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Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577

DOI 10.1007/s00406-017-0779-9

ORIGINAL PAPER

Nicotine dependence is associated with depression and childhood


trauma in smokers with schizophrenia: results from the FACE-SZ
dataset
Romain Rey1,2   · Thierry D’Amato1,2 · Laurent Boyer1,3 · Lore Brunel1,4 · Bruno Aouizerate1,5 · Fabrice Berna1,6 ·
Delphine Capdevielle1,7 · Isabelle Chereau1,8 · Gabrielle Chesnoy‑Servanin1,2 · Hélène Denizot1,8 ·
Jean‑Michel Dorey1,2 · Caroline Dubertret1,9 · Julien Dubreucq1,10 · Catherine Faget1,11 · Franck Gabayet1,10 ·
Christophe Lancon1,11 · Jasmina Mallet1,9 · David Misdrahi1,12 · Christine Passerieux1,13 · Aurélie Schandrin1,7 ·
Franck Schürhoff1,4 · Mathieu Urbach1,13 · Pierre Vidailhet1,6 · Pierre‑Michel Llorca1,8 · Guillaume Fond1,14 · The
FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group

Received: 20 June 2016 / Accepted: 6 March 2017 / Published online: 7 April 2017
© Springer-Verlag Berlin Heidelberg 2017

Abstract  In a perspective of personalized care for smok- questionnaire score ≥ 7. Depression was defined by a Cal-
ing cessation, a better clinical characterization of smok- gary score ≥ 6. Childhood trauma was self-reported by the
ers with schizophrenia (SZ) is needed. The objective of Childhood Trauma Questionnaire score (CTQ). Ongoing
this study was to determine the clinical characteristics psychotropic treatment was recorded. Severe NIC depend-
of SZ smokers with severe nicotine (NIC) dependence. ence was identified in 83 subjects (34.6%), depression in
240 stabilized community-dwelling SZ smokers (mean 60 (26.3%). 44 (22.3%) subjects were treated by antide-
age = 31.9 years, 80.4% male gender) were consecutively pressants. In a multivariate model, severe NIC dependence
included in the network of the FondaMental Expert Cent- remained associated with depression (OR = 3.2, p = 0.006),
ers for Schizophrenia and assessed with validated scales. male gender (OR = 4.5, p = 0.009) and more slightly with
Severe NIC dependence was defined by a Fagerstrom childhood trauma (OR = 1.03, p = 0.044), independently

8
* Romain Rey CMP B, CHU, EA 7280 Faculté de Médecine, Université
romain.rey@ch‑le‑vinatier.fr d’Auvergne, BP 69 63003 Clermont‑Ferrand Cedex 1, France
9
1 AP‑HP, Department of Psychiatry, Louis Mourier Hospital,
Fondation FondaMental, Créteil, France Colombes, Inserm U894, Université Paris Diderot, Sorbonne
2
INSERM U1028, CNRS UMR5292, Université Claude Paris Cité, Faculté de médecine, France
Bernard Lyon 1, Centre de Recherche en Neurosciences de 10
Centre Référent de Réhabilitation Psychosociale, CH Alpes
Lyon, Equipe PSYR2, Centre Hospitalier Le Vinatier, Pole Isère, Grenoble, France
Est, 95 bd Pinel, BP 30039, 69678 Bron Cedex, France
11
3 Assistance Publique des Hôpitaux de Marseille (AP‑HM),
Pôle Psychiatrie Universitaire, CHU Sainte‑Marguerite, pôle universitaire de psychiatrie, Marseille, France
F‑13274 Marseille cedex 09, France
12
4 Centre Hospitalier Charles Perrens, F‑33076 Bordeaux,
INSERM U955, équipe de psychiatrie translationnelle, France, Université de Bordeaux, CNRS UMR 5287-INCIA,
Créteil, France, Université Paris-Est Créteil, DHU Pe-PSY, Bordeaux, France
Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor,
13
40 rue de Mesly, F‑94010, Créteil, France Service de psychiatrie d’adulte, Centre Hospitalier de
5 Versailles, UFR des Sciences de la Santé Simone Veil,
Centre Hospitalier Charles Perrens, F‑33076 Bordeaux, Université Versailles Saint-Quentin en Yvelines, Versailles,
France, Université de Bordeaux, Inserm, Neurocentre France
Magendie, Physiopathologie de la Plasticité Neuronale,
14
U862, F‑33000 Bordeaux, France Clinique Jeanne D’Arc‑Hôpital Privé Parisien, Saint Mandé,
6 F94000, France, CHU Carémeau, Nîmes F30000, France
Hôpitaux Universitaires de Strasbourg, Université de
Strasbourg, INSERM U1114, Fédération de Médecine
Translationnelle de Strasbourg, Strasbourg, France
7
Service Universitaire de Psychiatrie Adulte, Hôpital la
Colombière, CHRU Montpellier, Université Montpellier 1,
Inserm 1061, Montpellier, France

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Vol.:(0123456789)

568 Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577

of socio-demographic characteristics, psychotic symptoms about chances of success of tobacco cessation programs for
severity, psychotropic treatments and alcohol disorder. NIC SZ smokers [16, 37]. Indeed, numerous studies have found
dependence was independently and strongly associated that SZ smokers report lower motivation to quit compared
with, respectively, depression and male gender in schizo- to the general population [38]. Poor treatment outcome in
phrenia, and only slightly with history of childhood trauma. smokers with SZ is assumed to be the practical manifes-
Based on these results, the care of both nicotine depend- tation of this low motivation [35]. Moreover, smoking is
ence and depression should be evaluated for an effective viewed by some as a less harmful alternative to alcohol
smoking cessation intervention in schizophrenia. or illicit drug use or as a way to support abstinence from
alcohol or illicit drugs [39]. It has also been suggested that
Keywords  Schizophrenia · Nicotine dependence · smoking may be an attempt to self-medicate, thus, some
Tobacco smoking · Depression · Childhood trauma clinicians are concerned that quitting may remove a coping
strategy and have detrimental effects on psychiatric symp-
toms [40].
Introduction These difficulties for clinicians to apply public health
strategies in daily practice may be reduced by a better-per-
Tobacco smoking, a global epidemic, is one of the greatest sonalized care approach. Personalized medical care may be
challenges of our time. Currently about 1.1  billion people defined as “giving the right treatment to the right patient at
worldwide are cigarette smokers. Approximately 6  mil- the right time” [41]. In this way, a better characterization of
lion people die each year from tobacco use in the world, smokers with severe nicotine (NIC) dependence at baseline
and the number of annual deaths is estimated to increase may help clinicians (1) identify the comorbid factors that
to 10 million by the year 2030, which makes smoking the may be responsible for heavy smoking maintenance in SZ
leading preventable cause of death worldwide [1, 2]. Given smokers and (2) suggest personalized pharmacological and
that tobacco abstinence dramatically decreases many health non-pharmacological therapies targeting tobacco cessation
risks [3–5], treating smoking addiction should be consid- as well as other comorbidities in a holistic approach.
ered as one of the most important activities a clinician can The objective of the present study was, therefore, (1)
perform [6–8]. to determine the prevalence of severe NIC dependence in
Patients diagnosed with schizophrenia (SZ) are more a large non-selected community-dwelling sample of sta-
frequently smokers compared to the general population and bilized SZ smokers and (2) to determine the clinical char-
other psychiatric disorders [9, 10]. Moreover, SZ smokers acteristics of SZ smokers with severe NIC dependence
exhibit more severe smoking behaviors [11] and mortality compared to other SZ smokers, in a purpose of identifying
attributed to smoking is particularly high among this group potential factors of maintenance that may be further tar-
with increased risk of cardiovascular and cancer disease geted in tobacco cessation programs.
[12, 13]. SZ smokers have greater difficulties in quitting
smoking compared to non-SZ smokers [14–17]. Currently,
it is unclear whether this lower rate of smoking cessation Experimental procedures
in SZ is due to lower effectiveness of smoking cessation
treatments or lower availability and/or use of such effective Study population
treatments in this population [18].
The link between schizophrenia and smoking is increas- The FACE-SZ (FondaMental Academic Centers of Exper-
ingly well understood from a biological point of view. It has tise for Schizophrenia) cohort is based on a French national
been suggested (and extensively debated) that SZ patients network of 10 Schizophrenia Expert Centers(Bordeaux,
may smoke to alleviate some of their negative, depressive Clermont-Ferrand, Colombes, Créteil, Grenoble, Lyon,
and/or cognitive symptoms (the so-called “self-medication Marseille, Montpellier, Strasbourg, Versailles), set up by a
hypothesis”) [19–22]. Common gene vulnerability between scientific cooperation foundation in France, the FondaMen-
tobacco smoking/nicotine dependence and schizophrenia tal Foundation (http://www.fondation-fondamental.org)
has also been extensively described [23–29]. and created by the French Ministry of Research to create a
With suicide, severe tobacco smoking has been sug- platform that links thorough and systematic assessment to
gested to be one of the major culprits for early morbidity research. Stable patients aged above 16 years are referred
and mortality in schizophrenia [30]. Helping SZ patients by their general practitioner or psychiatrist, who subse-
quit smoking is, therefore, one of the current major chal- quently receives a detailed evaluation report with sugges-
lenges in the care of schizophrenia. However, success rates tions for personalized interventions. The patients diagnosed
of smoking cessation programs remain poor in daily prac- with schizophrenia or schizoaffective disorder, according to
tice [31–36] and clinicians still often remain pessimistic DSM-IV-TR criteria, are enrolled in the FACE-SZ cohort.

