The American Journal on Addictions, 22: 46–53, 2013

Copyright © American Academy of Addiction Psychiatry

ISSN: 1055-0496 print / 1521-0391 online
DOI: 10.1111/j.1521-0391.2013.00313.x

Effects of Tobacco Smoking on Neuropsychological

Function in Schizophrenia in Comparison to Other
Psychiatric Disorders and Non‐psychiatric Controls

Dominique Morisano, PhD,1 Victoria C. Wing, PhD,1,2 Kristi A. Sacco, PsyD,3

Tamara Arenovich, MSc,1,4 Tony P. George, MD, FRCPC1–3
1
Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
2
Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
3
Program for Research in Smokers with Mental Illness (PRISM), Department of Psychiatry, Yale University School of Medicine,
New Haven, Connecticut,
4
Dalla Lana School of Public Health, Biostatistics Program, University of Toronto, Toronto, Ontario, Canada

Background and Objectives: Compared to the general population
cigarette smoking prevalence is elevated in psychiatric disorders such
as schizophrenia (SZ), bipolar disorder (BD), and major depressive
disorder (MDD). These disorders are also associated with neuro-
cognitive impairments. Cigarette smoking is associated with
improved cognition in SZ. The effects of smoking on cognition in
BD and MDD are less well studied.
Methods: We used a cross‐sectional design to study neuropsycho-
logical performance in these disorders as a function of smoking status.
Subjects (N ¼ 108) were SZ smokers (n ¼ 32), SZ non‐smokers
(n ¼ 15), BD smokers (n ¼ 10), BD non‐smokers (n ¼ 6), MDD
smokers (n ¼ 6), MDD non‐smokers (n ¼ 10), control smokers
(n ¼ 12), and control non‐smokers (n ¼ 17). Participants completed
a neuropsychological battery; smokers were non‐deprived.
Results: SZ subjects performed significantly worse than controls in
select domains, while BD and MDD subjects did not differ from
controls. Three verbal memory outcomes were improved in SZ
smokers compared with non‐smokers; smoking status did not alter
performance in BD or MDD.
Conclusions and Scientific Significance: These data suggest that
smoking is associated with neurocognitive improvements in SZ, but
not BD or MDD. Our data may suggest specificity of cigarette‐
smoking modulation of neurocognitive deficits in SZ. (Am J Addict
2013;22:46–53)
INTRODUCTION
Cigarette smoking prevalence in psychiatric disorders (PDs)
such as schizophrenia (SZ), bipolar disorder (BD), and major
depressive disorder (MDD) is two to three times higher than in
Received February 21, 2012; accepted March 21, 2012.
Address correspondence to Dr. George, Department of Psychia-
try, University of Toronto, Centre for Addiction and Mental Health
(CAMH), 250 College Street, CS 734, Toronto, ON, Canada M5T
1R8. E‐mail: tony_george@camh.net.
the general population in which the rate is approximately
20%.1,2 Clinical estimates of smoking prevalence range from
58–88% for individuals with SZ,3 51–70% for those with
BD,4–7 and 40–60% for those with MDD.7,8 This pattern has
been found to persist across cultures, even after controlling for
age, gender, country, and interaction between country and
mental illness.9 Furthermore, both epidemiological1,10 and
clinical studies11–17 have suggested a reduced likelihood of
smoking cessation in people with PDs.
There is evidence for widespread neurocognitive deficits
(executive functioning, attention and working memory function)
in people with PDs, particularly those with SZ.18 Previous studies
have demonstrated that individuals with SZ exhibited significant
deficits in executive function,19 attention, and concentration,20
working memory,21 verbal learning and memory,22 processing
speed,23 and visuospatial working memory (VSWM).24 Similar-
ly, there is evidence for neuropsychological dysfunction in both
BD and MDD. BD is associated with impairments in processing
speed, working memory, verbal fluency and episodic memory,25
verbal memory,26 and executive function,27 while MDD is
associated with deficits in episodic memory,28 verbal recall and
recognition,29 executive function,28,30,31 sustained attention, and
visuospatial learning and memory.28,30 In comparison to patients
with BD and MDD, however, those with SZ seem to have more
profound neuropsychological impairments.32,33 Recent studies
comparing the neuropsychological profiles of persons with SZ
and BD (in a euthymic phase) have either reported similar
profiles patterns but more severe impairments in SZ34 or more
widespread and severe cognitive deficits in SZ compared
with BD.35,36 In MDD, deficits in executive function are less
severe than SZ,31 while deficits in sustained attention are more
severe and stable in SZ than in BD and MDD, where deficits are
more “state‐dependent.”37
There is increasing evidence that cigarette smoking and/or
nicotine administration improves selected aspects of cognitive

