for a suicide attempt within the past 15 days. The
patients with a recent suicide attempt were medically stable
because they were admitted to our clinic after hospitalization
at an internal medicine clinic for medical follow-up and sta-
bilization. Suicide attempt was defined as a self-damaging
act carried out with some intent to die, as distinguished from
other self-destructive behaviors, such as self-mutilation. No
subjects received either antidepressants or anxiolytics at the
time of sample collection. However, most of the patients
were taking regularly either an antidepressant or an anxio-
lytic medication prior to the hospitalization.
The subjects with MDD were recruited from among
patients hospitalized at the inpatient unit of Usak University
Hospital. The study was reviewed and approved by our insti-
tutional review board. Clinical variables were collected
through a psychiatric interview and a review of the digital
patient charts and inpatient files. Data were retrieved from
the electronic medical records of all patients between May
2016 and Jan 2017 at Usak University Hospital. At admission,
the severity of the patients’ mood symptoms was routinely
assessed with the Hamilton Depression Rating Scale (HDRS)
[32,33]. The study utilized a retrospective, cross-sectional
study of patients’ records to obtain complete blood count,
lipid and CRP levels. All parameters were determined in the
inpatient psychiatry clinics as part of the routine laboratory
tests conducted upon admission. At our clinic, fasting blood
samples were collected between 7:00 and 8:00 AM. Weight
and height were measured to calculate the body mass index
(BMI). The following parameters were reviewed for all the
subjects: high-density lipoprotein cholesterol (HDL), low-
density lipoprotein cholesterol (LDL), total cholesterol (TC),
triglyceridemia (TG), C-reactive protein (CRP), and complete
blood count. The NLR was calculated by dividing the abso-
lute neutrophil count by the absolute lymphocyte count. The
PLR was calculated by dividing the platelet count by the
absolute lymphocyte count. For the serum lipid concentra-
tion, enzymatic methods were used, and serum levels of CRP
were determined using sensitive regular immunoassays
(ELISA) that allow the detection of a minimal CRP

concentration of 0.1 mg/dL. All CRP levels were below 11 mg/
dL, which reduced the chance that an acute physical illness
was the cause of the inflammatory state. In the present
study, we have taken into account some demographic varia-
bles as confounding factors because of the previous studies
which reported a relation to inflammation and lipid markers.
Current evidence suggests that socioeconomic status
whether indicated by education [34]; composites of income
[35] is inversely related to CRP. In addition, social and eco-
nomical deprivation assessed by place of residence is associ-
ated with low-grade inflammation indicating an increase in
CRP levels [36]. The level of education and socioeconomic
status have also been shown to be related to the levels of
lipid parameters in men and women [37].
Statistics
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We used SPSS for Windows 16.0 (Chicago, IL) for all the stat-
istical analyses in this study. A confidence interval of 95%
and a two-tailed p value less than 0.05 were considered stat-
istically significant for all analyses. The variables were tested
for homogeneity of variance using the Levene test and for
the normality of distribution using the Kolmogorov–Smirnov
test. Data that departed significantly from normal distribution
or homogeneity of variance were analyzed nonparametrically.
To compare the sociodemographic characteristics of patients
and controls, the chi-squared test was used. Pearson’s correl-
ation was performed to analyze the correlation coefficients
for lipid levels and markers of inflammation. To determine
the factors associated with suicide attempt, the first statistical
analysis was performed using one-way analysis of variance
with the post-hoc Tukey test and the t-test for independent
samples. A risk factor model was created using these results,
and these variables were used for the secondary analysis.
The secondary analysis involved a multivariate linear regres-
sion analysis of covariance. Age, BMI, HAM-D scores, and
years of education were the continuous variables; sex, suicide
attempt, and smoking were the dichotomous categorical pre-
dictor variables; and lipid levels and markers of inflammation
were the dependent variables.
