642021

research-article2016
ANP0010.1177/0004867416642021ANZJP ArticleEtain et al.

Research

Australian & New Zealand Journal of Psychiatry

Association between childhood 1­–11

DOI: 10.1177/0004867416642021

dimensions of attention deficit © The Royal Australian and

New Zealand College of Psychiatrists 2016

hyperactivity disorder and adulthood Reprints and permissions:

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clinical severity of bipolar disorders

Bruno Etain1,2,3,4, M Lajnef2, J Loftus4,5, C Henry1,2,3,4, A Raust3,

S Gard4,6, JP Kahn4,7, M Leboyer1,2,3,4, J Scott8 and F Bellivier4,9,10

Abstract
Background: Clinical features of attention deficit hyperactivity disorder can be frequently observed in cases with
bipolar disorders and associated with greater severity of bipolar disorders. Although designed as a screening tool for
attention deficit hyperactivity disorder, the Wender Utah Rating Scale could, given its factorial structure, be useful in
investigating the early history of impulsive, inattentive or mood-related symptoms among patients with bipolar disorders.
Methods: We rated the Wender Utah Rating Scale in 276 adult bipolar disorder cases and 228 healthy controls and
tested its factorial structure and any associations with bipolar disorder phenomenology.
Results: We confirmed a three-factor structure for the Wender Utah Rating Scale (‘impulsivity/temper’, ‘inattentiveness’
and ‘mood/self-esteem’). Cases and controls differed significantly on Wender Utah Rating Scale total score and sub-scale
scores (p-values < 10−5). About 23% of bipolar disorder cases versus 5% of controls were classified as ‘WURS positive’
(odds ratio = 5.21 [2.73–9.95]). In bipolar disorders, higher Wender Utah Rating Scale score was associated with earlier
age at onset, severity of suicidal behaviors and polysubstance misuse; multivariate analyses, controlling for age and gen-
der, confirmed the associations with age at onset (p = 0.001) and alcohol and substance misuse (p = 0.001).
Conclusion: Adults with bipolar disorders who reported higher levels of childhood symptoms on the Wender Utah
Rating Scale presented a more severe expression of bipolar disorders in terms of age at onset and comorbidity. The
Wender Utah Rating Scale could be employed to screen for attention deficit hyperactivity disorder but also for ‘at-risk
behaviors’ in adult bipolar disorder cases and possibly for prodromal signs of early onset in high-risk subjects.

Keywords
Bipolar disorder, attention deficit, hyperactivity, impulsivity, onset, misuse, suicide

1Faculté de Médecine, Université Paris-Est Créteil, Créteil, France

2Inserm U955, Equipe Psychiatrie Translationnelle, Créteil, France
3AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d’Addictologie, Créteil, France
4Fondation Fondamental, Créteil, France
5Centre Expert Trouble Bipolaire, Hospital Princesse Grace, Monaco
6Service de Psychiatrie Adulte, Hôpital Charles Perrens Bordeaux, Bordeaux, France
7CHU de Nancy—Hôpitaux de Brabois, Service de Psychiatrie et Psychologie Clinique, Vandoeuvre Les Nancy, France
8Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
9AP-HP, GH Saint-Louis–Lariboisière–Fernand-Widal, Pôle Neurosciences, Paris, France
10Université Paris Diderot, UMR-S 1144, Paris, France

Corresponding author:
Bruno Etain, Centre Expert Troubles Bipolaires, Pôle de Psychiatrie, Hôpital Albert Chenevier, 40, rue de Mesly, 94000 Créteil Cedex, France.
Email: bruno.etain@inserm.fr

