Original article 171

Relationship between psychiatric disorders, coronary risk factors,

and inflammatory mediators among elderly diabetic patients
Moatasem S. Amera, Heba H. Elshahawib, Mohamed Khatera,
Randa A. Mabroukc and Maram M. Munira
Departments of aGeriatrics, bNeuropsychiatry and
c
Clinical Pathology, Faculty of Medicine, Ain Shams
University, Cairo, Egypt
Correspondence to Heba H. Elshahawi, MD,
Department of Neuropsychiatry, Ain Shams University,
66 Elmontazah St, Heliopolis, 11035 Cairo, Egypt
Tel: + 20 127 401 553; fax: + 20 222 683 6379;
e-mail: hebaelshahawi@yahoo.com
Received 18 November 2011
Accepted 23 December 2011
Middle East Current Psychiatry
2012, 19:171178

Background
Depression, anxiety, diabetes mellitus (DM), and coronary heart diseases (CHD) all
have common immune mechanisms of pathogenesis.
Objectives
The aim of the current study is to assess the relationship between depression and/or
anxiety, coronary risk factors, and inflammatory mediators among elderly patients with
DM.
Methods
The present study was conducted on 60 elderly diabetic patients and 30 elderly
healthy controls. The patient group was subdivided into two groups: GP1, with
30 elderly diabetic patients with medical complications, and GP2, with 30 elderly
diabetic patients without medical complications. The three groups of patients were
subjected to clinical examination, were assessed for depression and anxiety, and their
lipid profile, C-reactive protein (CRP), and interleukin-1b (IL-1b) levels were measured.
Results
Inflammatory markers (CRP and IL-1b) were higher in GP1 and GP2 than in the
healthy controls (P = 0.000 and 0.021, respectively). Inflammatory markers were
higher by a significant level in depressed patients of GP1 and GP2 (P = 0.000 for
CRP and IL-1b) and by a nonsignificant level in anxious patients (P = 0.461 and 0.07
for CRP and IL-1b, respectively). Both depressed and anxious patients showed a
significant increase in established risk factors for CHD such as a longer duration of
DM, a high BMI, higher levels of cholesterol, triglycerides, and low-density lipoproteins,
and lower levels of high-density lipoproteins.
Conclusion
Immune mechanisms play a major role in the increase in the development of CHD
associated with depression and DM.
Keywords:
coronary risk, depression, diabetes mellitus, inflammatory markers
Middle East Curr Psychiatry 19:171178
& 2012 Okasha Institute of Psychiatry, Ain Shams University
2090-5408

Introduction
Immune mechanisms seem to play a key role in the
development of many diseases. Among psychiatric disorders, the most studied disorder is depression; immune
mechanisms play a major role in the development of this
disorder. This is evidenced clinically by an episodic and
fluctuating course with partial or complete remission [1]
and by lab investigation through an increase in interleukin1b (IL-1b) in dysthymic patients and IL-1 in those with
major depression, which in turn affects the hypothalamic
pituitary adrenal axis [2].
Moreover, an elevated plasma level of inflammatory
markers, especially C-reactive protein (CRP), was a
significant predictor of type II diabetes, even after the
adjustment for BMI, waist circumference, physical

The study was conducted at the Geriatric Department and Neuropsychiatry

Department, Faculty of Medicine, Ain Shams University.

2090-5408 & 2012 Okasha Institute of Psychiatry, Ain Shams University

activity, and conventional risk factors [3,4]. This triggering of the inflammatory response can lead to the
destruction of pancreatic islet cells [5].
Furthermore, inflammation also plays a role in the
pathogenesis of atherosclerosis, development of unstable
plaques, and the risk for coronary heart disease (CHD) [6].
Depression and or anxiety, diabetes mellitus (DM), and
CHD all have almost common immune mechanisms of
pathogenesis. Depression through affection of CRP and
interleukin-6 can lead to the development of insulin
resistance, growth of atherosclerotic plaques, and thrombogenesis [7]. Anxiety disorder can play a role in CHD
through the development of hypertension, smoking
habit [8,9], and affection of electrical stability of the
heart [10], although the relationship between anxiety and
inflammatory markers is controversial [11].
CRP was studied in the current study as it is a marker of
low-grade inflammation. It might have an indirect
DOI: 10.1097/01.XME.0000415560.24359.ea