Potential predictors of suicide attempt were selected
based on a review of other studies of the association
between suicide, lipid levels and inflammation variables. All
variables were evaluated for skewness and univariate outliers
to determine the appropriate statistical approach. The associ-
ation between these variables and suicide were first exam-
ined in a series of bivariate analyzes. Then, all of the
predictors of interest were entered into a logistic regression
with suicide attempt as the dependent variable. We utilized a
forward stepwise regression to identify significant predictors
of suicide to avoid the risk of collinearity. The likelihood-ratio
chi-square difference (LR) was used to select the best model.
We report associations between variables as odds ratios (OR)
and their 95% confidence intervals (95% CI).
Results
A total of 139 patients with MDD (97 women and 42 men) and
50 healthy controls (37 women and 13 men) were included in
NORDIC JOURNAL OF PSYCHIATRY 3
the study. The patients were categorized into two groups
according to suicide attempts. Among the patients, 37 (26.6%)
had recently attempted suicide [suicide attempters (SA) vs.
non-suicide attempters (NSA)]. The most common method of
suicide attempt was drug overdose [28], followed by wrist/
neck cutting [6], hanging [2], and stabbing self in the abdomen
[1]. The mean age was 43.00 ± 14.15 years for the SA group,
41.88 ± 11.49 years for the NSA group and 44.12 ± 4.23 for the
control group (mean ± s.d). The three groups were compared
in terms of age, sex, education, socioeconomic class, place of
residence, BMI, previous suicide attempt and smoking status.
As shown in Table 1, the patients and controls did not differ
significantly in any of these features except previous suicide
attempt. The SA group had a significantly higher rate of previ-
ous suicide history than the NSA group (v2 ¼ 92.37, df ¼1,
p < .001).
Regarding the markers of inflammation, the CRP levels
and the NLR were substantially higher for the SA group
than the NSA and healthy comparison groups, as shown in
Table 2 (F ¼ 2.77, p < .018 and F ¼ 32.75, p < .001). When
examining CRP as a categorical measure [high CRP (3) vs.
normal CRP (<3)], we did not find any significant differen-
ces in the CRP subgroups of suicidal and nonsuicidal
patients (v2 ¼ 0.416, p ¼ .326). However, the NSA group had
significantly higher TC levels than the SA (F ¼ 5.46;
p ¼ .021). Table 3 shows the correlation coefficients of the
variables related to the lipid profile and inflammation
markers in the patients with MDD.
We next investigated the role of education, age, BMI, smok-
ing status and sex in these differences. We conducted general
linear model analyses with age, HAM-D scores, BMI and educa-
tion as continuous predictors; sex, smoking and recent suicide
attempt as categorical predictors; and lipid and inflammation
parameters as dependent variables. After these factors were
adjusted, the suicidal patients still had significantly higher CRP
levels and NLRs than the nonsuicidal patients. However, the
difference in TC levels between patients with NSA and SA did
not remain significant after controlling for these covariates
(F ¼ 2.926, p ¼ .09). Gender alone did not significantly contrib-
ute to any parameters. However, the interaction between gen-
der and suicide significantly contributed to LDL and TC levels
(F ¼ 5.687, p < .001). Female participants in the NSA group had
significantly higher LDL levels than the female patients in the
SA group and the male patients in the NSA group (F ¼ 26.44;
p < .001; 116.54 ± 36.4 vs. 80.73 ± 19.56 and 85.77 ± 36.54,
respectively). Regarding TC levels, female patients in the NSA
group had significantly higher TC levels than their female
counterparts in the SA group and the male subjects in the SA
and NSA groups (F ¼ 16.25, p < .001).
A binary logistic regression with recent suicide attempt
(SA vs. NSA) as a dependent variable was applied. The model
included age, education, sex, BMI, smoking status, previous
suicide attempt, lipid levels, socioeconomic level, place of
residence, BMI, CRP levels, and PLR and NLR as independent
variables. The logistic regression model was statistically sig-
nificant (v2 (2) ¼ 127.22; p < .001). The logistic regression
equation correctly classified 78.4% of the suicide cases.