46
dysfunction in SZ (reviewed in references 38–40). In contrast,
the cognitive‐enhancing effects in non‐psychiatric controls are
less clear. Some studies have demonstrated enhancements
following acute nicotine administration, while others have
reported no effects or even detrimental effects (for review, see
references 41 and 42). Moreover, recent studies have indicated
that in non‐psychiatric controls chronic smoking is associated
with worse cognitive function, particularly in higher‐order
domains,43–45 which may be due to the detrimental effects of
acute nicotine or that poor cognitive function acts as a risk
factor for the initiation of smoking. It has been suggested that
cognitive enhancement in SZ as a result of smoking might be
specific to the domains of working memory, attention, and
information processing.46,47 The cognitive‐enhancing effects
of smoking on neurocognitive performance in SZ have been
observed in both cross‐sectional (ie, smokers vs. non‐smokers)
and longitudinal studies (ie, smoking vs. abstinent conditions
and nicotine challenge paradigms) and span tasks associated
with sustained47–52 and selective attention,53 working memo-
ry,24,47,51,54,55 response inhibition,50 processing speed,49,50,54
prepulse inhibition,56–58 and sensorimotor gating.46,59,60
The high rates of smoking in BD and MDD are often
attributed to an attempt to self‐medicate affective symptoms2
and elevated monoamine oxidase (MAO)‐A levels associated
with the MDD.61–63 However, little is known about whether
smoking modulates cognition in BD or MDD. This is an
important issue given that MDD and BD are associated with
both high rates of smoking and poor cognitive performance. To
our knowledge, the only study to be conducted to date
demonstrated in a small sample of smokers and non‐smokers
with bipolar illness (I and II) that smoking status did not
significantly alter neuropsychological task performance on
measures of psychomotor speed, attention, memory, learning,
and executive function.64 Accordingly, in the present study, we
used a cross‐sectional design to evaluate the effects of smoking
status on neuropsychological task performance in subjects with
SZ, BD, and MDD.
METHODS
Participants
Smokers and non‐smokers with PDs were recruited from the
outpatient divisions of The Connecticut Mental Health Center
(CMHC, New Haven, CT) and its satellite clinics. Healthy
control smokers and non‐smoking controls between the ages of
18 and 65 were recruited from the Greater New Haven
community through flyers posted in the community and word‐
of‐mouth. Individuals who met any of the following criteria
were excluded from participation: (1) Full Scale IQ (FSIQ) of
<70 on a screening measure Shipley Full Scale Intelligence
Screen65; (2) history of a neurological illness/injury or previous
loss of consciousness; (3) abuse or dependence to alcohol or
any illicit substance within the past 3 months; or (4) inability to
provide written informed consent.
All patient participants had to meet Structured Clinical
Interview for DSM‐IV (SCID‐IV)66 criteria for one of the
Morisano et al.
following diagnoses: Schizophrenia/Schizoaffective Disorder
(SZ), Bipolar I Disorder (BD), or MDD. Further, they were
required to be in stable remission from active psychiatric
symptomatology, as judged by psychiatric evaluation, and
were without changes to psychiatric medication(s) for the past
3 months. Non‐psychiatric controls were excluded if under
current treatment with psychotropic medications, or if they
showed evidence of a current Axis I PD or substance abuse/
dependence on the SCID‐IV (except nicotine or caffeine
dependence). Smokers in the study were required to meet
DSM‐IV criteria for moderate to heavy nicotine dependence,
with a Fagerström Test for Nicotine Dependence (FTND)67
score of 5, expired breath carbon monoxide (CO) measure-
ment of >10 ppm, and an intake of 15 cigarettes per day, as
assessed via self‐reported 7‐day Timeline Follow Back.68 Non‐
smokers were either never‐smokers or those who had abstained
from cigarettes in the previous 6 months, and who had expired
breath CO levels of <10 ppm.
After eligibility determination, a total of 108 particip-
ants completed neurocognitive testing in a single session:
(1) SZ smokers (n ¼ 32), (2) SZ non‐smokers (n ¼ 15),
(3) BD smokers (n ¼ 10), (4) BD non‐smokers (n ¼ 6), (5)
MDD smokers (n ¼ 6), (6) MDD non‐smokers (n ¼ 10), (7)
control smokers (n ¼ 12), and (8) non‐smoking controls
(n ¼ 17). Written informed consent was obtained from all
participants seeking participation as approved by the Human
Investigation Committee at Yale University Medical School.
All participants were compensated for their participation.
Methods and Materials
All testing was completed at the Neurocognitive Laboratory
of the Program for Smokers with Mental Illness (PRISM) at the
Substance Abuse Center of CMHC. The initial screening
assessment included the following measures: demographics
questionnaire, SCID‐IV, FTND, urine toxicology screen to rule
out current substance use, CO measurement, Brief Psychiatric
Rating Scale (BPRS),69 Beck Depression Inventory‐2nd
Edition (BDI‐II),70 Positive and Negative Syndrome Scale
for Schizophrenia (PANSS)71 (used only with SZ participants),
and the Shipley Full Scale Intelligence Screen.65
Neuropsychological Assessment
Details of the neuropsychological battery used in the present
study were described previously.47,72 All tests were adminis-
tered according to standardized procedures and supervised by
the study neuropsychologist (KAS). The order of administra-
tion was randomly alternated in one of three pre‐assigned ways
in order to account for potential sequencing bias. Smokers were
given three prespecified smoke breaks during testing to ensure
that deprivation from cigarette smoking did not exceed
30 minutes47 and therefore minimize any neurocognitive