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2 ANZJP Articles
Introduction
Bipolar disorder (BD) is highly heterogeneous in terms of
its clinical expression, course and comorbidities. For most
patients, onset occurs during adolescence or young adult-
hood (Bellivier et al., 2014; Etain et al., 2012), but some
(non-specific) symptoms are likely to occur very early dur-
ing childhood (Duffy, 2010; Duffy and Carlson, 2013; Scott
et al., 2013). Retrospective assessment of childhood symp-
toms and clinical dimensions among adult cases with BD
may shed light on several issues such as (1) understanding
links between adult BD syndromes and various childhood-
onset psychiatric conditions (typically attention deficit
hyperactivity disorder [ADHD]), (2) the identification of
(non-)specific precursors of BD according to staging mod-
els and (3) the investigation of associations between these
dimensions and the severity of clinical trajectories of BD in
adults. The Wender Utah Rating Scale (WURS) has been
developed to retrospectively assess childhood symptoms of
ADHD (Ward et al., 1993). Although typically employed as
a screening tool, the WURS is not specific for ADHD and
its factorial structure captures different childhood dimen-
sions (impulsivity/temper, inattentiveness and mood labil-
ity) that transcend diagnostic categories. It is likely that
trans-nosographic symptoms and dimensions assessed by
self-report questionnaires such as the WURS can help
detect features of a BD prodrome characterized by exter-
nalizing behaviors, inattention or emotion dysregulation.
It is noteworthy that BD and ADHD are frequently iden-
tified as co-occurring and ADHD is the second most com-
mon comorbid condition (after anxiety disorders) observed
in pediatric BD (Frias et al., 2015). Furthermore, a recent
Swedish population-based study with the largest BD cohort
ever reported that ADHD was the most common Diagnostic
and Statistical Manual of Mental Disorders (DSM) axis I
comorbid condition in adults (Song et al., 2015). It is pro-
posed that ADHD can be part of a typical developmental
illness trajectory of BD, although this notion is controver-
sial (Duffy, 2012; Skirrow et al., 2012) and the association
may be an artifact arising from the overlap in clinical symp-
toms across the syndromes (for review, see Youngstrom
et al., 2010). However, it is also possible that a shared
genetic vulnerability could explain overlapping symptoma-
tology and/or the existence of a clinically homogeneous
sub-group of BD with ADHD-like features (Faraone et al.,
2012). The use of the WURS in adult patients with BD can
provide further insights regarding the frequency of such
symptoms during childhood and clarify whether sub-
dimensions are particularly encountered in children who
subsequently develop BD.
Second, staging models of BD (Scott et al., 2013)
describe a continuum from unaffected, but an at-risk state
through to non-mood disorders or sub-threshold presenta-
tions (e.g. anxiety, ADHD symptoms) through to minor
then major mood disturbances, depression and mania
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(Duffy et al., 2010). Longitudinal studies are necessary to
help to identify clinical signs that predict transitions to
nosographic clinical entities. However, such prospective
studies are resource-intensive, often suffer from high drop-
out rates (Leopold et al., 2012) and very large samples of
young people are required in order to capture the minority
who will develop BD. Although methodologically weaker,
retrospective studies in adults with established BD can help
point toward some of the sub-syndromal states or precur-
sors that form part of a neurodevelopmental pathway to
BD. In this context, both prospective and retrospective
studies can foster the identification of risk constellations
prior to the development of BD that include multiple ele-
ments such as genetic risk, substance misuse, ADHD fea-
tures, sub-threshold affective symptoms, changes in sleep
and circadian rhythms and mood swings/affective lability
(Leopold et al., 2012). The use of the WURS-derived
dimensions in adult BD cases may thus help to clarify
whether the inclusion of ADHD features in this pathway of
childhood symptoms is clinically relevant and worth inves-
tigating prospectively.
Third, it has been suggested that a history of ADHD fea-
tures in childhood may be associated with a more severe
clinical trajectory for BD and a worse prognosis. For exam-
ple, the presence of ADHD has been associated with earlier
onset of BD (Masi et al., 2006; Perlis et al., 2004), and a
recent systematic review has suggested that BD type I and
comorbid ADHD were significantly associated with suicide
attempts (SA) in children and adolescents with BD (Hauser
et al., 2013). The latter finding has been reinforced by a
Taiwanese nationwide longitudinal study that reported that
ADHD was an independent risk factor for attempted suicide
later in life among adolescents and young adults with BD
(Lan et al., 2015). Also, compared to patients without a life-
time history of ADHD, BD cases with comorbid ADHD
have higher comorbidity rates for axis I disorders, such as
panic disorder and alcohol abuse/dependence (Perugi et al.,
2013; Tamam et al., 2008; Torres et al., 2015). In a sample
of 90 patients with BD, Karaahmet et al. (2013) demon-
strated that ‘WURS-positive’ cases (defined by a total WURS
score >36, which is the cut-off for the Turkish language
version) had an earlier age at onset and a trend to higher
rates of alcohol dependence (Karaahmet et al., 2013). In a