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Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577 569

The assessment protocol was approved by the relevant convergent validity and the different cut-offs have been
ethical review board (CPP-Ile de France IX, January 18, shown to have good specificity and sensitivity [54]. Com-
2010). pliance to treatment was evaluated by clinicians using the
Brief Adherence Rating Scale (BARS) [55]. BARS scores
Data collected range from 0 to 100, 100 is the best compliance (the patient
did not forget the treatment intake in the last 30 days). A
Patients were interviewed by members of the specialized good adherence was defined by a BARS score ≥ 90. Alco-
multidisciplinary team of the Expert Center. Diagnoses hol and/or cannabis dependence was defined according to
and interviews were carried out by two independent psy- the SCID 1.0. Information on education (number of years
chiatrists according to the Structured Clinical Interview for of education) and illness duration (in years) and ongoing
Mental Disorders (SCID 1.0) [42]. NIC dependence was treatment were recorded. All patients were on stable medi-
measured by the Fagerstrom Test for Nicotine Depend- cation for more than 4 weeks.
ence (FTND), the most widely used self-reported measure
of nicotine dependence [43]. Severe NIC dependence was Statistical analysis
defined by a score ≥ 7.
Psychotic symptomatology was assessed using the Posi- Socio-demographics, clinical characteristics and comorbid-
tive and Negative Symptoms Scale (PANSS) [44]. For the ities were presented using measures of means and disper-
purpose of this study, we used a well-validated five-factor sion (standard deviation) for continuous data and frequency
model of the PANSS [45] which can be described as fol- distribution for categorical variables. Univariate associa-
lows: ‘‘positive symptoms” which include symptoms such tions between demographic and clinical characteristics of
as hallucinations and delusions; ‘‘negative symptoms” SZ smokers with severe vs. mild NIC dependence were
which include symptoms such as blunted affect; ‘‘disor- performed using Chi-square test for categorical variables
ganization” which include symptoms such as difficulty in and Wilcoxon test for continuous variables. To explore the
abstraction, and conceptual disorganization; ‘‘excitement” relationship between NIC dependence and gender, age at
which include symptoms such as excitement and hostility; illness onset, education level, current depression, antide-
‘‘emotional distress” which include both depressive and pressant consumption, and the history of childhood trauma,
anxiety symptoms. The reliability and internal consistency we used a multivariate logistic regression model adjusting
of the French adaptation of the PANSS is good [46]. Cur- for potential confounders. Data were analyzed using SPSS
rent depressive symptoms were evaluated using the Calgary 20.0 software (SPSS Inc., Chicago, IL). All statistical tests
Depression Rating Scale for Schizophrenia (CDRS) [47]. were two tailed, with α level set at 0.05.
This scale was designed to identify specific depressive
symptomatology that cannot be related to negative symp-
toms of schizophrenia. Depression was defined by a CDRS Results
score ≥  6. Manic symptoms were evaluated using the
Young Mania Rating Scale (YMRS) [48]. A current manic A sample of 240 SZ smokers enrolled in the FACE-SZ
episode was defined by a YMRS score ≥ 12. The valida- cohort was included in this study. Table  1 shows demo-
tion study of the PANSS found very satisfactory inter-rater graphical and clinical characteristics of the sample, as well
coefficients of agreement (ranging from 0.79 to 0.83) [49]. as the current treatments that have been administered.
Recently, Suzuki et al. also reported an excellent inter-rater The majority of the subjects in the sample (N = 193,
reliability for the PANSS (intraclass correlation coefficient 80.4%) were men and the mean age of patients was
of 0.92) [50]. Likewise, a high level of inter-rater reliability 31.91 ± 8.81 years. The mean duration of illness was
has been observed for the CDRS (weighted kappa values 10.5 ± 7.5 years and the mean PANSS total score was
>0.75) [51] as well as for the YMRS (intraclass correlation 72.6 ± 20.1. Current dependence for cannabis was found in
>0.89) [52]. 28 patients (11.7%), and for alcohol in 32 patients (13.3%).
History of childhood trauma was obtained using the Severe NIC dependence was found in 83 subjects
French version of the Childhood Trauma Questionnaire (34.6%) in our sample of 240 SZ smokers, depression in 60
(CTQ) [53]. The CTQ is a retrospective self-report instru- (26.3%), and 44 (22.3%) were treated by antidepressants.
ment that examines the traumatic childhood experiences The results of univariate and multivariate analyses are
of adults and adolescents. It consists of 28 items, each one presented in Table 1. In our univariate analyses, SZ smok-
rated from 1 (never) to 5 (very often) that measure five ers with severe NIC dependence showed statistically sig-
types of childhood trauma: emotional abuse, emotional nificant higher rates of depression (p = 0.006), antidepres-
neglect, physical abuse, physical neglect, and sexual abuse. sant consumption (p = 0.045), and reported more frequently
The CTQ has shown excellent test–retest reliability and childhood trauma (p = 0.037).

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Table 1  Factors associated with level of NIC dependence measured by the Fagerstrom Test for Nicotine Dependence (FTND) in 240 community-dwelling schizophrenic smokers: univariate
570

and multivariate analyses


Whole sample Univariate analysis Multivariate analysis

13
Mild NIC dependence Severe NIC depend-
(FTND < 7) ence (FTND ≥ 7)
(N = 240) (N = 157) (N = 83)
mean/n SD/% mean/n SD/% mean/n SD/% P aOR 95% CI P