The logistic regression included two predictive variables for
suicide status in patients with depressive disorder.
 4 O. EKINCI AND A. EKINCI

Table 1. Clinical and demographic features of controls and patients with and without suicide attempt.
Patients with recent Patients without
suicide attempt recent suicide Healthy controls
N ¼ 37 attempt N ¼ 102 N ¼ 50
Mean SD Mean SD Mean SD Statistic p Value
Age 43.00 14.15 41.88 11.49 44.12 4.23 F ¼ 3.77 0.121
Years of education 7.37 2.41 7.55 2.08 7.23 3.45 F ¼ 2.3 0.110
BMI 25.08 0.71 26.34 1.12 25.39 1.83 F ¼ 1.33 0.105
HAM-D 33.12 1.31 27.54 1.12 3.13 1.05 F ¼ 6.23 0.001
n % n % n %
Gender
Female 22 77.3 75 64.3 37 74 v2 ¼ 2.55 0.143
Male 15 22.7 27 35.7 13 26 df ¼ 1
Marital status
Single 14 40 21 60 10 20 v2 ¼ 4.29 0.059
Married 23 22.1 81 77.9 40 80 df ¼ 1
Previous suicide attempt
No 10 8.9 98 96.1 45 100 v2 ¼ 92.37 <0.001
Yes 27 91.8 4 3.9 0 0 df ¼ 1
Socioeconomic status
Low 2 40 3 60 1 2 v2 ¼ 3.29 0.193
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Medium 34 25 99 74 46 92 df ¼ 2
High 1 100 0 0 3 6
Place of residence
Rural 10 23 33 77 16 32 v2 ¼ 3.72 0.155
Urban 27 28 69 72 34 68 df ¼ 2
Smoking status
No 24 29 57 71 29 58 v2 ¼ 0.901 0.437
Yes 13 23 45 77 21 42 df ¼ 1
HAM-D: Hamilton Depression Rating Scale; BMI: Body Mass Index; SD: standard deviation of mean.
p < 0.05.
p < 0.001.

Table 2. Comparison of laboratory parameters between patients with and without recent suicide attempt at admission.
Patients with recent Patients without
suicide attempt recent suicide Healthy controls
N ¼ 37 attempt N ¼ 102 N ¼ 50
Mean SD Mean SD Mean SD Statistic p Value Post-hoc analysis
LDL 94.622 6.138 108.374 3.697 95.22 7.128 F ¼ 3.683 .057
TG 152.297 12.869 130.559 7.751 127.59 11.34 F ¼ 2.094 .150
Total Cholesterol 159.919 73.08 179.853 44.02 179.23 47.11 F ¼ 5.460 .021 HC ¼ NSA > SA
HDL 42.765 1.506 44.494 0.907 46.21 1.83 F ¼ 0.968 .327
CRP 2.651 0.382 1.909 0.230 1.68 0.68 F ¼ 2.771 .018 SA > NSA > HC
Platelet counts 232,890 58,705 250,760 67,624 225,219 57,312 F ¼ 2.028 .157
NLR 2.840 0.162 1.858 0.98 1.81 0.33 F ¼ 32.757 <.001 SA > NSA > HC
PLR 141.4 83.25 128.11 48.76 134.3 61.4 F ¼ 1.348 .248
N (%) N (%) N (%) v2 ¼ 0.416 .327
CRP status Normal 24 28 61 72 30 60 df ¼ 1
High e13 24 42 76 20 40
LDL: low-density lipoproteins; TG: triglycerides; HDL: high-density lipoproteins; NLR: neutrophil to lymphocyte ratio; PLR: platelet to lymhocite ratio; CRP: c-reactive
protein; SD: standard deviation of mean; HC: healthy controls; SA: Patients with recent suicide attempt; NSA: Patients without recent suicide attempt.
p < 0.05.
p < 0.001.