study of 250 adult patients with mood disorders assessed
with the WURS, Joo et al. (2012) showed that patients with
BD II and recurrent depressive disorders scored higher on
the WURS total score as compared to controls, with BD I
cases displaying intermediate scores (Joo et al., 2012).
However, with the exception of one study (Lan et al., 2015),
these results have been obtained in small-scale studies,
mixed samples of BD and non-BD mood disorders or stud-
ies using different assessments of ADHD (presence/absence
of ADHD, WURS scores, etc.). The available research indi-
cates that the influence of ADHD symptoms or sub-syndro-
mal ADHD presentations on the clinical expression of adult
Etain et al. 3
BD requires further clarification and the use of an estab-
lished tool such as the WURS might enhance our under-
standing and allow greater cross-study comparisons.
The aims of this study are (1) to explore the factorial
structure of the 25-item WURS in an independent sample,
(2) to compare total WURS and WURS sub-scale scores in
BD cases and healthy controls and (3) to investigate any
association between ADHD features and markers of the
clinical severity of BD (e.g. suicidal behavior) and illness
complexity (e.g. substance misuse).
Methods
The research protocol (INSERM C0829) received approval
by the Ethical Committee and institutional review board;
written informed consent was obtained from all study par-
ticipants. The consent process involved a detailed descrip-
tion of the study by a psychiatrist supplemented by written
information summarizing the protocol and project for the
individual.
Sample
Individuals referred to the clinic services at four university-
affiliated psychiatric departments in France (Paris/Créteil,
Bordeaux, Nancy) with a presumed diagnosis of BD were
interviewed using the French version of the Diagnostic
Interview for Genetic Studies (DIGS) (Nurnberger et al.,
1994) to assess lifetime Diagnostic and Statistical Manual
of Mental Disorders, 4th edition (DSM-IV) axis I diagno-
ses (American Psychiatric Association, 1994). The study
sample comprised 276 outpatients who met the following
inclusion criteria: aged ⩾18 years old; met DSM-IV criteria
for BD I, II or NOS (not otherwise specified); currently
euthymic (i.e. scoring ⩽5 on both the Montgomery–Asberg
Depression Rating Scale and the Mania Rating Scale)
(Bech et al., 1978; Montgomery and Asberg, 1979) and
willing and able to give written informed consent.
Healthy controls (N = 228) were recruited from adult
blood donors and the general population. Only those who
were free of any personal history of DSM-IV axis I psychi-
atric disorders, as assessed with the DIGS (Nurnberger
et al., 1994), and had no first-degree relatives with a history
of mood disorders, schizophrenia or SA (as assessed with
the Family Interview for Genetic Studies [FIGS]) were
included in the study.
WURS
The WURS is a 25-item self-administered instrument that
retrospectively measures ADHD symptoms experienced by
individuals before the age of 12 years (Ward et al., 1993).
Each item is rated on a 4-point scale. All participants com-
pleted the French version of the WURS, the psychometric
properties of which have been previously described (Caci
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et al., 2010). A threshold of 46 is indicative of a possible
ADHD in childhood and can be used to classify cases as
‘WURS positive’ (Ward et al., 1993).
Clinical indicators of the course of BD
We selected key clinical variables identified as important
characteristics of BD and indicators of a more severe or
complex course including subtype of BD, mode of onset
(age at onset and polarity at onset), lifetime history of SA,
rapid cycling, substance misuse (alcohol, cannabis and
other drugs misuse) or psychotic features (lifetime presence
during at least one mood episode).
Age at onset has been defined as the age at which the
patient fulfilled for the first time the DSM-IV criteria for a
depressive, (hypo)manic or mixed episode based on the
DIGS.
The DIGS allows the recording of several variables for
suicidal behaviors (lifetime history of and number of SA
and lifetime occurrence of at least one violent SA), so we
used this information to create a composite variable with a
0–3 rating, with higher scores indicative of more of the
construct under study. The rating is the sum of the follow-
ing: lifetime presence of SA (rated 0 if absent or 1 if pre-
sent), lifetime presence of violent SA (rated 0 if absent or 1
if present) and presence of multiple SA (0 if only one SA; 1
if two or more SA). We used the term violent suicidal
attempt for any attempt characterized by attempted hang-
ing, the use of firearms, jumping from heights, severe deep
cuts, car crash, burning, gas poisoning, drowning, electro-
cution and jumping under a train (Asberg et al., 1976).
Drug overdoses were considered to be non-violent SA.
Individuals with no SA received a score of 0, and those with
lifetime presence of multiple SA including at least one vio-
lent SA scored 3.
We created a similar composite score for substance mis-
use, categorizing the patients according to no misuse (rated
0), presence of cannabis misuse (rated 1), presence of alco-
hol misuse (rated 2) and presence of cannabis and alcohol
misuse or other drug (cocaine, opiates, amphetamines) mis-
use (rated 3). We used the term misuse for both abuse and/
or dependence.
Statistical analysis
Data analysis was conducted using R program. To take
multiple testing into account, we used a Bonferroni correc-
tion to determine the threshold for significance, which was
