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1. Original article
A case-comparison study of executive functions in alcohol-dependent
adults with maternal history of alcoholism
Olivier Cottencin a,*, Jean-Louis Nandrino b
, Laurent Karila c
, Caroline Mezerette a
, Thierry Danel a
a
Department of Addictology, University of Lille 2, Faculty of Medicine, University Hospital of Lille, 57 Bd de Metz, 59037 Lille Cedex, France
b
Department of Psychology, URECA EA 1059, University of Lille 3, France
c
Department of Addictology, University Hospital Paul Brousse, Villejuif, France
Received 9 July 2008; received in revised form 4 December 2008; accepted 10 December 2008
Available online 4 February 2009
Abstract
Introduction. e As executive dysfunctions frequently accompany alcohol dependence, we suggest that reports of executive dysfunction in
alcoholics are actually due, in some case to a maternal history of alcohol misuse (MHAþ). A history of maternal alcohol dependence increases
the risk for prenatal alcohol exposure to unborn children. These exposures likely contribute to executive dysfunction in adult alcoholics. To
assess this problem, we propose a case-comparison study of alcohol-dependent subjects with and without a MHA.
Methods. e Ten alcohol-dependent subjects, with a maternal history of alcoholism (MHA) and paternal history of alcoholism (PHA), were
matched with 10 alcohol-dependent people with only a paternal history of alcoholism (PHA). Executive functions (cancellation, Stroop, and
trail-making A and B tests) and the presence of a history of three mental disorders (attention deficit hyperactivity disorder, violent behavior while
intoxicated, and suicidal behavior) were evaluated in both populations.
Results. e Alcohol-dependent subjects with MHA showed a significant alteration in executive functions and significantly more disorders
related to these functions than PHA subjects. The major measures of executive functioning deficit are duration on task accomplishment in all
tests. Rates of ADHD and suicidality were found to be higher in MHA patients compared to the controls.
Conclusion. e A history of MHA, because of the high risk of PAE (in spite of the potential confounding factors such as environment) must
be scrupulously documented when evaluating mental and cognitive disorders in a general population of alcoholics to ensure a better identifi-
cation of these disorders. It would be helpful to replicate the study with more subjects.
Ó 2009 Elsevier Masson SAS. All rights reserved.
Keywords: Alcohol dependence; Maternal history of alcoholism; Prenatal alcohol exposure; Executive function disorders
1. Introduction
Empirical studies have surprisingly shown that, drinking
practice and duration are relatively weak predictors of neuro-
psychological impairments in abstinent alcoholics, but that
neuropsychological morbidity is rather related to age [19,42],
high-density alcoholism families (multigenerational history of
alcoholism) [15], early onset of alcohol consumption [37] and
childhood hyperactivity [52]. In addition, structural brain
changes have been suggested as a possible substrate underlying
cognitive impairments (basal ganglia, corpus callosum, cere-
bellum, and hippocampus) [30]. Neuroimaging, neuropatho-
logical studies [35,40], and examination of event-related
potentials [21] suggest that the frontal brain systems are espe-
cially susceptible to alcoholism-related damage. This frontal
lobe damage is manifested clinically as alterations of executive
functions [22,30]. While certain cognitive functions such as
psychomotor performance and short-term memory [11], verbal
recall and visuospatial ability [48] can improve or return to
normal levels after abstinence, executive function impairments
do persist [8,36,53], even after long periods of abstinence [34].
On the other hand, numerous studies also suggest that
executive functions are impaired in people with prenatal
* Corresponding author. Tel.: þ33 3 20 44 58 38; fax: þ33 3 20 44 54 37.
E-mail address: ocottencin@chru-lille.fr (O. Cottencin).