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

172 Middle East Current Psychiatry

influence on insulin resistance and secretion [12]. It

serves as a link between depression and the development
of atherosclerosis [7,13]. IL-1b was studied as its
interaction with IL-6 can affect the synthesis of CRP.
IL-1b induces proinflammatory mediators such as
corticoptropin, platelet factor-4, prostaglandin2, which
cause local and systemic inflammation [3].

completed the assessment, 80 elderly diabetic patients

were eligible but refused to complete the interview, and
100 elderly diabetic patients were ineligible. The main
reasons for refusal were time and scheduling difficulties.
A written informed consent was signed by the patients
after they were provided with an explanation of the aim of
the study.
Tools

Aim of the study

The aim of the current study is to assess the relationship
between depression and/or anxiety, coronary risk factors,
and inflammatory markers among elderly patients with DM.

Participants and methods

Participants

Participants were selected from the outpatient clinic of

the Geriatric Department (Ain Shams University, Cairo,
Egypt). Sixty diabetic elderly patients were selected;
they were divided equally into two groups: GP1, which
included 30 elderly diabetic patients with medical
complications, and GP2, which included diabetic elderly
patients without medical complications.
They were compared with 30 healthy elderly controls
with no apparent physical or neuropsychiatric comorbidities.
They were matched with the patient group for age, religion,
marital status, education, and occupation as best as possible.
The control participants were selected randomly from
among the relatives of workers and employees working
at Ain Shams University Hospitals. Therefore, this study is
a cross-sectional comparative study.
Patients were considered to be diabetic if they had a
history of DM treated with medication or a persistently
elevated fasting blood glucose of greater than 126 mg/dl
according to WHO [14]. Patients were considered to be
diabetic with medical complications if they had associated medical complications such as retinopathy, neuropathy, or nephropathy.
Participants were considered eligible for the study if they
were diabetic elderly patients, on regular oral hypoglycemic drugs or insulin, and could understand the scales.
Participants were considered ineligible for the study if they
were uncooperative, failed to complete the interview, were
on regular medications known to affect inflammatory
markers, or had a history of angina pectoris or CHD.
Control participants were considered ineligible if they had
evidence of a chronic medical condition after assessment of
history and results of examinations and relevant investigations, and if they could not comprehend the scales.
Procedure

Approximately 4050 elderly diabetic patients attend the

Geriatric outpatients clinic per month. Of these, 2030
are elderly diabetic patients with medical complications
and 1020 are elderly diabetic patients without medical
complications. During a period of 6 months, 60 elderly
diabetic patients with and without medical complications

All the groups studied were examined using the following

tools.
Comprehensive geriatric assessment

(1) History taking and complete physical examination

including a general examination, neurological and
fundus examinations, assessment of BMI, and interpretation of results according to the National Center of
Chronic Disease Prevention and Health Promotion [15].
(2) Functional assessment was performed using
activities of daily living [16] and instrumental
activities of daily living [17].
Beck depression inventory [18]

it is a 21-item self-report scale. The patients indicate the

statements that describe their current state. Each statement is scaled from 0 to 3. Patients who score 9 or more
are considered to be depressed. Patients are considered to
have mild depression if their scores lie between 9 and 16,
moderate depression if they score between 17 and 29, and
severe depression if they score above 29. A well-validated,
translated Arabic version was used [19].
State Trait Anxiety Inventory, the Spielberger anxiety scale [20]

it is a self-report assessment tool, which includes separate

measures of state and trait anxiety. According to the
author, state anxiety reflects a transitory emotional state
or condition of the human organism that is characterized
by subjective, consciously perceived feelings of tension
and apprehension and heightened autonomic nervous
system activity. State anxiety may fluctuate over time
and can vary in intensity. In contrast, trait anxiety reflects
relatively stable individual differences in anxiety proneness, and refers to a general tendency to respond
with anxiety to perceived threats in the environment.
A validated translated Arabic version was used [21].
Electrocardiography

Resting standard 12-lead electrocardiography.

Laboratory measures

Laboratory measurements of fasting blood sugar, kidney

function, liver function, erythrocyte sedimentation rate,
2 h postprandial blood sugar, and lipid profile were
performed.
Inflammatory markers

High-sensitivity CRP [22]: the DiaMed EuroGen diagnostic kit (Eurogentec, Turnhout, Belgium) was used.