effects related to smoking withdrawal.
Digit Span: Forward and Backward. Digit span (5–
10 min) is a two‐part subtest of the Wechsler intelligence and
memory batteries that is used for measuring span of immediate
January–February 2013 47
verbal recall and aspects of working memory. It produces digits
forward, backward, and total scores.73
Conners’ Continuous Performance Test (CPT). The CPT‐
X (15 min) is designed to measure sustained attention and
response inhibition.74
Trail Making Test, Parts A and B (TMT). The TMT (5–
10 min) is administered in two parts: Part A, which primarily
measures psychomotor speed, requires participants to draw
lines connecting consecutively numbered circles; Part B is used
to assess cognitive set‐shifting (a type of executive function),
and requires participants to alternate connecting lines between
letters and numbers in a more complex sequence.75
Wisconsin Card Sorting Test (WCST). The WCST
(25 min) assesses aspects of executive functioning including
cognitive flexibility in response to feedback; it also involves
learning and memory, attention, and concentration. Commonly
reported outcomes are percent of total errors, number of
categories completed, and percent of perseverative errors.76
Visuospatial Working Memory (VSWM). The VSWM
(20 min) is a computerized delayed‐response spatial working
memory task, which assesses working memory for nonverbal
(object) visuospatial stimuli.24
California Verbal Learning Test—Second Edition (CVLT‐
II). The CVLT‐II (30 min) is a verbal learning and memory
test that measures encoding, immediate and delayed recall, and
recognition of new verbal information with the presentation of
a 16‐item list.77
Statistical Analyses
Group demographic characteristics were explored via a
series of ANOVAs and chi‐square analyses (see Table 1). The
diagnostic/smoking groups differed significantly on demo-
graphic characteristics (ie, age, years of education, and gender);
therefore, subsequent testing included these variables as
covariates. Although the groups also differed with regard to
distribution of race, the overwhelming majority of the sample
was Caucasian and the other races were too sparsely populated
across groups for race to be meaningfully included in subsequent
analyses. Consequently, race was dropped as a potential
covariate. Homogeneity of variance and normality of data
distributions were evaluated on all dependent variables. For
some outcome measures (noted as appropriate), due to the
distributional properties of the data, a natural‐logarithm
transformation was applied prior to testing.
A series of two‐way analyses of covariance (ANCOVAs)
were conducted to assess the interactive effects of diagnosis
(SZ, MDD, BD, or control) and smoking (smokers vs. non‐
smokers) on neurocognitive test scores. Three covariates
(age, gender, and years of education) were included in all
analyses. When significant ANCOVA effects were observed,
a series of Bonferroni‐adjusted pair‐wise comparisons were
48 Smoking Status and Cognition in Psychiatric Disorders
performed to investigate the nature of the significance.
Significance in all models was set at p < .05. Statistical
analyses were conducted using both the SAS System
(v. 9.1.3) and SPSS v. 15.0 for PC.
RESULTS
Demographic and Clinical Characteristics of
the Sample
Significant main effects of smoking status were observed
for sex, years of education and IQ, and main effects of
diagnosis were found on most baseline variables except CO
levels (p ¼ .08; Table 1).
Comparison of Neuropsychological Performance
across Diagnoses and Smoking Status
CVLT‐II
A significant main effect of diagnosis was found across all
outcomes (Total, Trial 1, Trial 5, List B, short‐term free recall
[STFR], short‐term cued recall [STCR], long‐term free recall
[LTFR], long‐term cued recall [LTCR], and recognition/
discriminability [R/D]). There were also significant interaction
effects of diagnosis by smoking status on List B, LTCR, and
R/D scores, and trends towards an interaction effect on STCR
(Table 2).
Bonferroni‐adjusted pair‐wise comparisons were conducted
to analyze specific group differences on all significant
outcomes. Individuals with SZ scored significantly lower
than non‐psychiatric controls on CVLT Total (p < .01), Trial 1
(p < .05), Trial 5 (p < .05), STFR (p < .0001), STCR
(p < .0001), LTFR (p < .0001), and LTCR (p < .0001); while
BD and MDD participants did not differ significantly from
non‐psychiatric controls on any of these outcomes (p ¼ 1.0 in
all cases). Adjusted pair‐wise comparisons on List B scores
revealed that none of the PD groups differed significantly from
controls (SZ: p ¼ .58, BD: p ¼ .96, MDD: p ¼ 1.0). Within
the control group, however, smokers had significantly lower
List B scores than non‐smokers (p < .05); no effect of smoking
status was found within the SZ (p ¼ 1.0), BD (p ¼ .42), or
MDD (p ¼ 1.0) groups. On LTCR, among individuals with
SZ, scores were significantly higher among smokers versus
non‐smokers (p < .05). This was not the case in the other
diagnostic groups, where no smoking effect was observed
(BD: p ¼ .70, controls: p ¼ 1.0, MDD: p ¼ .37). On R/D
scores, adjusted comparisons revealed that none of the PD
groups differed significantly from controls (p ¼ .19, p ¼ 1.0,
p ¼ 1.0, respectively), although among individuals with SZ,
smokers scored significantly higher than non‐smokers (p < .01).
This was not the case within the other diagnostic groups, where
no difference was found between smokers and non‐smokers
(BD: p ¼ 1.0, controls, p ¼ .52, MDD: p ¼ 1.0).
CPT
No evidence of a smoking or diagnosis by smoking effect
was found within any of the CPT tests. A significant diagnosis
effect was found in the CPT variability analysis, but all
January–February 2013
 TABLE 1. Participant demographics and clinical characteristics by subgroup