set at p ⩽ 0.003.
Factor analysis. We began by conducting an exploratory
factor analysis using a Principal Component Analysis
(PCA) with promax rotation. To measure the appropriate-
ness of PCA, we used the Kaiser–Meyer–Olkin index
(KMO) and Bartlett’s test of sphericity. To define the
Australian & New Zealand Journal of Psychiatry
4 ANZJP Articles
number of factors to retain, we used Parallel Analysis (PA)
(PA implies a Monte Carlo simulation process since
‘expected’ Eigenvalues are obtained by simulating normal
random samples that parallel the observed data in terms of
sample size and number of variables) combined with Cat-
tell’s Scree Test (which identifies the inflexion point on the
Eigenvalue graph). Factor loadings ⩾0.40 were considered
as significant and thus were retained. As we consider inde-
pendent factors, when an item has a factor loading ⩾0.40
for several factors, it was considered as unclassified. For
analyses that required the inclusion of all WURS items, we
classified items with loadings <0.4 with the factor they
showed the highest loading for.
Case–control comparisons and analysis of WURS in the BD
group.  Between-group comparisons were performed using
chi-squared tests for categorical variables and t-tests or
non-parametric tests for continuous variables as appropri-
ate. Odds ratios (OR) and 95% confidence intervals (95%
CI) are given for selected categorical comparisons.
We used linear regressions to take into account the
effects of age at interview and gender as appropriate, e.g.,
when exploring associations between suicidality ratings
and WURS scores (as this behavior can vary according to
age and gender). BoxCox power transformations were used
for all scores to fulfill the normality assumption required
for parametric procedures. When an association was identi-
fied for the WURS total score, this was further investigated
for each sub-scale (representing the factors derived from
the PCA).
Results
Sample.  The BD group consisted of 276 patients with BD
(62% female) and 228 healthy controls (51% female).
Cases and controls showed significantly different gender
distributions (p = 0.02), but mean age at interview was not
significantly different (44.13  ± 12.2 vs 41.83  ± 12;
p = 0.08). The clinical characteristics of BD cases are shown
in Table 1.
Factor analysis.  We established that PCA was an appropri-
ate procedure (KMO equal to 0.93 and Bartlett’s test
p < 10−6). Using both the PA and Cattell’s Scree Test, three
factors were extracted, accounting for 52% of the variance.
Items and PCA factor loadings in the whole sample are pre-
sented in Table 2.
Factor 1 was labeled ‘impulsivity/temper’ and
explained 37% of the variance. It included 11 items such
as ‘having temper outburst, tantrums’ or ‘being hot tem-
pered, low boiling point’. Factor 2 was labeled ‘inatten-
tiveness’ and explained 8% of the variance. It contained
9 items such as ‘having concentration problems, easily
distracted’ or ‘did not achieve up to potential’. Factor 3
was labeled ‘mood/self-esteem’ and explained about 7%
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of the variance, and the 5 items included ‘feeling sad or
blue, depressed, unhappy’ or ‘having low opinion of
myself’. Four items had loadings <0.40 (items 3, 8, 21,
22) and were allocated as noted in the methods. Item 13
(‘moody, ups and downs’) had equal loadings on two fac-
tors, so it was classified with the ‘impulsivity/temper’
factor as this was where it loaded in a previous study
(Caci et al., 2010).
Case–control comparisons.  As shown in Table 3, cases and
controls were significantly different for all WURS scores.
Furthermore, 22.5% of BD cases versus 5.3% of controls
were classified as WURS positive (OR  = 
5.21; 95%
CI = [2.73, 9.95]; p < 0.0001).
Linear regression showed that the differences between
cases and controls remained significant when controlling
for age and gender (see Table 4).
Associations between WURS scores and clinical characteristics
of BD.  An earlier age at onset of BD was significantly cor-
related with a higher WURS total score (r = −0.23; p < 10−4).
A ‘positive WURS’ was associated with early onset (onset
before 22 years old) (32% vs 15% for later onset, OR = 2.70,
95% CI = [1.49, 4.89], p = 0.001).
A ‘positive WURS’ was also associated with alcohol
misuse (38% vs 20% for no alcohol misuse, OR = 2.46,
95% CI = [1.22, 4.98], p = 0.01) and cannabis misuse (44%
vs 20% for no cannabis misuse, OR = 3.01, 95% CI = [1.29,
7.05], p = 0.01).
An association was found between WURS total
score and the composite scores for increasing severity
of substance use (Figure 1) and for suicidal behaviors
(Figure 2).
No differences for WURS total score were observed for
cases classified according to BD subtype (p = 0.65), polar-
ity at onset (p = 0.46), lifetime history of psychotic symp-
toms during mood episodes (p = 0.77) or rapid cycling
(p = 0.99).
Multivariate analysis
As shown in Table 5, linear regression analysis (controlling
for potential confounders) confirmed significant associa-
tions between WURS total score, earlier age at onset of BD
and higher severity of alcohol and substance misuse, but
did not find a significant association with severity of sui-
cidal behaviors.
Scores for the three factors (derived from the PCA)
identified significant associations between age at onset,
severity of misuse and the Impulsivity/Temper,
Inattentiveness and Mood/Self-esteem sub-scales (all
p-values ⩽ 0.003), but again there was no association
between any of these factors and the composite measure of
suicidal behaviors (data not shown).
Etain et al. 5