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

Relationship between psychiatric disorders Amer et al.

The kit is based on the enzyme-linked immunosorbent assay,

which applies a technique called a quantitative sandwich
immunoassay. The microtiter plate provided in the kit is
precoated with a monoclonal antibody specific for CRP.
IL-1b [23]: the Accucyte Human IL-1b kit (Oncogene
research, Boston, USA) was used based on a competitive
enzyme immunoassay technique.
Statistical analysis

Data were collected, revised, verified, and edited on a

personal computer. The data collected were analyzed
using the SPSS, version 15.0 (2007; SPSS Inc., Chicago,
Illinois, USA) by a professional statistician. Data were
expressed as mean SD for qualitative measures and as
number (%) for categorized data.

173

term in the test statistic is known. However, when the

scaling term is unknown and is replaced by an estimate on
the basis of the data, the test statistic (under certain
conditions) follows a Student t-distribution.
P-value

It is the probability of obtaining a test statistic at least as

extreme as the one that was actually observed, assuming
that the null hypothesis is true. The lower the P-value,
the less likely the result is if the null hypothesis is true,
and consequently, the more significant the result is
in terms of statistical significance. A null hypothesis is
often rejected if the P-value is less than 0.05, corresponding
to a 5% probability.

Mean (arithmetic average)

Results

The mean is obtained by dividing the sum of the scores or

values by the number of scores or values. Mean is a point
of balance between the highest and the lowest score or
value in a distribution.

The study included 90 patients divided into three groups:

GP1 included 30 diabetic elderly patients on regular
treatment and with comorbid medical complications, GP2
included 30 diabetic elderly patients on regular treatment
and without any diabetic medical complications, and the
remaining 30 were healthy controls.

Standard deviation

It is the square root of the variance. It provides an

estimate of the average deviation around the mean.
The following statistical procedures have been used for
analyses of the data:
Pearsons v2-test

It is a nonparametric statistic that is used to test the

significance of differences between two or more independent nominal variables.
One-way analysis of variance

It is used to compare several means to determine how

several independent variables interact with each other and
the effects these interactions have on a dependent variable.
Spearmans correlation test

It is used to study the relationship (direction and power)

between many quantitative variables simultaneously.
Students t-test

It is most commonly applied when the test statistic

follows a normal distribution and if the value of a scaling

The two patient groups (GP1 and GP2) matched the

healthy controls in terms of education, smoking habits,
age, and BMI, as shown in Table 1.
Treatment-related data of GP1 matched those of GP2; the
duration of DM in GP1 was 10.933 6.78 years and that
in GP2 was 9.4 6.7896 years (F = 0.376 and P = 0.688).
In GP1, 26 (43.33%) patients were on oral hypoglycemic
drugs and 34 (56.67%) were on insulin treatment. These
figures matched those of GP2, in which 36 (56.67%)
patients were on oral hypoglycemic drugs and 26 (43.3%)
were on insulin treatment (w2 = 0.06 and P = 0.438).
Coronary risk factors were compared across the three
groups. The levels of fasting blood glucose and blood
glucose after the 2 h postprandial test were significantly
higher in GP1 and GP2 compared with the healthy
controls, GP3. However, no difference was found between
the three groups in the level of cholesterol, triglycerides,
low-density lipoproteins (LDL), and high-density lipoproteins (HDL; Table 2).
Inflammatory markers were significantly higher among the
elderly diabetic patients (n = 60) compared with the healthy

Table 1 Sociodemographic data of the three groups studied

Sociodemographic data
Education
Illiterate
o12 years education
Z12 years education
Smoking (smoker/nonsmoker)
Age (mean SD)
BMI
Obese
Overweight
Normal
Underweight

GP1 (n = 30)

GP2 (n = 30)

Controls (n = 30)

Statistical value

P-value

18
11
1
10/20
65.467 4.175

17
12
1
12/18
65.2 6.15

18
11
1
8/22
66.067 5.388

w2 = 0.097

0.999

w2 = 1.200
F = 0.2

0.548
0.811

5
14
10
0

6
12
12
0

3
11
13
3

w2 = 7.545

0.273

GP1, elderly patients with type II diabetes mellitus on regular treatment and with comorbid conditions; GP2, elderly patients with type II diabetes
mellitus on regular treatment and without comorbid conditions.