Socio-demographic characteristics
 Sex (male), n (%) 193 80.4% 124 79.0% 69 83.1% 0.441 4.5 1.5 13.7 0.009
 Age (years) mean (SD) 31.91 8.81 31.20 9.05 33.25 8.22 0.087 1.00 0.95 1.06 0.924
 Age at regular tobacco smoking onset (years) mean (SD) 17.14 3.67 17.33 3.67 16.80 3.66 0.299
 University level, n (%) 130 54.2% 82 52.2% 48 57.8% 0.407 1.4 0.68 3.0 0.359
 Unemployment, n (%) 169 74.8% 111 75.0% 58 74.4% 0.916
 Premorbid intellectual functioning*, mean (SD) 104.45 8.45 104.22 8.75 104.92 7.69 0.762
Illness characteristics
 Childhood trauma (CTQ score), mean (SD) 42.57 11.83 41.34 10.66 44.96 13.60 0.037 1.03 1.00 1.06 0.044
 Age at onset (years), mean (SD) 21.42 5.40 21.03 5.50 22.14 5.17 0.141 1.02 0.93 1.11 0.722
 Age at first antipsychotic treatment, mean (SD) 22.48 5.66 22.39 5.78 22.63 5.49 0.772
 Illness duration (years), mean (SD) 10.46 7.49 10.21 7.76 10.93 6.96 0.495
 PANSS-positive score, mean (SD) 12.37 5.32 12.15 5.27 12.52 5.54 0.626
 PANSS-negative score, mean (SD) 22.51 7.38 22.36 8.38 21.80 6.94 0.614
 PANSS emotional distress score, mean (SD) 8.89 3.66 8.71 3.55 9.35 3.71 0.209
 PANSS disorganization score, mean (SD) 20.31 6.71 20.58 7.07 20.06 6.32 0.585
 PANSS excitement score, mean (SD) 6.15 2.71 6.01 2.67 6.22 2.77 0.568
 PANSS total score, mean (SD) 72.64 20.14 72.62 20.55 72.67 19.49 0.986
 GAF score, mean (SD) 48.50 11.77 48.58 12.14 48.35 11.08 0.891
 Current depressive episode (CDRS score ≥ 6), n (%) 60 26.3% 31 20.5% 30 37.0% 0.006 3.2 1.4 7.1 0.006
 History of suicidal attempt, n (%) 18 7.8% 14 9.2% 4 5.1% 0.275
 Current manic episode (YMRS score ≥ 12), mean (%) 12 5.5% 6 4.3% 6 7.7% 0.296
Comorbidities
 Current alcohol d­ ependencea, n (%) 32 13.3% 19 12.1% 13 15.7% 0.440
 Current cannabis ­dependencea, n (%) 28 11.7% 28 17.8% 0 0.0% < 0.0001
Treatment variables
 Second-generation antipsychotic (vs first generation), n (%) 169 85.8% 110 85.9% 59 85.5% 0.934
 Antidepressant, n (%) 44 22.3% 23 18.0% 21 30.4% 0.045 1.3 0.54 2.9 0.605
Anxiolytic, n (%) 61 31.0% 38 29.7% 23 33.3% 0.598
 Hypnotic, n (%) 18 9.1% 12 9.4% 6 8.7% 0.875
Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577
Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577 571

In our multivariate analyses, severe NIC dependence

aOR adjusted odds ratio, 95% CI 95% confidence interval, CTQ Childhood Trauma Questionnaire, PANSS Positive And Negative Symptoms Scale for Schizophrenia, GAF Global Assessment
was strongly associated with depression (OR = 3.2; 95%

P
CI 1.4–7.1, p = 0.006), male gender (OR = 4.5; 95% CI
1.5–13.7, p  = 0.009) and more slightly with childhood
trauma (OR = 1.03; 95% CI 1.00–1.06, p = 0.044), inde-
pendently of socio-demographic characteristics, symptoms
95% CI
severity, treatments and alcohol dependence.
Multivariate analysis

Discussion
aOR

Our major findings may be summarized as follows: in


a large non-selected community-dwelling sample of SZ
0.567

of Functioning, CDRS Calgary Depression Rating Scale for Schizophrenia, YMRS Young Mania Rating Scale. BARS: Brief Adherence Rating Scale

smokers, severe NIC dependence was found in one-third of


P

the subjects. Severe NIC dependence was strongly associ-


ated with depression and male gender, and more slightly
Severe NIC depend-

43.2%
SD/%

with a history of childhood trauma, independently of other


ence (FTND ≥ 7)

confounding variables including socio-demographical vari-


ables, psychotic symptomatology, current alcohol depend-
(N = 83)

ence and medication.


mean/n

First, 34.6% of SZ smokers reported severe NIC depend-


35

ence in the present study. This rate is lower than those of


Mild NIC dependence

41.6% reported in one recent French study [56] (this pro-


39.3%
Univariate analysis

SD/%

portion has been calculated with raw data after contacting


the authors). The selected populations (community-dwell-
(FTND < 7)

ing SZ subjects vs. SZ inpatients), the recruitment design


(N = 157)
mean/n

(multicentric vs. monocentric) and the sex ratio (male rate


59

80.4 vs. 71.9%) may, therefore, explain this discrepancy.


Periods of recruitment (during early years of 2010s), mean
ages (respectively, 31.9 vs. 35.6 years) and psychotic sever-
40.7%
SD/%

ity were comparable between studies (mean PANSS total


Whole sample

score 72.06 vs. 71.09). Depression, antidepressant use and


 As defined in the Structural Clinical Interview for mental Disorders (SCID-1)

history of childhood trauma were not reported by Faugere


(N = 240)
mean/n

et al. study [56]. The present smokers’ sample size is larger


94

(240 vs. 154 SZ smokers). The larger sample size and the
multicentric recruitment may suggest that the present rate
of NIC dependence in SZ smokers may be closer to the real
prevalence of NIC dependence in middle-aged French com-
*As defined by the Barona intellectual quotient total score

munity-dwelling SZ smokers. Further studies are needed to


confirm this result.
Second, severe NIC dependence was strongly associ-
 Poor observance (BARS score < 90), n (%)

ated with depression. This association has been demon-


strated here for the first time, although some indirect clues
Mean (SD): mean ± standard deviation

have retrospectively paved the way to the present finding.


Significant associations are in bold

In one study carried out in 87 American SZ smokers, the


Fagerstrom score for NIC dependence has been positively
correlated with the levels of blunted affect and social with-
drawal, but no specific assessment of depression had been
Table 1  (continued)

included in the evaluation at the time [57]. However, it was


unclear whether these symptoms were depressive symp-
toms or negative symptoms of schizophrenia. In a large
follow-up cohort of 542 American SZ smokers, the varia-
tion of the amount of tobacco consumption was found to
a

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572 Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577