Table 1.  Clinical characteristics of cases with bipolar disorder (BD).

Variables N included in analysis Cases with BD

BD I 276 71%

BD II 23.2%

BD NOS 5.8%

Mean age at onset (SD) 265 25.41 (9.6)

Mean duration of the illness in years (SD) 261 18.83 (12.2)

Depressive polarity at onset 260 62%

Mean number of major mood episodes (SD) 224 6.07 (4.4)

⩾1 psychotic mood episode 263 56%

Rapid cycling 243 23%

⩾1 mixed episode 234 24%

⩾1 suicide attempt 262 42%

Mean number of suicide attempts (SD) 110 2.35 (2.0)

Mean age at first suicide attempt (SD) 108 30.04 (11.7)

⩾1 violent suicide attempt 110 26%

Tobacco smoking status 263  

 Never-smoker 37%
  Former smoker 22%
  Current smoker 41%

Alcohol misuse 262 16%

Cannabis misuse 262 10%

Other substances misuse 260 4%

NOS: not otherwise specified; SD: standard deviation.

Percentages are reported as the nearest whole number.

Discussion it is worthwhile highlighting some of the issues that com-

We confirmed the factorial structure of the French version
of the 25-item WURS in a sample of euthymic BD cases
and healthy controls. The three factors identified
(Impulsivity/Temper, Inattentiveness and Mood/Self-
esteem) replicated the structure previously described in a
French validation study (Caci et al., 2010) and that reported
in studies of patients with other mood disorders (Greenwood
et al., 2013; Joo et al., 2012). Adult BD cases differed sig-
nificantly from healthy controls for the WURS total score
and the three factor scores. A greater magnitude of child-
hood ADHD features was associated with more evidence of
clinical severity and complexity of BD including an earlier
age at onset and comorbid alcohol and substance misuse
(mainly cannabis), but only a trend for a greater array of
suicidal behaviors. In addition to discussing these findings,
plicate the measurement of ADHD symptoms in BD (and
vice versa).
First, it is notable that the design of our study does not
allow us to determine the sensitivity or specificity of the
WURS as a tool to detect ADHD caseness in our BD sam-
ple or the healthy controls. We did not include a structured
interview to ascertain a formal diagnosis of ADHD. This
limitation arose mainly because the version of the DIGS
that is validated for use in French does not include a section
of the diagnosis of ADHD (unlike later versions of the
DIGS). We note that about 20% of WURS scores exceeded
the arbitrary cut-off score (total >46) used to identify prob-
able caseness, so some or all of these individuals may have
true ADHD comorbidity. Having said that, screening tools
such as the WURS can generate a substantial rate of false
positives in clinical samples (as high as

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Table 2.  Principal Component Analysis in the sample of cases and controls.