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

174 Middle East Current Psychiatry

Table 2 Comparison between blood sugar levels and lipid profile of the three studied groups
Lab data
Fasting blood sugar
2 h postprandial
Cholesterol
TG
HDL
LDL

GP1 (n = 30)

GP2 (n = 30)

Controls (n = 30)

P-value

206.16 40.146
273.20 48.782
194.67 37.782
121.53 28.47
54.73 15.483
109.47 20.510

172.52 53.824
242.77 68.505
189.50 38.626
120.33 23.947
63.80 30.003
119.77 24.811

70.667 5.927
143.33 11.321
175.00 30.7
115.33 23.887
62.60 18.524
107.07 20.715

61.356
42.848
2.42
0.498
2.626
2.796

0.0008
0.0007
0.095
0.61
0.078
0.067

GP1, elderly patients with type II diabetes mellitus on regular treatment and with comorbid conditions; GP2, elderly patients with type II diabetes
mellitus on regular treatment and without comorbid conditions; HDL, high-density lipoproteins; LDL, low-density lipoproteins; TG, triglycerides.

Table 3 Comparison of the three studied groups in terms of the levels of interleukin-1b and C-reactive protein
ANOVA
Inflammatory markers
IL-1b
Range
Mean SD
CRP
Range
Mean SD

GP 1

GP 2

Controls

P-value

60.00350.00
190.50 69.930

50.00300.00
157.67 65.545

85.00280.00
144.67 34.639

12.533

o0.001

0.4010.00
6.80 2.901

0.4010.00
5.16 2.283

1.0010.00
3.55 1.682

4.593

0.021

ANOVA, analysis of variance; CRP, C-reactive protein; GP1, elderly patients with type II diabetes mellitus on regular treatment and with comorbid
conditions; GP2, elderly patients with type II diabetes mellitus on regular treatment and without comorbid conditions; IL-1b, interleukin-1b.

controls (n = 30). IL-1b levels were 17.4.67 69.205 and

114.667 69.205 in the elderly diabetic patients and the
controls, respectively (t = 4.425, Po0.001). Furthermore,
CRP levels were 5.827 2.767 and 3.55 1.682 in the
elderly diabetic patients and the controls, respectively
(t = 4.134, Po0.001). On further subdivision of patient
groups into GP1 and GP2, inflammatory markers were
significantly higher in these groups than in the healthy
controls (Table 3).

Graph 1

35

We attempted to study the relationship between anxiety

and/or depression in relation to inflammatory markers in
the patient groups (GP1 and GP2). IL-1b and CRP were
significantly elevated in depressed patients (n = 14)
compared with individuals who were not depressed
(n = 46; P = 0.000). Although the level of inflammatory
markers was higher in patients with anxiety than in those
who did not have anxiety, no statistically significant
difference was found in IL-1b and CRP levels between
anxious patients (n = 16) and nonanxious patients (n = 44).
This is further shown in Table 4.
We also attempted to study the relationship between
anxiety and/or depression in relation to coronary risk
factors in the patient groups (GP1 and GP2). Depressed
elderly diabetic patients (n = 16) had a comparable mean

29

30

29

24

25

23 23

20

20
15
10
5
0

Assessment of psychiatric comorbidities indicated that

the incidence of depression was as follows: seven (23.3%),
seven (23.3%), and one (3.33%) patient in GP1, GP2, and
controls, respectively, whereas anxiety was prevalent in 10
(33.3%), six (20.6%), and one (3.33%) patient in GP1,
GP2, and controls, respectively. Both depression and
anxiety were higher in GP1 and GP2 than in healthy
controls as can be seen in Graph 1.