co-vary only with depressive symptomatology (beta = 0.16, and a meta-analysis are needed to determine if smoking
p < 0.001) but not with positive, negative or disorganized behavior is associated with higher depressive symptomatol-
symptomatology [58]. ogy in schizophrenia.
Combined with literature data, the present associa- In the present study, NIC dependence was associated
tion between severe NIC dependence and depression sug- with depression (assessed with the Calgary scale), while no
gests potential major therapeutic applications. Depression association with any of the five PANSS factors was found.
at baseline has been found to be associated with smoking This is consistent with previous results reporting no dif-
relapse in a small sample of 28 SZ smokers after only 1 ference in total positive scores and total negative scores
week of tobacco cessation [59]. This preliminary result between severe and mild NIC-dependent SZ smokers [60].
suggests that a better characterization of SZ smokers is In contrast, one previous study reported an association
needed to orientate personalized treatments. In another between severe NIC dependence and positive, disorganiza-
recent study, motives for smoking in English SZ smok- tion, excitement PANSS factors in 173 SZ smokers [68].
ers were helping relaxing (60%), to cope with a feeling of In a sample of 87 SZ smoker outpatients, Fawzi et al. also
loneliness (16%), to better socialize (14%) and because of reported differences in PANSS factors between very high,
anxiety or depression (31%) [60]. This “mood-increasing” high and mild NIC-dependent SZ subjects [69]. Notably, in
motive was already reported as a major motive for SZ this latter study, the emotional distress factor was signifi-
tobacco smoking in other studies [61, 62]. These previ- cantly different between the three groups of smokers. These
ous studies suggest a potential association between NIC different results may be due to discrepant characteristics
dependence and depression that is confirmed in the pre- of the included subjects (especially due to sex, age and
sent results. Furthermore, the association between NIC antipsychotic treatments), differences in inclusion criteria
dependence and depression is not limited to schizophrenia (Fawzi et al. excluded patients with schizoaffective disorder
and has been described in non-SZ smokers’ population. In or with comorbid affective disorders), recruitment design
a sample of 202 American subjects seeking smoking ces- (monocentric vs. multicentric) and sample size (240 SZ
sation treatment, depressed smokers reported significantly smokers in the present study vs. 173 and 87). Moreover, as
higher mean FTND scores compared with non-depressed there is no consensual definition of severe NIC dependence,
smokers (5.6 vs. 4.9) [63]. Using the DSM-IV definition of the above studies used different FTND cut-off to discrimi-
nicotine dependence, 16.5% of NIC-dependent individuals nate highly dependent smokers from the others. A further
in the national epidemiologic survey on alcohol and related meta-analysis should, therefore, be carried out among SZ
conditions (NESARC) suffered from a current episode of smokers to determine if severe NIC dependence is associ-
depression, which is several times higher than the rate of ated with a specific pattern of PANSS factors compared to
current major depressive disorder in the general population mild NIC dependence.
(ranging from 2 to 7%) [64, 65]. Third, in the present study, severe NIC dependence
It may, therefore, be reasonably suggested that treating was associated with a self-reported history of childhood
depression may help SZ smokers quit smoking. In the pre- trauma in SZ smokers, independently of depression. To
sent sample, 44 (22.3%) were currently administered anti- date, this association was not demonstrated in schizophre-
depressant. However, 61 (26.3%) SZ smokers had current nia, while it has been extensively demonstrated in the gen-
depressive symptoms at the time of the evaluation, which eral population of smokers [70]. A potential “dose–effect”
suggests that the treatment of depression in SZ smokers has even been reported in non-SZ smokers, with a positive
may be improved. graded relationship between the number of adverse child-
As non-smoking SZ patients have not been included in hood experiences and the severity and prevalence of NIC
the present study, a comparison between smokers vs. non- dependence in adulthood [71, 72]. Childhood trauma has
smokers SZ subjects has not been possible. To date, only been associated with, respectively, early-onset smoking,
two studies investigated the influence of smoking on affec- smoking initiation, current smoking in adulthood, heavy
tive symptoms in community-dwelling SZ patients. In a smoking and NIC dependence, independently of socio-
sample of 102 SZ outpatients, Kao et  al. reported higher demographic characteristics [73–75]. From a biological
depressive scores in SZ smokers compared to non-smokers point of view, experiencing childhood adversity may lead
[66]. However, Li et al. failed to find a significant associa- to long-lasting changes in numerous systems such as endo-
tion between depressive symptoms and smoking in a larger crine system, immune system, brain structure and function-
cohort of 621 community-dwelling SZ patients [67]. This ing through epigenetic gene expression regulation [76]. The
inconstancy may be explained by methodological discrep- nicotinic network may be impacted as well. However, it
ancies (especially depression definition and assessment as should be underscored that this association was very mild
different scales were used), and differences in the recruit- in the present study (OR = 1.03), although significant. This
ment design (monocentric vs. multicentric). Further studies may be explained by memory bias or under-declaration of

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Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577 573

childhood trauma in our sample and by the multiple adjust- reported conflicting results due to the moderate quality of
ments with variables related to childhood trauma (includ- the available data and the small sample sizes. The present
ing education level and depression). results may suggest that the association between FGA
Fourth, NIC dependence has been strongly associated administration and higher tobacco smoking may not be
with male gender in the present study. This is consistent mediated by NIC dependence. Further studies are needed
with prior results in SZ smokers [68, 77]. Our high rate to explore the potential relationship between antipsy-
of males (80.4%) is also consistent with previous studies chotic administration and tobacco smoking behavior in
including SZ smokers with comparable sample sizes. For SZ smokers.
example, in a recent study investigating predictors of smok- As schizophrenia and NIC dependence may involve
ing reduction outcomes in a sample of 287 SZ patients, common gene vulnerability [90, 91], it may have been
males represented 88.9% of SZ smokers [78], which sug- hypothesized that NIC dependence may have been linked
gests that gender strongly influences tobacco smoking with earlier age of schizophrenia onset. The present
in schizophrenia. This over-representation is also found results are not in favor of this hypothesis, as no associa-
in non-SZ smokers [64]. For instance, King et  al. found tion has been found between NIC dependence and the age
that smoking prevalence among 118 581 adults in the US at schizophrenia onset.
was significantly higher among men (22.3%) than women
(16.9%) [79]. Consistent with these results, in a sample of
8 229 European smokers, males represented 76.9% of the Limits
daily smokers [80]. In this latter study, males accounted
for 85.7% of smokers with severe NIC dependence. In gen- First, a problem remains with the definition of severe NIC
eral population, numerous studies have explored sex dif- dependence. There is no consensual cut-off to discrimi-
ferences in smoking behavior. Several meta-analyses have nate highly dependent smokers from the others. However,
confirmed that genetic and environmental factors may con- in the present study, we have chosen the cut-off of ≥7,
tribute differently to the determination of smoking initia- consistently with a recent French study including sub-
tion and persistence in male and female smokers [81–83]. jects with bipolar disorders [92]. Then, carbon monoxide,
Smoking initiation has been found to have a higher herita- which may be used in tobacco cessation centers for objec-
bility in females while smoking persistence has been found tive smoking behavior assessment, has not been measured
to have a higher heritability in males [81]. Although social in the present study. However, carbon monoxide levels
factors impact smoking substantially in humans, findings do not always discriminate adequately between differ-
from animal models provide support that sex differences ent levels of severity of NIC dependence [93]. It should
in nicotine/tobacco addiction have a biological basis. Dif- be noted that non-smoking SZ patients have not been
ferences in the pharmacokinetic properties of NIC or the included in the present study, as NIC dependence could
effect of gonadal hormones may underlie some but not all only be assessed in current SZ smokers according to the
sex differences observed [84, 85]. Estrogen may increase FTND questionnaire. Due to the cross-sectional design
NIC dependence in females while progesterone may of our study, it was not possible to conclude to a causal
decrease it [86]. A study exploring specifically sex differ- relationship between NIC dependence and depression.
ences in psychotic disorders has found less gender effect Future studies should determine if depression in schizo-
compared to the general population [87]. This study used a phrenia is a risk factor for increased NIC dependence or
broad definition of psychosis (including SZ, schizoaffective if NIC dependence is a risk factor for depression onset
disorder, bipolar disorder and depression with psychosis). (due to the middle-term toxic effects of heavy smoking
However, some studies have suggested that NIC depend- behavior). Although regular training sessions have been
ence may result from specific pathophysiological pathways carried out to improve inter-rater reliability, no inter-rater
in schizophrenia (for review see Parikh et  al., 2016 [88]). coefficients for the PANSS and CDRS have been calcu-
Further studies are needed in schizophrenia to examine the lated. Since this is a multi-center network, these proper-
gender effect on NIC dependence. From this perspective, ties should be assessed in the future. However, previous
gender should be taken into account in treatment strategies studies reported high level of inter-rater reliability for
of smoking cessation programs. these scales. The retrospective, self-reported assessment
Fifth, NIC dependence was not associated with sec- of childhood trauma may lead to distortion of recollec-
ond-generation antipsychotics (SGA) administration tion or memory bias due to cognitive barriers and adap-
in our community-dwelling stabilized sample of SZ tive denial coping mechanisms. However, our findings
smokers, while first-generation antipsychotics (FGA) are consistent with current literature on the role of early
have been suggested to increase tobacco smoking onset stress in severe mental illnesses and addictive behaviors
and maintenance [89]. However, the reviewed studies [76].