Item number Factor 1 Factor 2 Factor 3

WURS 61 WURS 25 Impulsivity/temper Inattentiveness Mood/self-esteem
3 1 0.62  
4 2 −0.66
5 3 0.36 0.37  
6 4 0.49  
7 5 0.82  
9 6 0.88  
10 7 0.48  
11 8 0.39  
12 9 −0.79
15 10 0.52  
16 11 −0.73
17 12 0.71  
20 13 0.41 −0.41
21 14 0.84  
24 15 0.43  
25 16 0.49  
26 17 −0.63
27 18 0.44  
28 19 0.46  
29 20 −0.41
40 21 0.23 0.28  
41 22 0.34 0.29  
51 23 0.47  
56 24 0.41  
59 25 0.54  

WURS: Wender Utah Rating Scale.

Darker shades of gray indicate loadings >0.40.
Slighter shades of gray indicate loadings <0.40.
Items in italic are those with no clear factor loading.

Table 3. WURS scores in cases with bipolar disorder (BD) and healthy controls.

WURS scores BD cases (N = 276) Healthy controls (N = 228) p-value

Total score 31.32 (19.0) 16.12 (14.2) <10−6

Impulsivity/temper 12.64 (10.1)   6.22 (6.8) <10−6

Inattentiveness 11.31 (7.3)   7.01 (6.5) <10−6

Mood/self-esteem   7.37 (5.3)   2.89 (3.4) <10−6

WURS: Wender Utah Rating Scale.

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Table 4. WURS scores in cases with bipolar disorder (BD) and healthy controls adjusted for gender and age at interview.

WURS scores Disease status (case vs control) Gender (female vs male) Age at interview

  Beta (SD) p-value Beta (SD) p-value Beta (SD) p-value

Total score 2.36 (0.3) <10−5 −0.34 (0.27) 0.21 −0.01 (0.01) 0.21

Impulsivity/temper 1.47 (0.23) <10−5 −0.32 (0.23) 0.16 −0.02 (0.01) 0.07

Inattentiveness 1.91 (0.22) <10−5 0.17 (0.21) 0.42 −0.01 (0.01) 0.19

Mood/self-esteem 1.84 (0.22) <10−5 0.19 (0.12) 0.38 −0.01 (0.01) 0.24

WURS: Wender Utah Rating Scale; SD: standard deviation.

Positive values of beta indicated association between the scores and BD. p- values in bold remained significant after correction for multiple testing.

Figure 1. WURS total score as a function of substance misuses.

WURS: Wender Utah Rating Scale.

p(Kruskall Wallis test) = 0.005.
After multiple corrections test, no misuse versus cannabis, alcohol and others remained significant (p = 0.0003).

75% in some studies) (Suhr et al., 2009), and the positive
predictive values of the WURS are only around 45% among
alcohol dependent patients (Daigre et al., 2015), around
35% in individuals seeking treatment for substance use dis-
orders (Dakwar et al., 2012) and about the same in patients
with BD (Oncu et al., 2005). Screening for adult ADHD in
BD samples gives rise to similar issues, and about 40% of
the individuals who score positively on the adult self-rating
scale (ASRS-v1.1) do not meet ADHD caseness criteria
(Edebol et al., 2012; McCann and Roy-Byrne, 2004;
Perroud et al., 2014; Torres et al., 2015). However, we were
primarily interested in considering dimensions of ADHD
and potential symptom clusters, not simply studying pres-
entations that exceeded diagnostic thresholds. To this end,
several authors have thus proposed that the WURS rather is
actually measuring clinical manifestations of externalizing
behaviors or other symptoms that are far from specific to
ADHD (Suhr et al., 2009).
An alternative view of our approach is that we have used
the WURS as a multi-dimensional measure to capture
aspects of the complex clinical phenomenology and over-
lapping features of BD and ADHD. This overlap typically
includes impulsivity and inattention and also emotional
lability, and all these dimensions are represented in the fac-
torial structure of the WURS scale. It has been highlighted
that ADHD manifestations in childhood also include an
emotional component (mood swings and emotional labil-
ity), and Shaw et al. (2014) report that emotion dysregula-
tion is found in up to 50% of children with ADHD. The
clinical overlap between ADHD and bipolar mania includes

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Figure 2. WURS total score as a function of severity of suicidal behaviors.

WURS: Wender Utah Rating Scale.

p(Kruskall Wallis test) = 0.02.
After correction for multiple test, 1 versus 2 remained significant (p = 0.0003).