Main
effect of
Control Control SZ SZ BD BD MDD MDD smoking Main
smokers non‐smokers smokers non‐smokers smokers non‐smokers smokers non‐smokers status* effect of
(n ¼ 12) (n ¼ 17) (n ¼ 32) (n ¼ 15) (n ¼ 10) (n ¼ 6) (n ¼ 6) (n ¼ 10) (p) diagnosis (p)*
Age M (SD) 38.0 (9.3) 38.5 (15.3) 41.3 (6.9) 39.9 (9.2) 46.9 (7.2) 41.3 (13.3) 44.8 (5.1) 46.9 (10.7) .648 <.05
Sex (% male) 83.3 (10) 70.6 (12) 81.3 (26) 53.3 (8) 60.0 (6) 0.0 (0) 33.3 (2) 50.0 (5) <.05 <.05
Race
Caucasian 10 14 15 9 10 5 5 10 .27

Morisano et al.
<.0001
African American 2 3 16 6 0 0 1 0
Hispanic 0 0 1 0 0 1 0 0
Years of education 13.5 (2.7) 15.9 (2.4) 11.6 (2.4) 13.4 (2.4) 13.4 (2.0) 15.7 (2.3) 13.3 (1.8) 15.0 (3.3) <.001 <.001
Estimated FSIQ 97.5 (11.7) 111.4 (13.4) 88.4 (11.0) 90.7 (11.2) 103.5 (10.5) 106.0 (8.4) 100.8 (11.9) 108.3 (9.3) <.01 <.001
# Cigs per day 21.1 (8.3) 0 23.7 (10.9) 0 21.4 (8.7) 0 15.8 (12.5) 0 – <.05
Baseline carbon 20.4 (5.2) 1.0 (.6) 24.8 (14.7) 1.1 (.7) 16.5 (6.1) 5 (.5) 20.8 (13.5) 1.2 (.6) – .08
monoxide
level (ppm)
FTND 6.1 (1.2) .0 (.0) 6.8 (1.6) .0 (.0) 6.7 (1.8) .0 (.0) 7.2 (1.2) .0 (.0) – <.05

January–February 2013
BDI 3.9 (5.8) 1.3 (1.4) 9.9 (9.5) 7.0 (6.0) 12.6 (6.9) 10.2 (11.7) 17.8 (9.0) 13.7 (9.2) .07 <.001
BPRS 17.1 (8.7) 19.1 (1.8) 35.4 (6.8) 38.9 (5.0) 24.9 (3.2) 30.0 (1.9) 28.6 (4.2) 27.3 (6.7) .53 <.001
PANSS positive – – 13.7 (3.7) 15.3 (2.2) – – – – .13 –
PANSS negative – – 14.9 (3.2) 14.3 (2.7) – – – – .54 –
PANSS general – – 28.8 (5.5) 30.5 (4.3) – – – – .32 –
PANSS total – – 57.2 (10.5) 60.1 (8.4) – – – – .36 –
*
ANOVA results are reported for continuous variables, Chi‐square results are reported for categorical variables.
SZ ¼ Schizophrenia; BD ¼ Bipolar Disorder; MDD ¼ Major Depressive Disorder; FTND ¼ Fagerstrom Test for Nicotine Dependence; BDI ¼ Beck Depression Inventory; PANSS ¼ Positive and Negative
Symptoms Scale for Schizophrenia.