0924-9338/$ - see front matter Ó 2009 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.eurpsy.2008.12.003
Available online at
www.sciencedirect.com
European Psychiatry 24 (2009) 195e200

2. alcohol exposure (PAE), even when the mothers drank only
moderately during pregnancy [26,29]. This disorder is now
known to persist throughout the offspring’s life and can cause
permanent changes in the brain including reduced brain size,
alterations of tissue density, volumetric reductions and
abnormalities in the cerebellum, basal ganglia and corpus
callosum [10]. Besides alterations in brain structure, individ-
uals with histories of prenatal alcohol exposure face long-
lasting deficits that affect many aspects of cognitive and
behavioral functioning. Different domains of executive func-
tions are impaired in these children: cognitive flexibility,
response inhibition, planning and concept formation [29]. In
addition, children with PAE when compared with non exposed
children displayed deficits in both verbal and non verbal
fluency [43], in complex tasks (progressive planning test,
Lhermitte memory tasks, grooved pegboard test) [5], and in
concept formation and conceptual set shifting [33]. Similarly
PAE adolescents have substantial impairments in their abilities
to solve problems in their everyday life, even in the absence of
mental retardation [32].
Since it is known that PAE is a crucial risk factor for the
development of alcohol-related disorders (14.1% versus
4.5%), persons with PAE are undoubtedly overrepresented in
the general population of alcoholics (about 64%) (with a birth
prevalence of PAE within a range of 0.2e2.0 per 1000 live
births in the general population) according to the methods
used across a variety of populations [6,20,31,46].
It is thus possible that reports of executive dysfunction in
adult alcoholics are actually due, at least in some cases, to
PAE. That is, PAE may be a confounding factor in the
assessment of executive dysfunction in alcoholics. Identifying
the nature and severity of cognitive impairment should inform
the choice and timing of treatment strategies (i.e. deficits in
problem solving skills and adaptive functioning have impli-
cations for patient’s compliance and therapeutic interventions
in this population).
To assess this problem we compared two samples of alcohol-
dependent subjects, matched for age, educational level and
length of alcohol exposure. All patients had a paternal history of
alcoholism (PHAþ) in order to control for the effects of familial
alcoholism on child development. Therefore we separated those
patients with a paternal history of alcoholism in two groups:
a group with a maternal history of alcoholism (high probability
of PAE) (MHAþ) and another group without a maternal history
of alcoholism (MHA). We assessed executive function
performance in two ways: (1) we conducted neuropsychological
tests utilizing the cancellation, Stroop colors and trail-making
tests (parts A and B) and (2) we examined the subjects’ history
for disorders in which executive dysfunctions are suspected.
One common disorder involving executive dysfunction is
attention-deficit hyperactivity disorder (ADHD), which is now
viewed as a neurologically-based condition with primary defi-
cits in executive functions [27,41]. Because of the association
between focal prefrontal damage and an impulsive subtype of
aggressive behavior [12], we also looked for violent actions,
towards oneself (attempted suicide) or others while under the
effect of alcohol.
2. Subjects and methods
2.1. Study population
The study was performed on consecutive inpatients exam-
ined at the Department of Addictology of the University
Hospital of Lille (France). All subjects gave their informed
consent to participate in the study. We recruited 10 patients
(men and women) who met the DSM IV criteria for alcohol
dependence [4] and who had a paternal and a maternal history
of alcoholism. The semi-structured interview asked about
educational level, duration of consumption, living conditions
during childhood and parental history of alcoholism. The
probability of PAE was considered very high and the subjects
were considered exposed to alcohol in utero if they described
their mother as meeting any one of the following criteria: (a)
regular consumer of alcohol, (b) treated for an alcohol-related
disorder, (c) had alcohol-related health problems, (d) died
from a disease associated with alcohol consumption, (e) had
social, family, legal or occupational difficulties secondary to
alcohol consumption, (f) had alcohol-related disorders,
according to close contacts, or (g) had children placed in care
because of alcohol consumption. At the time of the evaluation,
subjects had abstained from alcoholic beverages for at least 8
days and were not taking psychotropic drugs (including
medication). Patients with a history of head injury with loss of
consciousness were excluded from the study.
Of the 10 patients who met the DSM IV diagnostic criteria
for alcohol dependence and have a high probability of PAE, 8
were men and 2 women; their mean age was 37.5 years (sd
6.7), and the mean duration of the alcohol disorders 8.3 years
(sd 8). The semi-structured interview found that the mothers of
all 10 patients were known to have regularly consumed
alcohol and that information was also confirmed by other close
family or friends. Seven mothers had been treated for an
alcohol-related disorder, 7 had alcohol-related health prob-
lems, 4 had died from a disease associated with alcohol
consumption, 1 had secondary social problems related to
alcohol consumption, 8 had family problems, and 1 had legal
difficulties. Five of these individuals had children placed in
care because of their alcohol consumption.