Table 3. Correlation coefficients of variables related to lipid profile and inflam-

mation markers in patients with MDD. Discussion
LDL TG TC HDL CRP NLR To the best of our knowledge, this is the first study to exam-
TG 0.341 ine the role of the NLR and PLR together with lipid values,
TC 0.952 0.452
HDL 0.296 0.138 0.387 CRP and other predictive factors in suicidality in MDD. The
CRP 0.078 0.268 0.105 0.259 present study mainly suggested that the NLR and a prior sui-
NLR 0.203 0.150 0.125 0.336 0.003 cide attempt were significantly related to recent suicide
PLR 0.130 0.188 0.086 0.232 0.111 0.419
p < 0.05.
attempts in patients with MDD. In addition, the CRP and TC
p < 0.001. levels did not predict suicide attempts, although the two var-
iables differed significantly between the patients with and
without a recent suicide attempt.
These variables were (A) previous suicide history (b ¼ 5.06;
In the present study, the suicidal depressive patients had
Exp b ¼ 0.006%95 C.I.¼ 0.001 – 0.098; p < .001) and (B) NLR
higher NLRs than both the nonsuicidal patients and the
(b ¼ 2.322, Exp b ¼ 3.46%95 C.I.¼ 1.962 – 6.102; p < .001)
healthy controls. Moreover, our study showed that the NLR
(Table 4).

Table 4. Results of the logistic regression analysis comparing the suicide attempter and suicide non-attempter groups.
b S.E.
Model 1 Suicide history 2.322 0.331
Model 2 Suicide history 5.060 0.814
NLR 1.241 0.289
2LL
Model 1 104.828
Model 2 65.466
p < 0.05.
p < 0.001.
was a significant predictor of a recent suicide attempt in the
logistic regression analysis. Thus, the present study shows
that inflammation may play a central role in the pathogen-
esis of suicidal behavior in MDD. In addition, our results
remained significant when confounding factors were consid-
ered, including depression severity, smoking, gender, age
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and BMI. Therefore, our findings also reflect that the NLR
may be a trait marker for suicidal behavior in patients with
MDD and not just a state marker resulting from the stress
triggered by depression and the suicide itself. Recent studies
have shown that the NLR is a good indicator of inflammation
state and that the NLRs of patients with schizophrenia and
Alzheimer’s disease are high compared with those of control
groups [(38,39]. Stress and depression have been suggested
to increase leukocyte and neutrophil levels, whereas they
decrease lymphocytes [40]. However, a limited number of
studies have examined the NLR in patients with major
depression, and it has been suggested that the NLRs of
patients with major depression are significantly higher than
are those of control subjects [29,30]. In only one study,
Ivkovi
c et al. [41] found that NLR may be a biomarker of sui-
cidal attempt in patients with bipolar disorder. However, no
study has assessed the connection between NLR and suicide
in patients with MDD. Of note, our results demonstrate that
the NLR may be a valuable and easily accessible biomarker
for suicidal behavior in patients with MDD. We suggest that
future prospective studies be performed to determine
whether the high NLR is a reason for or result of suicide
attempt in patients with MDD.
In contrast, the connection between CRP and suicide was
weaker than the connection between suicide and NLR in the
present study. There was no relationship between groups
when CRP levels were examined as a categorical variable. We
analyzed CRP as a continuous and categorical variable based
on guidelines for the quantification of inflammation [16].
Similar to the current findings, Vargas et al. [17] did not find
differences in CRP levels between patients with and without
a history of suicide attempts. On the contrary, Gibbs et al.