49
50
TABLE 2. Neurocognitive outcomes across subgroups
Diagnosis Main Main
Control Control SZ SZ BD BD MDD MDD X smoking effect of effect of
smokers non‐smokers smokers non‐smokers smokers non‐smokers smokers non‐smokers interaction* smoking status* diagnosis*

CPT, hit rate (%)† n ¼ 12, 98.5 (1.1) n ¼ 17, 98.6 (1.8) n ¼ 31, 97.8 (2.7) n ¼ 15, 97.2 (3.7) n ¼ 10, 98.8 (.95) n ¼ 6, 98.7 (1.6) n ¼ 6, 99.0 (.49) n ¼ 10, 98.8 (1.7) F(3,96) ¼ .08, p ¼ .97 F(1,96) ¼ .97, p ¼ .97 F(3,96) ¼ 1.69, p ¼ .33
CPT, omissions† n ¼ 12, 1.5 (1.1) n ¼ 17, 1.4 (1.8) n ¼ 31, 2.2 (2.7) n ¼ 15, 2.8 (3.8) n ¼ 10, 1.2 (1.0) n ¼ 6, 1.3 (1.6) n ¼ 6, 1.0 (.49) n ¼ 10, 1.2 (1.7) F(3,96) ¼ .14, p ¼ .94 F(1,96) ¼ .28, p ¼ .60 F(3,96) ¼ 2.13, p ¼ .10
CPT, comissions† n ¼ 12, 37.3 (19.9) n ¼ 17, 21.6 (20.1) n ¼ 31, 33.4 (22.8) n ¼ 15, 28.7 (20.6) n ¼ 10, 24.4 (12.6) n ¼ 6, 44.5 (14.9) n ¼ 6, 21.0 (10.1) n ¼ 10, 25.6 (11.7) F(3,96) ¼ 2.63, p ¼ .06 F(1,96) ¼ .01, p ¼ .92 F(3,96) ¼ .39, p ¼ .76
CPT, variability† n ¼ 12, 8.4 (3.9) n ¼ 17, 9.4 (8.5) n ¼ 31, 13.5 (8.7) n ¼ 15, 15.4 (9.1) n ¼ 10, 8.6 (5.5) n ¼ 6, 9.7 (3.0) n ¼ 6, 13.9 (16.7) n ¼ 10, 7.6 (4.1) F(3,96) ¼ .18, p ¼ .91 F(1,96) ¼ .08, p ¼ .78 F(3,96) ¼ 3.46, p < .05
CPT, D′ n ¼ 12, 2.6 (.8) n ¼ 17, 3.8 (2.1) n ¼ 31, 2.7 (1.4) n ¼ 15, 2.6 (1.0) n ¼ 10, 2.9 (1.0) n ¼ 6, 2.1 (.79) n ¼ 6, 2.8 (1.1) n ¼ 10, 2.9 (.79) F(3,96) ¼ 1.95, p ¼ .13 F(1,96) ¼ .18, p ¼ .67 F(3,96) ¼ .58, p ¼ .63
VSWM, 30‐second n ¼ 12, 1.3 (.6) n ¼ 17, 1.1 (.5) n ¼ 32, 1.9 (.9) n ¼ 14, 2.6 (1.6) n ¼ 10, 1.6 (.7) n ¼ 6, 2.2 (2.1) n ¼ 6, 1.0 (.3) n ¼ 10, 1.5 (1.3) F(3,96) ¼ .69, p ¼ .56 F(1,96) ¼ 2.01, p ¼ .16 F(3,96) ¼ 5.36, p < .01
delay (cm)
VSWM, 60‐second n ¼ 12, 1.4 (.7) n ¼ 17, 1.0 (.6) n ¼ 32, 2.2 (1.2) n ¼ 14, 2.3 (1.7) n ¼ 10, 1.8 (.8) n ¼ 6, 2.6 (1.7) n ¼ 6, 1.3 (.6) n ¼ 10, 1.5 (.8) F(3,96) ¼ 1.30, p ¼ .28 F(1,96) ¼ .39, p ¼ .53 F(3,96) ¼ 4.97, p < .01
delay (cm)
WCST, % errors† n ¼ 12, 27.9 (16.7) n ¼ 15, 18.6 (13.1) n ¼ 32, 32.2 (17.3) n ¼ 15, 37.0 (21.3) n ¼ 10, 30.0 (19.8) n ¼ 6, 36.2 (13.2) n ¼ 6, 21.7 (15.1) n ¼ 10, 17.1 (6.1) F(3,95) ¼ 1.99, p ¼ .12 F(1,95) ¼ .81, p ¼ .37 F(3,95) ¼ 4.57, p < .01
WCST, % perseverative n ¼ 12, 12.6 (6.8) n ¼ 14, 9.3 (5.3) n ¼ 32, 14.6 (8.9) n ¼ 15, 22.3 (15.9) n ¼ 10, 20.4 (17.8) n ¼ 6, 15.3 (6.5) n ¼ 6, 11.8 (10.6) n ¼ 10, 9.0 (3.7) F(3,94) ¼ 1.58, p ¼ .20 F(1,94) ¼ .46, p ¼ .50 F(3,94) ¼ 3.55, p < .05
errors†
WCST, categories completed‡ n ¼ 12, 4.5 (2.1) n ¼ 14, 5.7 (1.1) n ¼ 32, 3.8 (2.2) n ¼ 15, 3.3 (2.6) n ¼ 10, 5.0 (2.2) n ¼ 6, 4.2 (2.1) n ¼ 6, 4.5 (2.3) n ¼ 10, 5.9 (.3)
x2(3, n ¼ 105) ¼ 7.68, x2(1, n ¼ 105) ¼ .89, x2(3, n ¼ 105) ¼ 3.84,
p ¼ .0531 p ¼ .35 p ¼ .28