Individuals were evaluated using the Institute Of Medicine
criteria for FAS [45] and did not present with FAS. They did
not receive any type of early intervention.
2.2. Control population
We examined 185 case records (from our Department of
Addictology) to identify control subjects matched with the
study subjects for age, sex, educational level, duration of
consumption, living conditions during childhood, and paternal
history of alcoholism (PHAþ) but whose mothers had no
history of drinking (matching is detailed in Table 1). The
control sample thus consisted of 10 patients who met the DSM
IV criteria for alcohol dependence and who were not subject to
PAE. All subjects in the study had a history of paternal
196 O. Cottencin et al. / European Psychiatry 24 (2009) 195e200

3. alcoholism in order to control for the effects on families from
high-density alcoholism [15].
2.3. Evaluation of executive functions
Several domains of executive functioning were evaluated
(selective attention, inhibition and cognitive flexibility).
A cancellation (cross-out) task in which patients are presented
with a sheet containing several lines and asked to draw over all
of them with a pencil mark, studied selective attentional
capacity [28].
Inhibition capacities were studied with the Stroop colors
test: a test of reading fluency and mental flexibility which
requires subjects to read lists of words and colors. The subject
must first read the names of colors printed in black, then the
subject must identify the color of printed X’s, and finally, the
subject must name the color of each printed word [47].
Finally cognitive flexibility was studied with the trail-
making tests, parts A and B which require visuomotor tracking
(the subject, as quickly as possible, connects numbers and
letters in numerical order that are scattered on a page) [24].
2.4. Disorders potentially related to executive function
Attention-deficit hyperactivity disorder (ADHD) was
diagnosed retrospectively with the 11-item Tarter question-
naire [49]. Eight positive responses are required for a retro-
spective diagnosis. Tarter questionnaire is a retrospective
self-report checklist that assesses for impulsive behavior,
hyperactivity, attentional problems, social interaction, and
acquisition of language skills prior to the age of 13 years.
Suicide risk was assessed with the MINI-DSM IV criteria
[44], and questions during the interview explored a history of
intoxication with violence.
Data were collected prospectively, at the same visit.
2.5. Statistical analysis
2.5.1. Power calculation
Assuming the hypothesis of a frequency of 60% of PAE
in the alcoholic population, and a frequency of 6% of
alcohol dependence, we needed 26 patients to include (95%;
a ¼ 5%). Data were normally distributed and the statistical
analysis in this study used a computerized version of the
Wilcoxon test for paired series in SAS V8.1 software (SAS
Institute, Cary, NC, USA) because of the small size of our
sample. Results were considered significant if the p value
was less than 0.05.
Table 1
Matching of alcohol-dependent populations: one exposed prenatally to alcohol and the other not exposed. ‘‘Child protective services’’ means that the patient or
control benefitted of an in-home placement during childhood.
Sex Age Age at the end of schooling Duration of alcoholism Alcoholism in father Alcoholism in mother Child protective services
Patient M 48 13 25 þ þ Yes
Control M 53 14 28 þ
Patient M 46 16 20 þ þ No
Control M 46 16 17 þ
Patient M 38 16 6 þ þ Yes
Control M 36 16 8 þ
Patient M 34 20 4 þ þ Yes
Control M 37 18 5 þ
Patient F 43 14 11 þ þ No
Control F 41 14 13 þ
Patient F 33 15 4 þ þ No
Control F 32 16 4 þ
Patient M 29 19 1 þ þ Yes
Control M 26 18 2 þ
Patient M 41 16 5 þ þ Yes
Control M 39 17 7 þ
Patient M 27 16 2 þ þ No
Control M 28 16 1 þ
Patient M 34 15 5 þ þ No
Control M 34 14 4 þ
60
+/-9
130
+/-32
84
+/-42
95
+/-21
128
+/-28
39
+/-8
87
+/-23
51
+/-8,5
86
+/-28
54
+/-19
0
20
40
60
80
100
120
140
160
Cancelling Stroop 1
(Verbal)
Stroop 2
(Color)
Trail A Trail B
Neuropsychological Tests
performance
duration
MHA+
MHA-
Fig. 1. Neuropsychological assessment of patients with or without maternal
exposure to alcohol (MHAþ and MHA).