For depression X2 =28.282, P<0.001, and for anxiety X2 =12.831 and

p=0.0016

10
7

6
1
depressed patients

GP1
GP2
Controls

7
1

not depressed

anxious patients

not anxious

The number of depressed and anxious patients in group 1 (GP1), group

1 (GP2), and controls. GP1, diabetic patients with medical complications; GP2, diabetic patients without medical complications.

age (P = 0.301), longer duration of DM (P = 0.000),

higher BMI (P = 0.000), higher level of cholesterol
(P = 0.000), higher TG (P = 0.000), higher LDL
(P = 0.005), and lower HDL (P = 0.017) in comparison
with nondepressed elderly diabetic patients (Table 5).
Moreover, anxious diabetic elderly patients had a comparable
mean age (P = 0.318), longer duration of DM (P = 000),
higher BMI (P = 0.012), higher levels of cholesterol
(P = 0.000), triglycerides (P = 0.000), and LDL (P =
0.000), and a lower level of HDL (P = 0.000) in comparison
with nonanxious diabetic elderly patients (Table 5).

Discussion
The aim of the current study is to assess the relationship
between coronary risk factors (including inflammatory
markers) and psychiatric disorders (depression and/or
anxiety) among elderly diabetic patients.

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

Relationship between psychiatric disorders Amer et al. 175

Table 4 Comparison of interleukin-1b and C-reactive protein levels of elderly diabetic patients with anxiety and/or depression with
those in elderly diabetic patients without anxiety and/or depression
Inflammatory
markers
IL-1b
CRP

Depressed patients
(n = 16)

Nondepressed patients
(n = 44)

Anxious patients
(n = 14)

Nonanxious patients
(n = 46)

228.75 60.649
7.556 2.102

95 32.613
3.658 2.346

6.906*
4.622

125 47.652
4.36 2.474

95 32.613
3.65 2.346

1.084*
0.749

CRP, C-reactive protein; IL-1b, interleukin-1b.

*Po0.000.

Table 5 Relationship between depression and/or anxiety and coronary risk factors
Coronary risk
factors
Age
Duration of DM
BMI
Cholesterol
TG
HDL
LDL

Anxious patients
(n = 14)

Nonanxious patients
(n = 46)

Depressed patients
(n = 16)

Nondepressed patients
(n = 44)

65 3.402
11.533 6.128
26.733 2.764
207.333 18.696
139 7.606
45.467 9.687
125.733 21.439

62.833 4.589
3.333 0.985
23.5 4.425
147.917 15.733
94.833 10.676
75.583 19.119
92.167 11.938

1.41
4.571**
2.718
8.789**
12.552**
5.323**
4.844**

65 5.88
15.563 7.51
29.5 5.386
219.375 22.588
140.688 22.588
56.75 19.41
110.063 17.38

62.8 4.5
3.33 0.985
23.5 3.425
147.917 15.733
94.833 10.676
75.583 19.119
92.267 11.938

1.055
5.579**
4.618**
7.314**
6.487**
2.557
3.06*

DM, diabetes mellitus; GP1, elderly patients with type II diabetes mellitus on regular treatment and with comorbid conditions; GP2, elderly patients
with type II diabetes mellitus on regular treatment and without comorbid conditions; HDL, high-density lipoproteins; LDL, low-density lipoproteins;
TG, triglycerides.
*Po0.05, **Po0.000.

Although patients with DM are at an increased risk for

CHD, as a result of obesity, dyslipidemia, and hypertension [24], these traditional risk factors do not fully explain
the high risk for CHD associated with DM [25].
In the present study, GP1, GP2, and GP3 were matched
in terms of age, sex, education, and percentage of
smokers. BMI and lipid profile also did not differ across
the three groups (Tables 1 and 2). This was in agreement
with the results of the study by Amer et al. [26], and may
be linked to the high percentage of obese and overweight
individuals (46.6%) in the healthy group. Therefore,
established risk factors for CHD did not differ between
the patients and the controls in the present study. This
would suggest that other factors might be responsible for
the occurrence of CHD. Therefore, we studied inflammatory markers and psychiatric disorders (depression and
anxiety).
Assessment of the inflammatory markers showed that IL1b and CRP were higher in GP1 and GP2 than in the
healthy controls (Table 3), which is in agreement with
the results of the studies by Spranger et al. [3], Hu
et al. [4], and Kristiansen et al. [27].
Moreover, the diabetic comorbid group (GP1) had higher
levels of IL-1b and CRP, which is in agreement with the
results of the study by Amer et al. [26]. This elevation in
inflammatory markers could be related to diabetes
itself [4,5] or to depression as a result of alterations in
hypothalamic function by cytokines [3,7]. Inflammatory
markers also serve a link between depression and
CHD [13,28,29]. Moreover, IL-1b is an independent risk
factor for CHD [30], whereas CRP is associated with
early atherogenesis and plays a role in the prediction of
cardiovascular events [31,32].
The prevalence of depression in the entire sample of
diabetic patients was 26.67%. Ten (33.3%) and six