13

574 Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577

Strengths National de la Santé et de la Recherche Médicale). We express all our


thanks to the nurses, and to the patients who were included in the pre-
sent study. We thank Hakim Laouamri, and his team (Stéphane Beau-
The studies using the FTND questionnaire for NIC fort, Seif Ben Salem, Karmène Souyris, Victor Barteau and Mohamed
dependence assessment in schizophrenia are few in num- Laaidi) for the development of the FACE-SZ computer interface, data
ber. It should be underlined that these studies have used management, quality control and regulatory aspects.
the PANSS Emotional Distress score to assess depressive FACE-SZ group: M. A ­ndrianarisoaa,m, B. ­ Aouizerateb,m, F.
c,m d,m a,m
­Berna , O. ­Blanc , L. B ­ runel , E. B ­ ulzacka , D. ­Capdeviellee,m,
a,m
symptomatology. This score is only designed to assess the I. Chereau-Boudetd,m, G. Chesnoy-Servaninf,m, J.M. D ­anionc,m,
severity of both depressive and anxious symptomatology f,m
T. D’Amato , A. ­ g,m
Deloge , C. ­ h,m
Delorme , H. ­ Denizotd,m, J.M.
due to schizophrenia (including anhedonia and blunted ­Doreyf,m, C. ­Dubertreti,m, J. D ­ ubreucqh,m, C. ­Fagetj,m, C. ­Fluttazh,m,
affect for instance). This is a dimensional rather than a cat- G. ­Fondk,m, S. ­ Fonteneaul,m, F. ­ Gabayeth,m, E. Giraud-Baroh,m,
M.C. Hardy-Baylel,m, D. L ­ acelled,m, C. Lançonj,m, H. L ­ aouamrim,
egorical variable, as no cut-off has been defined to date. a,m
M. ­Leboyer , T. Le G a,m
­ loahec , Y. Le S i,m
­trat , P.M. ­ Llorcad,m,
The present work used the Calgary scale, a specific scale J. ­Malleti,m, E. ­ Metairiej,m, D. ­ Misdrahig,m, I. Offerlin-Meyerc,m,
to assess depression in schizophrenia, which is a strength C. ­Passerieuxl,m, P. P ­erij,m, S. P ­iresd,m, C. ­Portalieri,m, R. ­Reyf,m,
compared to other previous works using the Beck Depres- C. ­Romanh,m, M. ­ Sebilleaul,m, A. S ­chandrine,m, F. Schürhoffa,m,
A. ­Tessierg,m, A.M. ­ Tronched,m, M. ­ Urbachl,m, F. ­Vaillantj,m, A.
sion Inventory Scale or the Montgomery–Asberg Depres- ­Vehierf,m, P. ­Vidailhetc,m, J. ­Vilaina,m, E. Vilàg,m, H. Y ­ azbeke,m, A.
sion Rating Scale [66, 67], which may not be adapted to SZ Zinetti-Bertschy .c,m
a
subjects. These works should ideally use scales designed to INSERM U955, équipe de psychiatrie translationnelle, Créteil,
identify specific depressive symptomatology that cannot be France, Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psy-
chiatrie des Hôpitaux Universitaires H Mondor, 40 rue de Mesly,
related to negative symptoms of schizophrenia such as the F-94010, Créteil, France.
CDRS. The use of homogenous and exhaustive standard- b
Centre Hospitalier Charles Perrens, F-33076 Bordeaux, France;
ized diagnostic protocols across the centers and inclusion Université de Bordeaux, Inserm, Neurocentre Magendie, Physi-
of a large number of potential confounding factors in the opathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux,
France.
multivariate analysis (socio-demographic variables, psy- c
Hôpitaux Universitaires de Strasbourg, Université de Strasbourg,
chotic symptomatology, adherence to treatment) may also INSERM U1114, Fédération de Médecine Translationnelle de Stras-
be mentioned in the strengths of the present work. More bourg, Strasbourg, France.
d
specifically, alcohol dependence, a strong risk factor for CMP B, CHU, EA 7280 Faculté de Médecine, Université
d’Auvergne, BP 69 63003 Clermont-Ferrand Cedex 1, France.
depression, has been included in our analyses. The present e
Service Universitaire de Psychiatrie Adulte, Hôpital la Colom-
study has provided for the first time a prevalence of severe bière, CHRU Montpellier, Université Montpellier 1, Inserm 1061,
NIC dependence in a large non-selected sample of French Montpellier, France.
f
community-dwelling SZ subjects. The sample size was INSERM U1028, CNRS UMR5292, Université Claude Bernard
Lyon 1, Centre de Recherche en Neurosciences de Lyon, Equipe
comparable with those of previous studies in other coun- PSYR2; Centre Hospitalier Le Vinatier, Pole Est, 95 bd Pinel, BP
tries [68, 78]. In the end, our national multi-centric sample 30039, 69678 Bron Cedex, France.
g
of SZ patients referred to the Expert Centers may be under- Centre Hospitalier Charles Perrens, F-33076 Bordeaux, France;
scored as another strength. Université de Bordeaux, CNRS UMR 5287-INCIA.
h
Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère,
Grenoble, France.
i
AP-HP, Department of Psychiatry, Louis Mourier Hospital,
Conclusion Colombes, Inserm U894 Université Paris Diderot, Sorbonne Paris
Cité, Faculté de médecine, France.
j
Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle
NIC dependence is strongly associated with comorbid universitaire de psychiatrie, Marseille, France.
depression, male gender, and more slightly with childhood k
Clinique Jeanne D’Arc-Hôpital Privé Parisien, Saint Mandé,
trauma in stabilized community-dwelling SZ smokers, F94000, France, CHU Carémeau, Nîmes, F30000, France.
l
independently of psychotic symptomatology and alcohol Service de psychiatrie d’adulte, Centre Hospitalier de Versailles,
Le Chesnay, EA 4047 HANDIReSP, UFR des Sciences de la Santé
dependence. This better characterization of SZ smokers Simone Veil, Université Versailles Saint-Quentin en Yvelines, Ver-
is a first step toward a personalized approach for effective sailles, France.
m
tobacco cessation programs. More specifically, targeting Fondation Fondamental.
comorbid depression by pharmacological and non-pharma-
Compliance with ethical standards 
cological strategies may improve the success of smoking
cessation programs in SZ smokers. The assessment protocol was approved by the relevant ethical review
board (CPP-Ile de France IX, January 18th, 2010). This study has,
therefore, been performed in accordance with the ethical standards laid
Acknowledgements  This work was funded by Le Vinatier Hos- down in the 1964 Declaration of Helsinki and its later amendments.
pital, AP-HP (Assistance Publique des Hôpitaux de Paris), Fonda- All subjects gave their informed consent prior to their inclusion in the
tion FondaMental (RTRS Santé Mentale), by the Investissements study.
d’Avenir program managed by the ANR under reference ANR-11-
IDEX-0004-02 and ANR-10-COHO-10-01, and by INSERM (Institut