Table 5.  Multivariate analysis using WURS total score as the irritable mood, poor concentration, increased motor activ-
dependent variables and age at onset, severity of misuse and of ity and features that can also be observed in certain sub-
suicide behavior as independent variables. types of bipolar depression. Indeed, the clinical
manifestations assessed in the WURS belong to different
Variables Beta (SD) p-value
psychological domains such as impulsivity, temper, inat-
Intercept 11.3 (0.8) 0.001 tention, unstable mood, low self-esteem and anxiety. As
such, the conclusion in favor of any one position over
Severity Misuse 1a 0.61 (1.33) 0.65
another (i.e. the WURS demonstrates the co-occurrence of
Severity Misuse 2a 1.63 (0.83) 0.06 BD and ADHD phenomena and represents true comorbid-
ity or it highlights early manifestations of BD or indicates
Severity Misuse 3a 3.93 (1.09) 0.001
non-specific psychopathological manifestations of several
Severity Suicide 1b −0.53 (0.63) 0.41 putative disease trajectories) is far from easy. Our own
review of the literature indicated that more than half of
Severity Suicide 2b 1.03 (0.73) 0.16
individuals who developed BD presented a putative pro-
Severity Suicide 3b 1.37 (1.13) 0.23 drome prior to 14 years of age and that this frequently
included a mixture of precursors such as mood lability,
Age At Onset (AAO) −0.09 (0.03) 0.001 depressive episodes, anxiety, sleep disorders, conduct prob-
WURS: Wender Utah Rating Scale; SD: standard deviation. lems, attention and concentration impairments, altered
Severity Suicide 0: no suicide attempt; Severity Suicide 1: unique non- energy patterns and/or a family history of mania or depres-
violent suicide attempt; Severity Suicide 2: multiple or violent suicide sion (Geoffroy et al., 2015; Leopold et al., 2012).
attempts; Severity Suicide 3: multiple suicide and violent attempts, The validation study of the WURS (Ward et al., 1993)
– Severity Misuse 0: no lifetime substance misuse (excluding tobacco);
Severity Misuse 1: alcohol misuse alone; Severity Misuse 2: cannabis mis-
selected the 25 items that showed the greatest mean differ-
use alone; Severity Misuse 3: alcohol and cannabis misuse or any other ence between subjects with ADHD and healthy controls.
substances misuse (cocaine, opiates, amphetamines). However, in addition to externalizing behaviors, the items
aScore for the construct compared to the reference level (absence of
included (anxiety, worry, inattention, daydreaming, sleep
lifetime misuse).
bScore for the construct compared to the reference level (absence of
problems, stubborn behavior, poor concentration) bear a
suicidal behavior). striking resemblance to the prodromal signs identified in
longitudinal studies of high-risk offspring of BD parents