TMT Part A (scaled score) n ¼ 12, 11.7 (2.1) n ¼ 17, 10.7 (3.3) n ¼ 30, 8.2 (3.1) n ¼ 15, 8.7 (2.8) n ¼ 10, 10.0 (2.4) n ¼ 6, 8.2 (3.2) n ¼ 6, 11.5 (1.4) n ¼ 10, 10.5 (2.5) F(3,94) ¼ .99, p ¼ .40 F(1,94) ¼ 4.56, p < .05 F(3,94) ¼ 4.97, p < .01
TMT Part B (scaled score) n ¼ 12, 11.1 (2.2) n ¼ 17, 11.9 (3.5) n ¼ 30, 7.8 (2.9) n ¼ 14, 8.3 (2.6) n ¼ 10, 9.6 (1.9) n ¼ 6, 8.0 (3.0) n ¼ 6, 10.5 (2.9) n ¼ 10, 11.8 (3.9) F(3,93) ¼ 1.50, p ¼ .22 F(1,93) ¼ .53, p ¼ .47 F(3,93) ¼ 7.01, p < .001
CVLT, total score n ¼ 12, 50.8 (11.6) n ¼ 16, 43.7 (9.8) n ¼ 31, 36.1 (11.1) n ¼ 15, 34.9 (8.9) n ¼ 10, 47.9 (11.3) n ¼ 6, 41.5 (7.2) n ¼ 6, 43.0 (17.4) n ¼ 10, 49.8 (10.2) F(3,95) ¼ 1.79, p ¼ .15 F(1,95) < .01, p ¼ .98 F(3,95) ¼ 5.46, p < .01
CVLT, Trial 1 n ¼ 12, 5.3 (2.0) n ¼ 16, 6.6 (1.7) n ¼ 32, 4.7 (1.6) n ¼ 15, 3.8 (1.2) n ¼ 10, 5.7 (2.0) n ¼ 6, 4.8 (1.3) n ¼ 6, 6.0 (1.7) n ¼ 10, 6.2 (2.3) F(3,96) ¼ 2.32, p ¼ .08 F(1,96) ¼ .83, p ¼ .36 F(3,96) ¼ 4.83, p < .01
CVLT, Trial 5 n ¼ 12, 10.8 (1.9) n ¼ 16, 12.9 (2.7) n ¼ 32, 9.0 (3.2) n ¼ 15, 8.9 (2.7) n ¼ 10, 11.4 (2.2) n ¼ 6, 10.3 (2.7) n ¼ 6, 9.7 (5.5) n ¼ 10, 11.7 (2.8) F(3,96) ¼ 1.47, p ¼ .23 F(1,96) ¼ .18, p ¼ .67 F(3,96) ¼ 3.47, p < .05
CVLT, List B n ¼ 12, 4.1 (2.1) n ¼ 16, 6.2 (1.4) n ¼ 32, 3.8 (1.7) n ¼ 15, 4.5 (2.4) n ¼ 10, 4.7 (1.3) n ¼ 6, 3.7 (1.2) n ¼ 6, 5.5 (1.2) n ¼ 10, 5.7 (1.5) F(3,96) ¼ 3.20, p < .05 F(1,96) ¼ .33, p ¼ .57 F(3,96) ¼ 3.22, p < .05
CVLT, short‐term free recall n ¼ 12, 9.2 (2.1) n ¼ 16, 10.8 (3.4) n ¼ 32, 6.6 (2.6) n ¼ 15, 5.9 (3.2) n ¼ 10, 9.7 (2.2) n ¼ 6, 9.0 (3.1) n ¼ 6, 8.2 (3.6) n ¼ 10, 10.0 (2.7) F(3,96) ¼ 1.43, p ¼ .24 F(1,96) ¼ .30, p ¼ .58 F(3,96) ¼ 9.20, p < .0001
CVLT, short‐term cued recall n ¼ 12, 10.6 (1.1) n ¼ 16, 11.8 (2.3) n ¼ 32, 8.3 (2.8) n ¼ 15, 6.3 (3.4) n ¼ 10, 10.7 (2.1) n ¼ 6, 10.8 (2.1) n ¼ 6, 10.0 (3.3) n ¼ 10, 11.8 (2.0) F(3,96) ¼ 2.61, p ¼ .06 F(1,96) ¼ .27, p ¼ .61 F(3,96) ¼ 14.25, p < .0001
CVLT, long‐term free recall n ¼ 12, 9.3 (1.9) n ¼ 15, 11.0 (3.2) n ¼ 32, 6.7 (3.0) n ¼ 15, 5.4 (3.7) n ¼ 10, 10.3 (2.4) n ¼ 6, 9.7 (2.3) n ¼ 6, 8.8 (4.2) n ¼ 10, 10.7 (3.1) F(3,95) ¼ 1.74, p ¼ .16 F(1,95) ¼ .02, p ¼ .88 F(3,95) ¼ 9.77, p < .0001
CVLT, long‐term cued recall n ¼ 12, 10.3 (1.2) n ¼ 15, 11.5 (2.6) n ¼ 32, 8.3 (2.7) n ¼ 15, 6.1 (3.5) n ¼ 10, 11.9 (1.9) n ¼ 6, 10.2 (2.7) n ¼ 6, 9.3 (4.0) n ¼ 10, 12.1 (2.3) F(3,95) ¼ 3.79, p < .05 F(1,95) ¼ .21, p ¼ .65 F(3,95) ¼ 10.91, p < .0001
CVLT recognition/ n ¼ 12, 12.1 (3.7) n ¼ 15, 13.9 (2.0) n ¼ 32, 13.6 (1.8) n ¼ 15, 11.2 (3.4) n ¼ 10, 13.8 (1.9) n ¼ 6, 13.0 (2.0) n ¼ 6, 14.5 (1.4) n ¼ 10, 15.2 (1.2) F(3,95) ¼ 4.27, p < .01 F(1,95) ¼ .59, p ¼ .44 F(3,95) ¼ 2.73, p < .05
discriminability