197
O. Cottencin et al. / European Psychiatry 24 (2009) 195e200

4. 3. Results
3.1. Executive function disorders (Fig. 1)
All control subjects with PHAþ performed the cancellation
test without error in a time of 45 s or less. Nine of the subjects
with MHAþ took more than 50 s to complete the test, and five
made errors. The paired Wilcoxon test showed a significant
difference in the time required for the test ( p ¼ 0.0039) but not
in the number of errors ( p ¼ 0.0625).
All control subjects and 7 subjects with MHAþ could
perform the Stroop test, but 3 study subjects could not
concentrate, became very irritable and refused to continue.
The paired Wilcoxon test showed a significant difference in
the time taken to perform the test for colors ( p ¼ 0.0015) and
colored words (0.0313) but not in the interference score
( p ¼ 0.0625).
In part A of the trail-making test, all control subjects
connected figures 1e25 without error within 60 s, while 70%
of the subjects with MHAþ required more than 60 s. Three
subjects made at least two errors. Results for part B were
similar: the subjects with MHAþ took longer to complete the
test than the control population did. The statistical analysis
found a significant difference in the time needed to complete
both test A ( p ¼ 0.0137) and test B ( p ¼ 0.0078), but not in
the number of combined errors ( p ¼ 0.25).
3.2. Disorders potentially related to executive functions
ADHD was diagnosed retrospectively for 8 subjects with
MHAþ, who had scores greater than 8 on the 11-item Tarter
scale. No control subject was so diagnosed. The Wilcoxon test
of paired series showed a significant difference between the
two groups ( p ¼ 0.002).
All subjects with MHAþ had at least one episode of
intoxication with violence in their history, compared with only
2 in the control population.
Finally, according to the MINI-DSM IV [44], 7 subjects
with MHAþ were at risk of suicide, but only one subject in the
control group.
4. Discussion
Our investigation of executive functions demonstrated that
alcohol-dependent patients with MHAþ (very high probability
of in utero alcohol exposure) performed significantly more
poorly than the alcohol-dependent patients without MHAþ.
Executive functions are cognitive functions used by subjects
faced with non routine actions to adapt their behavior to the
environment. They are therefore involved in executing inten-
tional behavior, in activities requiring the definition of an
objective and strategy, the planning of actions, cognitive
flexibility and the mobilization of sustained and selective
attention [22]. Their dysfunction could therefore have impor-
tant repercussions on the social functioning of those affected,
as seen frequently in alcohol-dependent people. The relation
between executive function disorders and alcohol exposure is
complex [35] but strong.
Executive dysfunctions are known to occur in general
populations of individuals with alcohol-related disorders. They
have been attributed to the neurotoxicity of alcohol exposure,
especially in the frontal regions [21]. Frontal dysfunction may
only in part be ‘‘constitutional’’ since increases in frontal
atrophy with the duration of alcoholism and improvement with
abstinence have been observed [36]. However, young children
from families with high-density alcoholism seem to be bio-
logically vulnerable to alcohol-related disorder when they are
assessed in executive functioning [15]. Thus, in explaining
executive function disorders in alcoholics, it may be difficult
to determine the components attributable to the neurotoxicity
of alcohol on the one hand and to constitutional vulnerability
on the other hand.
As this work shows, additional complexity arises when the
possible existence of PAE is taken into account. Prenatal
exposure may be associated with the development of both
alcohol-related [20] and executive function disorders [30].
Some executive function disorders seen in alcoholics may be
attributable instead to PAE; our results point towards this. We
therefore consider it necessary to document possible prenatal
alcohol exposure when testing executive functions in alcohol-
dependent patients and suggest that caution is required in
interpreting results from general populations of alcohol-
dependent patients.