patients (20%) in GP1 and GP2, respectively, were

depressed (Graph 1). Comparable results were obtained
from a previous study [33]. Diabetes can lead to depression
through microvascular changes in frontal subcortical regions,
leading to damage of key regulatory hormones [34]. Nevertheless, psychosocial factors such as poverty, lack of social
support, and perceived disability are common in depression
and diabetes [35]. However, depression might result in a
disturbed hypothalamic pituitary adrenal axis, resulting in
an increased glucose level and potentiation of DM [34].
Anxiety disorders were prevalent in seven patients
(23.3%) in both GP1 and GP2 (Graph 1). The prevalence
of anxiety disorders is variable in different studies, ranging
from 5.9 to 40% [36,37]. Diabetic patients are more
vigilant compared with nondiabetic patients in terms of
normal daily activities such as eating, sleeping, and
exercise. Thus, this lifestyle can lead to anxiety [38]. In
contrast, autonomic hyperarousal may lead to an increase
in the blood glucose level and potentiate diabetes [39].
In the next step, we compared the levels of inflammatory
markers in elderly diabetic patients with psychiatric
disorders with those in diabetic patients without
psychiatric disorders. The levels of IL-1b and CRP in
elderly depressed diabetic patients were higher than
those in diabetic patients who did not have depression
(Table 4). Elderly anxious diabetic patients had higher
levels of IL-1b and CRP in comparison with those who
did not have anxiety disorders, but not to a significant
level. Depression might lead to low-grade systemic
inflammation [40,41]. Anxiety disorders can lead to an
increase in the over-response of T-helper cells [11]. The
further increase in inflammatory markers as a result of
comorbidity with anxiety and or depression could lead to
complications such as hyperglycemic crisis, diabetic ketoacidosis, a nonketotic hyperosmolar state, and cardiovascular
disease [42,43].

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

176 Middle East Current Psychiatry

Furthermore, elderly diabetic patients with anxiety and or

depression showed a significant increase in established
risk factors for CHD including high BMI, high cholesterol, high triglycerides, high LDL, low HDL, and increased
duration of diabetes (Table 5). Past studies have shown
that depressed patients with diabetes were 1.52-fold
more likely to have coronary risk factors compared with
those without depression. Anxiety and/or depression are
risk factors for an increase in body weight [44] and are
associated with a sedentary lifestyle [9]. The longer the
duration of diabetes, the greater the distress and hence
the risk of the occurrence of anxiety and depression [45].
Inflammatory responses in DM aggravated by the presence
of depression and/or anxiety could play a role in the
occurrence of CHD and in the greater severity of DM.

Conclusion
Depression, to a greater extent, and anxiety associated
with DM increase the risk for occurrence of CHDs.
Immune responses can play a major role in this condition.
Therefore, we recommend a strict psychiatric assessment
for diabetic patients throughout the course of illness and
rapid treatment of comorbidities. Regular assessment of
inflammatory markers and correction for coronary risk
factors, especially in diabetic patients with depression
and/or anxiety, are essential. More research is required on
the use of IL-1 antagonists, especially as some researchers have demonstrated improvements in pancreatic islet
cell function and glycemic control with the use of IL-1
antagonists. It should also be determined whether IL-1
antagonists can decrease the incidence of psychiatric
comorbidities and coronary risk factors or not.

Limitations of the study

Although this study yielded significant findings, it is not
without limitations:
(1) A larger study would have preferably targeted a
community sample; this would have required a large
team of researchers.
(2) Our study was a cross-sectional one. A more
comprehensive study would involve a longitudinal
study to assess depression during the course of DM
and its relationship with coronary risk factors and
inflammatory markers.
(3) The use of IL-1 antagonists should be studied in
clinical trials to determine its effects on depression
and coronary risk factors.