*
ANCOVA results (covariates: age, gender, and years of education); †Due to the distributional properties of the data, a natural‐logarithm transformation was applied to the outcome measure prior to testing; ‡Over
50% of the subjects had completed all six categories. This variable was dichotomized as <6 (41%) versus 6 (58%) and a logistic regression analysis was performed instead of an ANCOVA.
SZ ¼ Schizophrenia; BD ¼ Bipolar Disorder; MDD ¼ Major Depressive Disorder; CPT ¼ Continuous Performance Test; VSWM ¼ Visuospatial Working Memory; WCST ¼ Wisconsin Card Sorting Test;
TMT ¼ Trial Making Test; CVLT ¼ California Verbal Learning Test.
TMT
WCST

VSWM

Smoking Status and Cognition in Psychiatric Disorders

Digit Span
was applied.

DISCUSSION
years of education.

MDD: p ¼ 1.0) tasks.

inversely associated with age.

January–February 2013
forward or backward performance (data not shown).

The current study was a preliminary cross‐sectional

(p < .05, but this pattern did not differ across diagnostic
significantly higher for smokers than for non‐smokers
(see Table 2). Bonferroni‐adjusted pair‐wise comparisons

investigation of the effects of cigarette smoking on neuro-

We found no significant effects of diagnosis, smoking
participants did not differ from controls on the 30‐second delay
indicated that individuals with SZ scored significantly higher
diagnosis effect was found within % Errors and % Persevera-
No evidence of a smoking or diagnosis by smoking

(p ¼ 1.0 in both cases) or 60‐second delay (BD: p ¼ .06,

second delay (p < .05) tasks. In contrast, BD and MDD
indicated that individuals with SZ scored significantly lower

VSWM), while participants with BD or MDD did not differ

cognitive function across several psychiatric diagnoses.
than controls on both the 30‐second delay (p < .05) and 60‐
VSWM tests. Bonferroni‐adjusted pair‐wise comparisons
groups, p ¼ .25). Overall, Parts A and B scaled scores were
(BD: p ¼ .08, MDD: p ¼ 1.0). Part A scaled scores were
contrast, BD and MDD participants did not differ from
for both parts, and a smoking effect was found within Part A
either Part A or B, a significant diagnosis main effect was found
p ¼ 1.0), although overall scores on both outcomes were
Perseverative Errors (BD: p ¼ 1.0, MDD: p ¼ .65; SZ:

Participants with SZ performed significantly worse than

than controls on both Part A (p < .5) and Part B (p < .01). In
Errors (BD: p ¼ 1.0, MDD: p ¼ .6; SZ: p ¼ 1.0) or on %
PD groups differed significantly from controls on either %
wise comparisons revealed, however, that none of the
tive Errors (see Table 2). Bonferroni‐adjusted pair‐
effect was found within any of the WCST tests. A significant
pair‐wise comparisons across diagnostic categories failed to