The disorders potentially related to executive dysfunctions
(that is, ADHD, violent drinking-related behavior, and
attempted suicide) are also very common among the pop-
ulation exposed in utero to alcohol. The Tarter questionnaire
showed ADHD in 8 of 10 study subjects. These results are
consistent with the international literature on the relationship
between alcoholism and ADHD [1e3,13,38]. Nevertheless,
the control population was also alcohol-dependent and ADHD
was not diagnosed for any of them. Of course, ADHD and
attempted suicide have a much more complex affective and
cognitive background, and even ADHD is clearly related to
affective dysfunction. However the relationship between
ADHD and chronic alcoholism is well known [51]. This
disorder is more frequent among children of alcoholic parents
and among those with a history of alcohol dependence. We
would hypothesize that some of the alcohol-dependent patients
in the studies above were also exposed to alcohol in utero. We
note, however, that in our study, the diagnosis of ADHD was
made retrospectively in a population of patients who had been
alcohol-dependent for several years and who inevitably had
memory problems which could bias the results of the studies.
This work shows that all the patients with MHAþ were
sometimes violent when intoxicated, compared with only 2 in
the control population. Similarly, 7 subjects with MHAþ had
a high risk of suicide, versus only 1 in the control population.
The high incidence of ADHD history among the former may
explain this finding. Tarter et al [50,51] compared alcoholics
with ADHD during childhood with those with no such history
and found the former to have higher psychopathic scores,
more relational and emotional difficulties and a greater trend
198 O. Cottencin et al. / European Psychiatry 24 (2009) 195e200

5. to impulsive alcohol consumption and particularly to severe
psychomotor agitation while intoxicated. We have also
reported that a history of ADHD is linked to early-onset
alcoholism associated with pathological intoxication [16].
Then, Coles et al found that PAE children and those with
a diagnosis of ADHD had equivalent intellectual abilities with
both clinical groups performing more poorly than the control
children, but they found clear distinctions on behavioral and
neurocognitive measures between PAE children and ADHD
children suggesting that the alcohol-affected children did not
have the same neurocognitive and behavioral characteristics as
children with a primary diagnosis of ADHD [14].
5. Limitations
Nonetheless, other causes of the disorders presented
(disorders of and related to executive functions) may have
sources that are either genetic or environmental. The herita-
bility of alcohol dependence is a fertile field for exploration
[39] and future work should document the genetic phenotypes
suggestive of prenatal alcohol exposure. In particular, relations
between violent behavior, the impulsivity encountered in our
population and the genes regulating the serotonergic system
must obviously be explored [23].
On the other hand, environmental conditions during devel-
opment may also be linked to some disorders encountered in the
population tested, especially concerning their history of ADHD
[17], parent’s psychopathological history [7] and of suicidal
behavior [9]. Work inspired by psychodynamics and psycho-
education evidently leads us to temper the hypothesis that the
teratogenicity of alcohol alone is the exclusive cause of these
disorders. Indeed, multiple alternative explanations can be
offered to explain the deficient cognitive performance of the
group with MHAþ. It has been demonstrated that mothers with
alcoholism are less responsive to the needs of their children
than those without alcoholism. Deficient responsiveness of
mothers has been shown to adversely affect social and
emotional development in the offspring [18]. The quality of the
home environment is further compromised in situations where
both parents are alcohol-dependent. It would be of interest in
a further study to explore the environment with the home
environment scale and other descriptors of childhood and adult
developmental markers and conditions. The association
between MHA and PAE cannot be made with validity without
taking into account the environmental conditions the subjects
were exposed to during their childhood. The deficits reported
could also be associated with lack of maternal nurturing (even if
the patients and controls were matched on living conditions
during childhood). Another interpretation could be that
observed ADHD symptoms in the MHAþ group are hereditary
and that these symptoms account for performance differences
on neuropsychological tests [25]. Because of the potential
confounding factors in the environment, it would be helpful to
replicate the study with more subjects.
Moreover, it is quite possible and probably desirable to
consider that the disorders presented by our population result
from the combined effects of genetic, teratologic, and
environmental factors in the development of the phenotype of
executive function impairment. We therefore consider that it is
necessary to document prenatal alcohol exposure carefully in
alcohol-dependent subjects to avoid diagnostic errors. Diag-
nostic errors may lead to inappropriate therapeutic strategies if
they do not take into account the patients’ neuropsychological
disorder.
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