13
Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577 575

Conflict of interest  On behalf of all authors, the corresponding au- 14. Kishi T, Iwata N (2015) Varenicline for smoking cessation
thor states that there is no conflict of interest. in people with schizophrenia: systematic review and meta-
analysis. Eur Arch Psychiatry Clin Neurosci 265:259–268.
doi:10.1007/s00406-014-0551-3
15. Lasebikan VO (2014) Tobacco smoking and medical co-mor-
References bidities among patients with schizophrenia in a Nigerian clini-
cal setting. Afr J Med Med Sci 43:315–325
1. World Health Organization (2011) Economics of tobacco 16. Mitchell AJ, Vancampfort D, De Hert M, Stubbs B (2015) Do
toolkit: assessment of the economic costs of smoking. Geneva: people with mental illness receive adequate smoking cessa-
World Health Organization. http://www.who.int/iris/han- tion advice? A systematic review and meta-analysis. Gen Hosp
dle/10665/44596. Accessed 2 October 2016 Psychiatry 37:14–23. doi:10.1016/j.genhosppsych.2014.11.006
2. World Health Organization (2011) WHO report on the Global 17. Wijesundera H, Hanwella R, de Silva VA (2014) Antipsychotic
Tobacco Epidemic, 2011. Geneva: World Health Organization. medication and Tobacco use among outpatients with schizo-
http://www.who.int/tobacco/global_report/2011/en/. Accessed 2 phrenia: a cross-sectional study. Ann Gen Psychiatry 13:7.
October 2016 doi:10.1186/1744-859X-13-7
3. 2008 PHS Guideline Update Panel, Liaisons, and Staff (2008) 18. Roberts E, Eden Evins A, McNeill A, Robson D (2016) Effi-
Treating tobacco use and dependence: 2008 update U.S. Public cacy and tolerability of pharmacotherapy for smoking ces-
Health Service Clinical Practice Guideline executive summary. sation in adults with serious mental illness: a systematic
Respir Care 53(9):1217–1222 review and network meta-analysis. Addiction 111:599–612.
4. Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata doi:10.1111/add.13236
DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MS, Fornage 19. Ahlers E, Hahn E, Ta TM, Goudarzi E, Dettling M, Neuhaus
M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch AH (2014) Smoking improves divided attention in schizophre-
EC, Moore WS, Wilson JA, American Heart Association Stroke nia. Psychopharmacology (Berl) 231:3871–3877. doi:10.1007/
Council, Council on Cardiovascular and Stroke Nursing, Coun- s00213-014-3525-2
cil on Clinical Cardiology, Council on Functional Genomics and 20. Hahn B, Harvey AN, Concheiro-Guisan M, Huestis MA, Hol-
Translational Biology, Council on Hypertension (2014) Guide- comb HH, Gold JM (2013) A test of the cognitive self-medi-
lines for the primary prevention of stroke: a statement for health- cation hypothesis of tobacco smoking in schizophrenia. Biol
care professionals from the American Heart Association/Ameri- Psychiatry 74:436–443. doi:10.1016/j.biopsych.2013.03.017
can Stroke Association. Stroke 45(12):3754–3832. doi:10.1161/ 21. Manzella F, Maloney SE, Taylor GT (2015) Smoking in schiz-
STR.0000000000000046 ophrenic patients: a critique of the self-medication hypothesis.
5. Cokkinides V, Bandi P, McMahon C, Jemal A, Glynn T, Ward World J Psychiatry 5(1):35–46. doi:10.5498/wjp.v5.i1.35
E (2009) Tobacco control in the United States—recent pro- 22. Winterer G (2010) Why do patients with schizophrenia

gress and opportunities. CA Cancer J Clin 59(6):352–365. smoke? Curr Opin Psychiatry 23(2):112–119. doi:10.1097/
doi:10.3322/caac.20037 YCO.0b013e3283366643
6. Glantz S, Gonzalez M (2012) Effective tobacco control is key to 23. Jackson KJ, Fanous AH, Chen J, Kendler KS, Chen X (2013)
rapid progress in reduction of non-communicable diseases. The Variants in the 15q25 gene cluster are associated with risk for
Lancet 379:1269–1271. doi:10.1016/S0140-6736(11)60615-6 schizophrenia and bipolar disorder. Psychiatr Genet 23:20–28.
7. Frieden TR (2014) Tobacco control progress and potential. doi:10.1097/YPG.0b013e32835bd5f1
JAMA 311(2):133–134. doi:10.1001/jama.2013.284534 24. Trossbach SV, Fehsel K, Henning U, Winterer G, Luckhaus
8. National Center for Chronic Disease Prevention and Health Pro- C, Schable S, Silva MA, Korth C (2014) Peripheral DISC1
motion (US) Office on Smoking and Health (2014) The Health protein levels as a trait marker for schizophrenia and modu-
Consequences of Smoking – 50 Years of Progress: A Report of lating effects of nicotine. Behav Brain Res 275:176–182.
the Surgeon General. Atlanta (GA), Centers for Disease Control doi:10.1016/j.bbr.2014.08.064
and Prevention (US) 25. Wium-Andersen MK, Orsted DD, Nordestgaard BG (2015)

9. de Leon J, Diaz FJ (2005) A meta-analysis of worldwide studies Tobacco smoking is causally associated with antipsychotic
demonstrates an association between schizophrenia and tobacco medication use and schizophrenia, but not with antidepressant
smoking behaviors. Schizophr Res 76:135–157 medication use or depression. Int J Epidemiol 44:566–577.
10. Rüther T, Bobes J, De Hert M, Svensson TH, Mann K, Batra A, doi:10.1093/ije/dyv090
Gorwood P, Möller HJ, European Psychiatric Association (2014) 26. Zhang XY, Chen da C, Xiu MH, Hui L, Liu H, Luo X, Zuo
EPA guidance on tobacco dependence and strategies for smoking L, Zhang H, Kosten TA, Kosten TR (2012) Association of
cessation in people with mental illness. Eur Psychiatry 29(2):65– functional dopamine-beta-hydroxylase (DBH) 19 bp insertion/
82. doi:10.1016/j.eurpsy.2013.11.002 deletion polymorphism with smoking severity in male schizo-
11. Hartz SM, Pato CN, Medeiros H, Cavazos-Rehg P, Sobell JL, phrenic smokers. Schizophr Res 141:48–53. doi:10.1016/j.
Knowles JA, Bierut LJ, Pato MT, Genomic Psychiatry Cohort schres.2012.07.011
Consortium (2014) Comorbidity of severe psychotic disorders 27. Zhang XY, Chen DC, Tan YL, Tan SP, Luo X, Zuo L, Rao
with measures of substance use. JAMA Psychiatry 71(3):248– W, Yu Q, Kou C, Allen M, Correll CU, Wu J, Soares JC
254. doi:10.1001/jamapsychiatry.2013.3726 (2015) A functional polymorphism in the interleukin-1beta
12. Tran E, Rouillon F, Loze JY, Casadebaig F, Philippe A, Vitry F, and severity of nicotine dependence in male schizophrenia: a
Limosin F (2009) Cancer mortality in patients with schizophre- case-control study. J Psychiatr Res 64:51–58. doi:10.1016/j.
nia: an 11-year prospective cohort study. Cancer 115(15):3555– jpsychires.2015.03.015
3562. doi:10.1002/cncr.24383 28. Zhang XY, Rao WW, Yu Q, Yu Y, Kou C, Tan YL, Chen DC,
13. Kelly DL, McMahon RP, Wehring HJ, Liu F, Mackowick KM, Zuo L, Luo X, Soares JC (2016) Association of the manga-
Boggs DL, Warren KR, Feldman S, Shim JC, Love RC, Dixon nese superoxide dismutase gene Ala-9Val polymorphism with
L (2011) Cigarette smoking and mortality risk in people with age of smoking initiation in male schizophrenia smokers. Am J
schizophrenia. Schizophr Bull 37(4):832–838. doi:10.1093/ Med Genet B Neuropsychiatr Genet 171:243–249. doi:10.1002/
schbul/sbp152 ajmg.b.32398

13

576 Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577

29. Akbarian S, Kundakovic M (2015) CHRNA7 and CHRFAM7A: and Negative Syndrome Scale II: a ten-fold cross-validation of a
psychosis and smoking? Blame the neighbors! Am J Psychiatry revised model. Schizophr Res 85(1–3):280–287
172(11):1054–1056. doi:10.1176/appi.ajp.2015.15081018 46. Lancon C, Reine G, Llorca PM, Auquier P (1999) Validity