The authors also thank the participants of the study, the patients, and
the relatives of employees, who were the control participants, without
whom this study would not have been possible.
Professor Moatasem S. Amer designed the study and reviewed the
protocol, Dr Heba Elshahawi carried out literature searches and
analysis and wrote the first draft of the manuscript, Dr Mohamed Khater
revised the final manuscript, Dr Randa A. Mabrouk made arrangements
for lab investigations, and Dr Maram Munir carried out clinical
assessment and statistical analysis. All authors contributed to and
have approved of the final manuscript.

Conflicts of interest
There are no conflicts of interest.

References
1 Licinio J, Wong ML. The role of inflammatory mediators in the biology of major
depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems and
contribute to neurotoxicity and neuroprotection. Mol Psychiatry. 4; 1999.
pp. 317327.
2 Weisse CS. Depression and immunocompetence: a review of the literature.
Psychol Bull 1992; 111:475489.
3 Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, et al.
Inflammatory cytokines and the risk to develop type 2 diabetes: results of the
prospective population-based European Prospective Investigation into
Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003; 52:812817.
4 Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of
developing type 2 diabetes in women. Diabetes 2004; 53:693700.
5 Geiler J, McDermott MF. Gevokizumab, an anti-IL-1b mAb for the potential
treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular
disease. Curr Opin Mol Therap 2010; 12:755769.
6 Wilson AM, Ryan MC, Boyle AJ. The novel role of C-reactive protein in
cardiovascular disease: risk marker or pathogen. Int J Cardiol 2006;
106:291297.
7 Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the
regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model.
Health Psychol 2002; 21:531541.
8 Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. The
epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289:30953105.
9 McCabe RE, Chudzik SM, Antony MM, Young L, Swinson RP, Zolvensky MJ.
Smoking behaviors across anxiety disorders. J Anxiety Disord 2004; 18:
718.
10 Friedman BH, Thayer JF. Anxiety and autonomic flexibility: a cardiovascular
approach. Biol Psychol 1998; 49:303323.
11 Kulmatycki KM, Jamali F. Drug disease interactions: role of inflammatory
mediators in depression and variability in antidepressant drug response.
J Pharm Pharm Sci 2006; 9:292306.
12 Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate
immune system? Diabetologia 1998; 41:12411248.
13 Danner M, Kasl SV, Abramson JL, Vaccarino V. Association between depression and elevated C-reactive protein. Psychosom Med 2003; 65:
347356.
14 Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of
diabetes mellitus. Provisional report of a WHO consultation. Diabet Med
1998; 15:539553.
15 National Center of Chronic Disease Prevention and Health Promotion. BMI
for adults. What does all this mean? United States Department of Health
and Human Service Center for Disease Control and Prevention: Division of
Nutrition and Physical Activity; 2003.
16 Katz S. Katz index of activities of daily living. JAMA 1963; 185:914915.
17 Lawton MP, Brody EM. Assessment of older people: self-maintaining and
instrumental activities of daily living. Gerontologist 1969; 9:179186.
18 Beck AT, Steer RA. Manual for the Beck Depression Inventory. San Antonio,
TX: Psychological Corporation; 1993.
19 Abdelfatah G. The Arabic version of Beck depression inventory. Al Azhar
Educ J 1894; 3:155163.
20 Spielberger CD. Manual for the State-Trait Anxiety Inventory (STAI). Palo
Alto, CA: Consulting Psychologists Press; 1983.

Acknowledgements
The authors thank Professor Moatasem Amer, the Professor of
Geriatrics, one of the pioneers of Geriatric Medicine in Egypt, and
the chairman of the Geriatric Department, Ain Shams University, for
conceptualizing this study. They were privileged to work under his
supervision. His wisdom, trust, and support helped them work on this
interesting domain.

21 Abdel Khalek A. State trait anxiety inventory. Cairo, Egypt: Al Anglo Bookstore; 1992.
22 Gewurz H, Mold C, Siegel J, Fiedel B. C-reactive protein and the acute
phase response. Adv Intern Med 1982; 27:345372.
23 Di Iorio A, Ferrucci L, Sparvieri E, Cherubini A, Volpato S, Corsi A, et al.
Serum IL-1beta levels in health and disease: a population-based study. The
InCHIANTI study. Cytokine 2003; 22:198205.

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

Relationship between psychiatric disorders Amer et al.