A significant diagnosis main effect was found on both

positively associated with age and negatively associated with

controls on several neurocognitive tests (CVLT‐II, TMT, and

status, or a diagnosis  smoking interaction for digit span
controls on Part A (BD: p ¼ .33, MDD: p ¼ 1.0) or Part B
Although no smoking by diagnosis effect was found on
achieve statistical significance once a Bonferroni adjustment
significantly from controls on any task; these findings are
consistent with the literature reporting more profound neuro-
cognitive deficits in SZ than in BD and MDD.32,33
With regard to interactions of smoking status and diagnosis,
there was an association between better performances on three
CVLT‐II tasks (STCR and LTCR, recognition/discriminabili-
ty) and the presence of smoking in individuals with SZ, after
co‐varying for group differences in age, gender, and years of
education. Better performance was observed in smokers with
SZ when asked to recall verbal information after either a short
or long delay with the benefit of semantic prompting (STCR
and LTCR), and in recognizing previously presented verbal
information when given a forced‐choice (CVLT‐II recogni-
tion). Furthermore, in the non‐psychiatric control group, there
was an association between being a smoker and worse
performance on a CVLT‐II task that measured the effects of
proactive interference (List B). Interestingly, smoking status
was not associated with altered cognitive performance in
patients with BD or MDD. Given the small size of the smoking
status MDD and BD sub‐groups these findings should be
interpreted with caution. Nevertheless, our finding of a lack of
an effect of BD subjects is similar to the results of Law et al.64
There is no preexisting literature on the effects of smoking on
neurocognitive performance in MDD with which to contrast
the current results.
It is notable that we did not observe effects of smoking on
tasks that have previously been shown to be sensitive to
tobacco effects, such as attention and spatial working memory
reported in previous cross‐sectional studies comparing
smokers and non‐smokers with SZ.24,50,53 Methodological,
statistical, and population differences between this and other
studies may explain these discrepancies. Nonetheless, our
results suggest a degree of specificity in cigarette‐smoking
modulation of neurocognitive deficits in individuals with SZ
compared to BD and MDD. If confirmed, these findings could
have significant treatment implications for smokers with co‐
morbid PDs who wish to quit. Targeting cognitive deficits has
been proposed as a promising avenue for smoking cessation
treatment in SZ,40,78,79 however, our findings suggest this may
not be an appropriate strategy for BD and MDD smokers, and
therefore other treatment approaches should be explored.
Limitations of this study included: (1) secondary analysis of
data derived from three studies on cognition in persons with
SZ, BD, and major depression versus controls conducted over a
5‐year period; (2) power to detect differences between smoking
and non‐smoking BD and MDD groups were limited by the
small samples sizes of these subgroups (in some cases with N’s
<10 subjects in the BD and MDD subgroups); and (3) cross‐
sectional design of the study insofar as comparison of smoking
status effects. That the psychiatric groups were on psychotropic
medications which could impact cognitive function could be
considered a limitation, nevertheless, this is likely to be the
most clinically relevant situation for these populations and is
therefore important to study. Further studies are needed to
evaluate the effects of cigarette smoking on cognitive
performance in these affective disorders. These should include
Morisano et al.
larger sample sizes, incorporate longitudinal designs (to
evaluate the effects of smoking abstinence and reinstatement
on cognition47), and evaluate the association between
cognition and smoking cessation treatment outcomes (associ-
ation between baseline cognitive performance on quit rates in
BD and MDD78,79). Another potential avenue of research is to
examine the effects of smoking history (ie, current, former, and
never smokers) in BD and MDD as recent studies in SZ have
identified subtle differences between former and never smokers
which may be masked by grouping subjects together as non‐
smokers.50,80
In conclusion, the results of this preliminary study suggest
that the improved cognitive abilities associated with cigarette
smoking are specific to SZ, such that smoking status does not
alter cognitive performance in BD and MDD.
This work was supported in part by Grants K02‐DA‐16611,
R01‐DA‐13672, and R01‐DA‐14039 from the National
Institutes on Drug Abuse, Bethesda, MD (Dr. George); an
NARSAD Independent Investigator Award (Dr. George); an
operating grant (MOP#115145) from the Canadian Institutes
of Health Research (Dr. George); the Endowed Chair in
Addiction Psychiatry at the University of Toronto (Dr. George);
an NARSAD Young Investigator Award (Dr. Sacco); and
Centre for Addiction and Mental Health Foundation Research
Fellowships (Drs. Morisano and Wing).
We thank Angelo Termine, Jennifer Vessicchio, LCSW,
Melissa Dudas, Aisha Seyal, Taryn Allen, Erin Reutenauer, and
Marc Potenza, MD, PhD for their assistance with study
procedures.
Declaration of Interest
Drs. Morisano, Sacco, and Wing, and Ms. Arenovich have
no conflicts to report. Dr. George reports that he has received
grant support from Pfizer, Inc., and has received consulting fees
from Pfizer, Evotec, Eli Lilly, Janssen‐Ortho, Astra‐Zeneca,
and Novartis in the past 2 years. The authors alone are
responsible for the content and writing of this paper.
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