30. Walker ER, McGee RE, Druss BG (2015) Mortality in mental and reliability of the French-language version of the Positive
disorders and global disease burden implications: a system- and Negative Syndrome Scale (PANSS). Acta Psychiatr Scand
atic review and meta-analysis. JAMA Psychiatry 72:334–341. 100(3):237–243
doi:10.1001/jamapsychiatry.2014.2502 47. Addington D, Addington J, Maticka-Tyndale E (1993) Assessing
31. Bernard PP, Esseul EC, Raymond L, Dandonneau L, Xambo JJ, depression in schizophrenia: the Calgary Depression Scale. Br J
Carayol MS, Ninot GJ (2013) Counseling and exercise inter- Psychiatry Suppl 22:39–44
vention for smoking reduction in patients with schizophrenia: a 48. Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating
feasibility study. Arch Psychiatr Nurs 27:23–31. doi:10.1016/j. scale for mania: reliability, validity and sensitivity. Br J Psychia-
apnu.2012.07.001 try 133:429–435
32. Culhane MA, Schoenfeld DA, Barr RS, Cather C, Deckersbach 49. Kay SR, Opler LA, Lindenmayer JP (1988) Reliability and valid-
T, Freudenreich O, Goff DC, Rigotti NA, Evins AE (2008) Pre- ity of the positive and negative syndrome scale for schizophren-
dictors of early abstinence in smokers with schizophrenia. J Clin ics. Psychiatry Res 23(1):99–110
Psychiatry 69:1743–1750 50. Suzuki T, Takeuchi H, Nakajima S, Nomura K, Uchida H, Yagi
33. Gelkopf M, Noam S, Rudinski D, Lerner A, Behrbalk P,
G, Watanabe K, Kashima H (2010) Magnitude of rater differ-
Bleich A, Melamed Y (2012) Nonmedication smoking reduc- ences in assessment scales for schizophrenia. J Clin Psychophar-
tion program for inpatients with chronic schizophrenia: a ran- macol 30(5):607–611. doi:10.1097/JCP.0b013e3181f0bae1
domized control design study. J Nerv Ment Dis 200:142–146. 51. Bernard D, Lancon C, Auquier P, Reine G, Addington D (1998)
doi:10.1097/NMD.0b013e3182438e92 Calgary Depression Scale for Schizophrenia: a study of the
34. Mackowick KM, Lynch MJ, Weinberger AH, George TP (2012) validity of a French-language version in a population of schizo-
Treatment of Tobacco dependence in people with mental health phrenic patients. Acta Psychiatr Scand 97(1):36–41
and addictive disorders. Curr Psychiatry Rep 14:478–485. 52. Favre S, Aubry JM, Gex-Fabry M, Ragama-Pardos E, McQuil-
doi:10.1007/s11920-012-0299-2 lan A, Bertschy G (2003) Translation and validation of a French
35. Mann-Wrobel MC, Bennett ME, Weiner EE, Buchanan RW, Ball version of the Young Mania Rating Scale (YMRS). Encephale
MP (2011) Smoking history and motivation to quit in smokers 29(6):499–505
with schizophrenia in a smoking cessation program. Schizophr 53. Paquette D, Laporte L, Bigras M, Zoccolillo M (2004) Valida-
Res 126:277–283. doi:10.1016/j.schres.2010.10.030 tion of the French version of the CTQ and prevalence of the his-
36. Wu BJ, Lan TH (2017)  Predictors of smoking reduction out- tory of maltreatment. Sante Ment Que 29:201–220
comes in a sample of 287 patients with schizophrenia spec- 54. Bernstein DP, Fink L, Handelsman L, Foote J, Lovejoy M, Wen-
trum disorders. Eur Arch Psychiatry Clin Neurosci 267:63–72. zel K, Sapareto E, Ruggiero J (1994) Initial reliability and valid-
doi:10.1007/s00406-015-0636-7  ity of a new retrospective measure of child abuse and neglect.
37. Prochaska JJ (2010) Failure to treat tobacco use in mental health Am J Psychiatry 151:1132–1136
and addiction treatment settings: a form of harm reduction? Drug 55. Byerly MJ, Nakonezny PA, Rush AJ (2008) The Brief Adherence
Alcohol Depend 110(3):177–182 Rating Scale (BARS) validated against electronic monitoring in
38. Kelly DL, Raley HG, Lo S, Wright K, Liu F, McMahon RP, assessing the antipsychotic medication adherence of outpatients
Moolchan ET, Feldman S, Richardson CM, Wehring HJ, Heish- with schizophrenia and schizoaffective disorder. Schizophr Res
man SJ (2012) Perception of smoking risks and motivation to 100(1–3):60–69. doi:10.1016/j.schres.2007.12.470
quit among nontreatment-seeking smokers with and without 56. Faugere M, Micoulaud-Franchi JA, Alessandrini M, Richieri R,
schizophrenia. Schizophr Bull 38(3):543–551. doi:10.1093/ Faget-Agius C, Auquier P, Lancon C, Boyer L (2015) Quality of
schbul/sbq124 life is associated with chronic inflammation in schizophrenia: a
39. Tajima B, Guydish J, Delucchi K, Passalacqua E, Chan M,
cross-sectional study. Sci Rep 5:10793. doi:10.1038/srep10793
Moore M (2009) Staff knowledge, attitudes, and practices 57. Patkar AA, Gopalakrishnan R, Lundy A, Leone FT, Certa KM,
regarding nicotine dependence differ by setting. J Drug Issues Weinstein SP (2002) Relationship between tobacco smoking and
39(2):365–384 positive and negative symptoms in schizophrenia. J Nerv Ment
40. Prochaska JJ (2010) Integrating tobacco treatment into mental Dis 190:604–610
health settings. JAMA 304(22):2534–2535 58. Kotov R, Guey LT, Bromet EJ, Schwartz JE (2010) Smoking in
41. Ozomaro U, Wahlestedt C, Nemeroff CB (2013) Personalized schizophrenia: diagnostic specificity, symptom correlates, and
medicine in psychiatry: problems and promises. BMC Med illness severity. Schizophr Bull 36:173–181. doi:10.1093/schbul/
11:132. doi:10.1186/1741-7015-11-132 sbn066
42. First SR, Gibbon M, Williams JBW (1995) Structured Clinical 59. Tidey JW, Colby SM, Xavier EM (2014) Effects of smoking
Interview for DSM-IV Axis I Disorders, Patient Edition (SCID- abstinence on cigarette craving, nicotine withdrawal, and nico-
P), Version 2. New York State Psychiatric Institute, Biometrics tine reinforcement in smokers with and without schizophrenia.
Research, New York Nicotine Tob Res 16:326–334. doi:10.1093/ntr/ntt152
43. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO
60. Krishnadas R, Jauhar S, Telfer S, Shivashankar S, McCreadie
(1991) The Fagerstrom test for nicotine dependence: a revi- RG (2012) Nicotine dependence and illness severity in schiz-
sion of the Fagerstrom tolerance questionnaire. Br J Addict ophrenia. Br J Psychiatry 201:306–312. doi:10.1192/bjp.
86:1119–1127 bp.111.107953
44. Kay SR, Fiszbein A, Opler LA (1987) The positive and nega- 61. Gurpegui M, Martinez-Ortega JM, Jurado D, Aguilar MC, Diaz
tive syndrome scale (PANSS) for schizophrenia. Schizophr Bull FJ, de Leon J (2007) Subjective effects and the main reason for
13(2):261–276 smoking in outpatients with schizophrenia: a case-control study.
45. van der Gaag M, Hoffman T, Remijsen M, Hijman R, de Haan Compr Psychiatry 48(2):186–191
L, van Meijel B, van Harten PN, Valmaggia L, de Hert M, Cui- 62. Barr AM, Procyshyn RM, Hui P, Johnson JL, Honer WG (2008)
jpers A, Wiersma D (2006) The five-factor model of the Positive Self-reported motivation to smoke in schizophrenia is related to