24 Adler AI, Stevens RJ, Neil A, Stratton IM, Boulton AJM, Holman RR. UKPDS
59: hyperglycemia and other potentially modifiable risk factors for peripheral
vascular disease in type 2 diabetes. Diabetes Care 2002; 25:894899.
25 Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors
and 12-yr cardiovascular mortality for men screened in the multiple risk factor
intervention trial. Diabetes Care 1993; 16:434444.
26 Amer MS, Maher M, Khater MS. Inflammatory mediators and relation to
cognitive function in elderly diabetic patientsFaculty of Medicine. Ain Shams
University; 2006.
27 Kristiansen OP, Mandrup Poulsen T. Interleukin-6 and diabetes: the good,
the bad or the indifferent? Diabetes 2005; 54 (Suppl 2): S114S124.
28 Ford DE, Erlinger TP. Depression and C-reactive protein in US adults: data
from the Third National Health and Nutrition Examination Survey. Arch Intern
Med 2004; 164:10101014.
29 Shimbo D, Chaplin W, Crossman D, Haas D, Davidson KW. Role of depression and inflammation in incident coronary heart disease events. Am J
Cardiol 2005; 96:10161021.
30 Von der Thusen JH, Kuiper J, Van Berkel TJC, Biessen EAL. Interleukins in
atherosclerosis: molecular pathways and therapeutic potential. Pharmacol
Rev 2003; 55:133166.
31 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001; 104:365372.
32 Taskinen S, Kovanen PT, Jarva H, Meri S, Pentikainen MO. Binding of Creactive protein to modified low-density-lipoprotein particles: identification of
cholesterol as a novel ligand for C-reactive protein. Biochem J 2002;
367:403412.
33 Larijani B, Bayat MKS, Gorgani MK, Bandarian F, Akhondzadeh S, Sadjadi
SA. Association between depression and diabetes. German J Psychiatry
2004; 7:6265.
34 Thomas AJ, Kalaria RN, OBrien JT. Depression and vascular disease:
what is the relationship? J Affect Disord 2004; 79 (13): 8195.

177

35 Talbot F, Nouwen A. A review of the relationship between depression and

diabetes in adults: Is there a link? Diabetes Care 2000; 23:15561562.
36 Hermanns N, Kulzer B, Krichbaum M, Kubiak T, Haak T. Affective and anxiety
disorders in a German sample of diabetic patients: prevalence, comorbidity
and risk factors. Diabet Med 2005; 22:293300.
37 Wittchen HU, Zhao S, Kessler RC, Eaton WW. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry
1994; 51:355364.
38 Rubin RR, Peyrot M. Psychological issues and treatments for people with
diabetes. J Clin Psychol 2001; 57:457478.
39 Lustman PJ. Anxiety disorders in adults with diabetes mellitus. Psychiatr Clin
North Am 1988; 11:419432.
40 Schiepers OJG, Wichers MC, Maes M. Cytokine and major depression. Prog
Neuropsychopharmacol Biol Psychiatry 2005; 29:201217.
41 Thomas AJ, Davis S, Morris C, Jackson E, Harrison R, OBrien JT. Increase
in interleukin-1b in late-life depression. Am J Psychiatry 2005; 162:
175177.
42 Stentz FB, Umpierrez GE, Cuervo R, Kitabchi AE. Proinflammatory cytokines,
markers of cardiovascular risks, oxidative stress and lipid peroxidation in
patients with hyperglycemic crises. Diabetes 2004; 53:20792086.
43 Kitabchi AE, Umpierrez GE, Fisher JN, Murphy MB, Stentz FB. Thirty years
of personal experience in hyperglycemic crises: diabetic ketoacidosis and
hyperglycemic hyperosmolar state. J Clin Endocrinol Metab 2008; 93:
15411552.
44 Strine TW, Mokdad AH, Dube SR, Balluz LS, Gonzalez O, Berry JT, et al. The
association of depression and anxiety with obesity and unhealthy behaviors
among community-dwelling US adults. Gen Hosp Psychiatry 2008; 30:
127137.
45 Manderson L, Kokanovic R, Klimidis S. Emotional and lifestyle impact of type
2 diabetes: exploring the association between diabetes and depression.
Diabetes Educ Assoc Magazine 2005; 8:1113.

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.

178 Middle East Current Psychiatry

Copyright Middle East Current Psychiatry. Unauthorized reproduction of this article is prohibited.