Nicotine & Tobacco Research, Volume 14, Number 5 (May 2012) 540–546
540
doi: 10.1093/ntr/ntr247
Advance Access published on December 16, 2011
© The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.
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Introduction
Depressive symptoms are closely associated with nicotine
dependence and could play an important etiological role in the
comorbidity of depression and nicotine dependence (Leventhal,
Kahler, Ray, & Zimmerman, 2009). Smokers are more likely to
report symptoms of depression and anxiety than nonsmokers
(Schmitz, Kruse, & Kugler, 2003). Similarly, current smokers
have an elevated risk of major depression relative to nonsmokers
or former smokers (Grant, Hasin, Chou, Stinson, & Dawson,
2004). Studies of major depression, anxiety disorder, and sub-
stance use disorders have found that persons who suffer from
mental illness have higher rates of lifetime and current smoking
and lower quit rates compared with persons who do not suffer
from mental illness (Breslau, Novak, & Kessler, 2004). Other
studies have shown that tobacco smoking is highly prevalent
among people with bipolar disorder and schizoaffective disorder
and is associated with a worse prognosis (Dodd et al., 2010).
Some hypotheses have been postulated for the elevated risk
of smoking in people with mood disorders. These include the
“self-medication theory,” which proposes that depression leads
to smoking because nicotine dependence may have mood mod-
ulatory effects. A second theory holds that smoking and depres-
sion have common environmental or genetic risk factors.
A third one suggests that depression is a consequence of brain
dysfunction induced by smoking (Dome, Lazary, Kalapos, &
Rihmer, 2010). Smoking may increase the risk for the development
of depression (Pasco et al., 2008). This may in part be due to the
role of dopamine in mood regulation (Malhi & Berk, 2007) and
that smoking alters the set point of the dopamine reward system in
the nucleus accumbens (Dani & De Biasi, 2001). Some have
suggested that there may be common neurobiological substrates
for substance abuse and mental disorders (Volkow, 2005).
The association between substance use disorders and psy-
chiatric disorders could be linked by the role of stress in the
Abstract
Introduction: Both smoking and depression have been associ-
ated with increased inflammatory markers. As there are few
studies on inflammatory markers that distinguish between
depressed and nondepressed smokers, it is unclear if there is
a cumulative impact of these mediators of inflammation. The
aim of this study was to investigate inflammatory markers in
tobacco smokers and compare depressed and nondepressed
smokers.
Methods: Smokers (n = 155) were recruited from the Cigarette
Smoking Cessation Service, Londrina. Mental health status
was assessed using the Diagnostic Interview for Research,
in accordance with the International Classification of the
Disorders-10th (ICD-10). Demographic information was col-
lected by self-report questionnaire, and the Fagerström Test
for Nicotine Dependence was administered. Blood specimens
were simultaneously collected and measured for C-reactive
protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and
interleukin-6 (IL-6).
Results: Depressed smokers had significantly higher levels
of hs-CRP (p = .05), IL-6 (p = .039), and TNF-α (p = .021)
compared with nondepressed smokers. Depressed smokers
were also significantly more likely than nondepressed smokers
to have been hospitalized in the previous month (p < .032),
to suffer from cardiovascular disease (p < .001) and lung
disease (p < .003), and to have more work-related disability
(p = .001).
Conclusions: These findings demonstrate that depressed
smokers had higher hs-CRP, IL-6, and TNF-α levels than non-
depressed smokers and had worse physical health outcomes and
greater work-related disability. This may have important impli-
cations in identifying shared risk pathways for depressive and
somatic disorders.
Original Investigation
A Comparison of Inflammatory Markers
in Depressed and Nondepressed Smokers
Sandra Odebrecht Vargas Nunes, M.D., Ph.D.,
1
Heber Odebrecht Vargas, M.D., M.Sc.,
1
Juliana Brum, M.D.,
2
Eduardo Prado, M.D.,
2
Mateus Mendonça Vargas,
2
Márcia Regina Pizzo de Castro, M.Sc.,
2
Seetal Dodd, Ph.D.,
3,4
&
Michael Berk, M.D., Ph.D.
3,5,6
1
Department of Psychiatry, Health Sciences Center, Londrina State University, University Hospital, Londrina, Brazil
2
Cigarette Smoking Cessation Service, Londrina State University (UEL), University Hospital, Londrina, Brazil
3
Department of Psychiatry, University of Melbourne, Parkville, Australia
4
School of Medicine, Deakin University, Geelong, Australia
5
Orygen Youth Health Research Centre, Parkville, Australia
6
Mental Health Research Institute, Parkville, Australia
Corresponding Author: Sandra Odebrecht Vargas Nunes, M.D., Ph.D., Universidade Estadual de Londrina, Av Adhemar e Barros,
625, Londrina, Paraná 86050-190, Brazil. Telephone: 55-43-33391178; Fax: 55-43-30375627; E-mail: sandranunes@sercomtel.com.br
Received February 9, 2011; accepted September 23, 2011
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