13
Eur Arch Psychiatry Clin Neurosci (2017) 267:567–577 577

antipsychotic drug treatment. Schizophr Res 100(1–3):252–260. the effects of antipsychotics on smoking reduction in patients
doi:10.1016/j.schres.2007.11.027 with schizophrenia. J Clin Psychopharmacol 33:319–328.
63. Lerman C, Audrain J, Orleans CT, Boyd R, Gold K, Main
doi:10.1097/JCP.0b013e31828b2575
D, Caporaso N (1996) Investigation of mechanisms linking 79. King BA, Dube SR, Tynan MA (2012) Current tobacco use
depressed mood to nicotine dependence. Addict Behav 21:9–19 among adults in the United States: findings from the National
64. Dome P, Lazary J, Kalapos MP, Rihmer Z (2010) Smoking, Adult Tobacco Survey. Am J Public Health 102:e93–e100.
nicotine and neuropsychiatric disorders. Neurosci Biobehav Rev doi:10.2105/AJPH.2012.301002
34:295–342. doi:10.1016/j.neubiorev.2009.07.013 80. Kaleta D, Polanska K, Korytkowski P, Usidame B, Bak-Roman-
65. Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA (2004) iszyn L (2015) Patterns of nicotine dependence in four Eastern
Nicotine dependence and psychiatric disorders in the United European countries. BMC Public Health 15:1189. doi:10.1186/
States: results from the national epidemiologic survey on alcohol s12889-015-2537-0
and related conditions. Arch Gen Psychiatry 61:1107–1115 81. Li MD, Cheng R, Ma JZ, Swan GE (2003) A meta-analysis of
66. Kao YC, Liu YP, Cheng TH, Chou MK (2011) Cigarette smok- estimated genetic and environmental effects on smoking behav-
ing in outpatients with chronic schizophrenia in Taiwan: rela- ior in male and female adult twins. Addiction 98(1):23–31
tionships to socio-demographic and clinical characteristics. Psy- 82. Cepeda-Benito A, Reynoso JT, Erath S (2004) Meta-analysis of
chiatry Res 190:193–199. doi:10.1016/j.psychres.2011.05.016 the efficacy of nicotine replacement therapy for smoking cessa-
67. Li Y, Hou CL, Ma XR, Zang Y, Jia FJ, Zhong BL, Lin YQ, Chiu tion: differences between men and women. J Consult Clin Psy-
HF, Ungvari GS, Himelhoch S, Cao XL, Cai MY, Lai KY, Xiang chol 72(4):712–722
YT (2016) Smoking and its associations with sociodemographic 83. Scharf D, Shiffman S (2004) Are there gender differences in
and clinical characteristics and quality of life in patients with smoking cessation, with and without bupropion? Pooled- and
schizophrenia treated in primary care in China. Gen Hosp Psy- meta-analyses of clinical trials of Bupropion SR. Addiction
chiatry 38:79–83. doi:10.1016/j.genhosppsych.2015.10.003 99(11):1462–1469
68. Aguilar MC, Gurpegui M, Diaz FJ, de Leon J (2005) Nicotine 84. Pauly JR (2008) Gender differences in tobacco smoking dynam-
dependence and symptoms in schizophrenia: naturalistic study of ics and the neuropharmacological actions of nicotine. Front
complex interactions. Br J Psychiatry 186:215–221 Biosci 13:505–516
69. Fawzi MH, Fawzi MM, Khedr HH, Fawzi MM (2007) Tobacco 85. Pogun S, Yararbas G (2009) Sex differences in nico-

smoking in Egyptian schizophrenia patients with and without tine action. Handb Exp Pharmacol 192:261–291.
obsessive-compulsive symptoms. Schizophr Res 95:236–246 doi:10.1007/978-3-540-69248-5_10
70. Roberts ME, Fuemmeler BF, McClernon FJ, Beckham JC (2008) 86. Lynch WJ, Sofuoglu M (2010) Role of progesterone in nicotine
Association between trauma exposure and smoking in a popu- addiction: evidence from initiation to relapse. Exp Clin Psychop-
lation-based sample of young adults. J Adolesc Health 42:266– harmacol 18(6):451–461. doi:10.1037/a0021265
274. doi:10.1016/j.jadohealth.2007.08.029 87. Filia SL, Baker AL, Gurvich CT, Richmond R, Lewin TJ,

71. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Wil- Kulkarni J (2014) Gender differences in characteristics and out-
liamson DF, Giovino GA (1999) Adverse childhood experi- comes of smokers diagnosed with psychosis participating in a
ences and smoking during adolescence and adulthood. JAMA smoking cessation intervention. Psychiatry Res 215(3):586–593.
282:1652–1658 doi:10.1016/j.psychres.2014.01.002
72. van Loon AJ, Tijhuis M, Surtees PG, Ormel J (2005) Determi- 88. Parikh V, Kutlu MG, Gould TJ (2016) nAChR dysfunction

nants of smoking status: cross-sectional data on smoking initia- as a common substrate for schizophrenia and comorbid nico-
tion and cessation. Eur J Public Health 15:256–261 tine addiction: Current trends and perspectives. Schizophr Res
73. Chartier MJ, Walker JR, Naimark B (2009) Health risk behav- 171(1–3):1–15. doi:10.1016/j.schres.2016.01.020
iors and mental health problems as mediators of the relationship 89. Matthews AM, Wilson VB, Mitchell SH (2011) The role of
between childhood abuse and adult health. Am J Public Health antipsychotics in smoking and smoking cessation. CNS Drugs
99:847–854. doi:10.2105/AJPH.2007.122408 25:299–315. doi:10.2165/11588170-000000000-00000
74. King G, Guilbert P, Ward DG, Arwidson P, Noubary F (2006) 90. Gage SH, Munafo MR (2015) Rethinking the association

Correlates of sexual abuse and smoking among French adults. between smoking and schizophrenia. Lancet. Psychiatry
Child Abuse Negl 30:709–723 2(2):118–119. doi:10.1016/S2215-0366(14)00057-1
75. Nelson EC, Heath AC, Madden PA, Cooper ML, Dinwiddie SH, 91. Kendler KS, Lonn SL, Sundquist J, Sundquist K (2015) Smoking
Bucholz KK, Glowinski A, McLaughlin T, Dunne MP, Statham and schizophrenia in population cohorts of Swedish women and
DJ, Martin NG (2002) Association between self-reported child- men: a prospective co-relative control study. Am J Psychiatry
hood sexual abuse and adverse psychosocial outcomes: results 172(11):1092–1100. doi:10.1176/appi.ajp.2015.15010126
from a twin study. Arch Gen Psychiatry 59:139–145 92. Ducasse D, Jaussent I, Guillaume S, Azorin JM, Bellivier F,
76. Provencal N, Binder EB (2015) The neurobiological effects
Belzeaux R, Bougerol T, Etain B, Gard S, Henry C, Kahn JP,
of stress as contributors to psychiatric disorders: focus on Leboyer M, Loftus J, Passerieux C, Courtet PH, Olié E, Fon-
epigenetics. Curr Opin Neurobiol 30:31–37. doi:10.1016/j. daMental Advanced Centers of Expertise in Bipolar Disorders
conb.2014.08.007 (FACE-BD) Collaborators (2015) Increased risk of suicide
77. Gurpegui M, Martinez-Ortega JM, Aguilar MC, Diaz FJ, Quin- attempt in bipolar patients with severe tobacco dependence. J
tana HM, de Leon J (2005) Smoking initiation and schizophre- Affect Disord 183:113–118. doi:10.1016/j.jad.2015.04.038
nia: a replication study in a Spanish sample. Schizophr Res 93. Kapusta ND, Pietschnig J, Plener PL, Blüml V, Lesch OM, Wal-
76:113–118 ter H (2010) Does breath carbon monoxide measure nicotine
78. Wu BJ, Chen HK, Lee SM (2013) Do atypical antipsychot-
dependence? J Addict Dis 29(4):493–499. doi:10.1080/1055088
ics really enhance smoking reduction more than typical ones?: 7.2010.509280

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