[42] found that inpatients who had attempted suicide had
significantly higher levels of CRP. These authors did not cat-
egorize patients based on CRP status or consider the effects
of confounding factors on CRP levels; moreover, they did not
measure other inflammation markers in their study. Courtet
et al. [43] found that CRP may be a trait marker of a history
of suicide attempts; they found a substantial risk of
attempted suicide in patients presenting low-grade inflam-
mation with CRP >3 mg/L. They preferred to consider CRP as
NORDIC JOURNAL OF PSYCHIATRY 5
95.0% C.I. for EXP(b)
Wald df Sig. Exp(b) Lower Upper
49.119 1 0.000 0.098 0.051 0.188
38.680 1 0.000 0.006 0.001 0.031
18.387 1 0.000 3.460 1.962 6.102
v2 (df) v2chang(df) Nagelkerke’s R2
87.867 (1) 87.86(1) 0.625
127.23 (2) 39.36(1) 0.799
a categorical and continuous measure in patients with and
without suicide attempts. However, they indicated that some
depressive features, such as sleep deprivation and treatment
resistance, may have effect on CRP measures. Taken together,
our results may indicate that the NLR is a more reliable and
stable marker of inflammation than CRP for predicting suici-
dality in patients with MDD given the inconsistent results
regarding the connection between suicide and CRP.
Regarding the relationship between lipid profile and sui-
cide, the current study revealed that the TC level was signifi-
cantly lower in the patients in the SA group than in the
patients in the NSA group. However, these differences did
not remain significant after adjusting for potential confound-
ing factors. In addition, we found gender-related differences
in TC and LDL levels between the suicidal and nonsuicidal
groups. Several clinical studies with psychiatric subjects have
revealed that serum TC levels are significantly lower in psy-
chiatric patients who have attempted suicide than in those
who have not attempted suicide and in healthy controls
[44–46]. However, there have been negative findings for
serum TC and suicidal behavior. Some studies of patients
with MDD have reported no significant association between
serum TC and suicide attempts [6,7]. In addition, our findings
were supported by some studies showing that the relation-
ship between TC levels and suicide risk in patients with psy-
chiatric disorders is specific for females [47,48]. Therefore, the
current results suggest that lipid levels, specifically the TC
level, may be a weak and gender-specific determinant of sui-
cide attempts in patients with MDD compared with markers
of inflammation.
Limitations
Before concluding, we must consider the limitations of this
study. First, the sample size was relatively small and all the
patients were Turkish inpatients from only one clinic, which
limits the generalization of our results. Second, this was a
cross-sectional study, and we could not determine a direct
causal relationship between increased NLR and suicide risk in
MDD patients. Therefore, a prospective study should be
undertaken to confirm the causality. Third, there is the lack
of an analysis of cytokines in combination with the NLR, PLR
and CRP. Tissue damage due to suicide attempts may be
related to the levels of inflammation markers, even though
all the patients were admitted to our clinic after medical sta-
bilization and hospitalization at the internal medicine clinic.
Finally, most of the subjects received either anxiolytics and/
 6 O. EKINCI AND A. EKINCI
or antidepressants before hospitalization; these medications
could have had a significant effect either on markers of
inflammation and lipids levels. Effective antidepressant treat-
ment modulates some of the dyslipidemic patterns observed
in depressive patients, especially TC, HDL and LDL cholesterol
[49]. The evidence indicates that treatment with antidepres-
sants and electroconvulsive therapy affects cytokine and C-
reactive protein (CRP) levels [50,51]. However, it has been
reported that recovery from MDD episode after non-pharma-
cological treatment is associated with normalized cytokine
levels [52].
Conclusions
This is the first study suggesting that the NLR may be a trait
marker for suicidal vulnerability via a relationship between
the NLR and a recent suicide attempt in depressed inpa-
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tients. The NLR is inexpensive, replicable and highly suitable
for everyday clinical assessment as a biomarker of suicide risk
in MDD patients. Therefore, the determination of a new bio-
marker for individuals exhibiting suicidal behavior could be
relevant for providing a more precise estimation of suicidality
and creating new treatment modalities. However, future pro-
spective studies are needed to determine the exact roles of
NLR and other inflammation markers in suicidality in MDD.
Disclosure statement
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship,
and/or publication of this article.
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