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Etain et al. 9
(Duffy, 2010; Duffy et al., 2010; Egeland et al., 2012) and
other risk syndromes (Scott et al., 2013). A review of pro-
spective studies exploring clinical risk factors for BD found
evidence for at least two heterotypic trajectories, one char-
acterized by prodromal anxiety symptoms and the other by
high impulsivity, aggression, externalizing behaviors and
mixed dysphoric features (Faedda et al., 2014). As such,
high WURS scores may simply reflect heterotypia in the
developmental trajectory of BD and such findings should
encourage clinicians to explore not only problems related
to ‘early mood deregulation’ but also a larger range of
(non-)specific precursors that may be markers of future
morbidity independent of the specific late-stage syndrome
(Hickie et al., 2013).
The utility of the research assessment we have under-
taken is that it demonstrates an association between high
scores on the WURS and specific aspects of a more severe,
complex, BD phenotype characterized by an earlier age at
onset and an increased lifetime severity of suicidal attempts
and substance misuse. The association between higher
WURS and earlier onset of BD could represent higher levels
of true ADHD comorbidity in the early-onset BD sub-group
(since 32% of those with early onset vs 15% of those with
later onset have a positive WURS), and there is corroborat-
ing evidence for such a finding in the literature. For exam-
ple, Greenwood et al. (2013) reported a negative correlation
between age of onset and all WURS scores except for inat-
tention. The bidirectional and robust comorbidity between
pediatric BD type I and ADHD has been well documented
in pediatric and adult studies in both clinical and epidemio-
logical samples (Biederman et al., 2013). In the Systematic
Treatment Enhancement Program for Bipolar Disorder
(STEP-BD) cohort of adults, the overall lifetime prevalence
of ADHD was about 10% and patients with BD and comor-
bid ADHD reported the onset of their mood disorder about
5 years earlier than other cases (Nierenberg et al., 2005).
Also, the bidirectional association between pediatric BD
and ADHD has been documented in clinical and epidemio-
logical samples (Biederman et al., 2013) and ADHD is
reported to be a significant risk factor for switching from
unipolar to BD in youth (Biederman et al., 2009; Chen et al.,
2015). However, the evidence does not suggest the associa-
tion between the WURS ratings, and an earlier age is due to
misdiagnosis of ADHD and juvenile mania in our sample. It
is notable that the earliest age at onset in our sample is
14 years old, corresponding to the often-noted lack of pre-
pubertal mania in European clinical populations (Douglas
and Scott, 2014; James et al., 2014). Furthermore, it is
unlikely that mood swings or emotion lability dramatically
accounts for the differences observed between groups in our
study (as this factor accounts for only 7% variance in the
WURS total score). The largest proportion of the variance
was explained by the impulsivity/temper factor.
We have previously reported evidence linking impulsiv-
ity to alcohol and substance misuse in BD (Etain et al.,
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2013) and to dimensions of hostility/impulsivity to suicidal
behaviors (Parmentier et al., 2012). Two meta-analyses have
demonstrated that children with ADHD were more likely to
develop disorders of abuse/dependence for nicotine, alco-
hol, marijuana, cocaine and other substances (Charach et al.,
2011; Lee et al., 2011). The use of the WURS might shed
light on how trans-diagnostic symptoms may accelerate or
exaggerate disorder-related phenomena such as age at onset
or patterns of risky or self-harming behaviors. The clinical
implication is to systematically screen patients with BD for
this early component to identify those who might be at risk
for such high-risk behaviors.
This study has several methodological limitations. As
noted, using the WURS to retrospectively measure child-
hood ADHD features is the main weakness, and recall biases
and cognitive deficits may further confound the assessment.
Responses could also be biased by residual mood symptoms
although our sample has been assessed during a period of
euthymia. We used no external validation of the self-assess-
ment made by individuals. We used the WURS as an indica-
tor of ADHD during childhood but provided no formal
diagnosis for childhood or adulthood persistent ADHD.
Therefore, our study was not an attempt to assess a retro-
spective diagnosis of ADHD. Finally, the cut-off of 46 that
we used to define WURS-positive cases is not universally
accepted as the optimal cut-off score (Suhr et al., 2009). We
also did not provide any adult ADHD assessment to study
the continuity between ADHD symptoms from childhood to
adulthood. Although this is one of the larger studies on this
topic, false negative findings could have emerged such as
the reduced magnitude in association with suicidal behav-
iors (after controlling for other variables).
Conclusion
We found that ADHD features were common in adults with
BD, with 22% of cases versus 5% of controls having a posi-
tive WURS score. The presence of ADHD features in child-
hood was associated with early onset, suicidal behavior and
substance misuse. Both the total WURS score and scores
on the three factor sub-scales (Impulsivity/Temper,
Inattentiveness and Mood/Self-esteem) were linked with
early onset and substance misuse. Further clinical studies
of BD cases and individuals at high risk of developing BD
will enable better understanding of how ADHD features fit
into a neurodevelopmental model of BD and whether the
features predict a specific illness trajectory or represent an
epiphenomena (such as overlapping clinical features).
Additional research would also be useful to delineate how
the WURS can be integrated into assessment packages of
‘risk constellations’ for adults with complex BD presenta-
tions (Leopold et al., 2012). The systematic investigation of
ADHD features (and a possible diagnosis of childhood
ADHD) especially in those with an early-onset BD and evi-
dence of substance misuse or suicidal behaviors could help
Australian & New Zealand Journal of Psychiatry
10 ANZJP Articles
treatment planning and modify outcomes. Indeed, some
recommendations have been proposed for the management
of patients with mood disorders and comorbid ADHD in
national clinical guidelines (Bond et al., 2012).
Acknowledgements
We thank the patients and controls for participating in this study.
We thank E Abadie, and JR Richard for their assistance.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
work was supported by Institut National de la Santé et de la
Recherche Médicale (INSERM), Assistance Publique des
Hôpitaux de Paris and Fondation FondaMental.
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