Epilepsy & Behavior 24 (2012) 329–331
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Epilepsy & Behavior
journal homepage: www.elsevier.com/locate/yebeh
Validation of the Italian version of the Neurological Disorders Depression Inventory
for Epilepsy (NDDI-E)
M. Mula a,⁎, A. Iudice b, A. La Neve c, M. Mazza d, E. Bartolini b, M.F. De Caro c, S. Mazza e,
A.M. Kanner f, R. Cantello a
a
Division of Neurology, Amedeo Avogadro University, Novara, Italy
Division of Neurology, University of Pisa, Italy
Division of Neurology, University of Bari, Italy
d
Department of Neurosciences, Institute of Psychiatry and Psychology, University Cattolica del Sacro Cuore, Rome, Italy
e
Department of Neurosciences, Clinical Neurophysiology and Epilepsy Center, Università Cattolica del Sacro Cuore, Rome, Italy
f
Department of Neurological Sciences, Rush University Medical Center, Chicago, USA
b
c
a r t i c l e
i n f o
Article history:
Received 10 April 2012
Accepted 21 April 2012
Available online 29 May 2012
Keywords:
Epilepsy
Antiepileptic drugs
Depression
Mood disorders
NDDI‐E
Screening instruments
a b s t r a c t
The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed for the rapid detection of a major depressive episode in people with epilepsy. It has been proven to be a user‐friendly screening
instrument. This study describes the development, validation, and psychometric properties of the Italian version of the NDDI-E. A consecutive sample of 120 outpatients with epilepsy has been assessed using the
M.I.N.I. Plus version 5.0.0 and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Italian version. Cronbach's alpha coefficient was 0.851. Receiver operating characteristic analysis showed an area under the curve of 0.943 (CI95% = 0.902–0.985; SE 0.021; p b 0.001), a cut off
score of 13, a sensitivity of 86.2%, a specificity of 89%, a positive predictive value of 71.4%, and a negative predictive value of 95.3%.
© 2012 Elsevier Inc. All rights reserved.
1. Introduction
Mood disorders represent the most frequent psychiatric comorbidity in patients with epilepsy, and the reasons for this are both
biological and psychosocial [1,2]. Epilepsy is a chronic disorder that
brings about a number of social limitations (e.g., driving license, job
opportunities, etc.) and social discriminations that may lead to demoralization, poor self-esteem, and phobic avoidance. On the other
hand, the neurobiological contribution to this association is given
also by neuroanatomical and neurochemical underpinnings such as
the involvement of the temporal lobes [3] and the psychotropic effects of AEDs [4]. Data from community-based studies report lifetime
prevalence rates for depressive disorders in the order of 22%–24%
[5,6]. In selected populations, such as tertiary referral centers or surgery programs, the prevalence is even higher, ranging between 30%
and 50% [7,8]. Such differences partially reflect the severity of the seizure disorder; in fact, depression seems to occur in only 4% of seizurefree patients [9].
A rapid detection of such comorbidity has relevant implications,
being that mood disorders are an important predictor of poor quality
⁎ Corresponding author at: Division of Neurology, Amedeo Avogadro University, C.so
Mazzini 18, 28100 Novara, Italy. Fax: + 39 03213733298.
E-mail address: marco.mula@med.unipmn.it (M. Mula).
1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2012.04.130
of life in epilepsy [10], high rates of side effects of AEDs [11], drugresistance [12], and poor outcome after epilepsy surgery [13]. Nonetheless, such comorbidity frequently goes unrecognized and untreated, but
the availability of user-friendly screening instruments may overcome
this problem.
Among structured or semi-structured clinical interviews for diagnosis of psychiatric disorders, following DSM criteria, Mintzer and
Lopez [14] proposed the Epilepsy Addendum for Psychiatric Assessment (EAPA) to be used with the Mini International Neuropsychiatric
Interview (MINI); a specific version of the Structured Clinical Interview for Axis I disorders (SCID-I) adapted for patients with epilepsy,
named SCID-E, has been developed [15]. Other clinical instruments
have been developed specifically for patients with epilepsy in order
to identify atypical manifestations of mood disorders that are not usually captured by DSM-based interviews such as the Seizure Questionnaire [16] and the Interictal Dysphoric Disorder Inventory [17]. Among
self-rating screening instruments for depressive symptoms, the wellknown Beck Depression Inventory (BDI) has been validated in patients with epilepsy [18]. A six-item, self-report questionnaire, the
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E),
was developed for the rapid and objective detection of major depressive episodes in patients with epilepsy. It has been found to be a very
practical and user-friendly screening instrument in outpatient epilepsy clinics [19]. This study describes the development, validation, and
330
M. Mula et al. / Epilepsy & Behavior 24 (2012) 329–331
psychometric properties of the Italian version of the NDDI-E. It
has been carried out under the auspices of ILAE Commission on
Neuropsychobiology as part of a large project aimed at validating the
NDDI-E in several languages.
2. Methods
2.1. Study sample
A consecutive sample of adult outpatients with epilepsy was invited to participate in the study in four tertiary referral epilepsy centers
(one in the North of Italy, two in the Center, and one in the South). To
be enrolled, the patients had to fulfill the following criteria: (1) diagnosis of epilepsy according to the ILAE criteria; (2) age more than
18 years; (3) no gross cognitive deficits and a sufficient reading ability to manage the questionnaire defined by a reading level more than
6th grade and/or a MMSE (Mini Mental State Examination Score)
>24; (4) absence of severe medical diseases; and (5) be willing to
provide a written informed consent to undergo the experimental
procedures.
2.2. Instruments
All subjects were assessed using the MINI Plus version 5.0.0 [20]
and the NDDI-E [19].
The M.I.N.I. Plus version 5.0.0 is an efficient diagnostic interview
following DSM criteria. It screens for a number of Axis I diagnoses
with brief suicidality and antisocial personality modules. It has been
validated in the United States and in Europe and is available in several
languages. Both instruments, the MINI and the NDDI-E, were administered in a standardized way and in the same sequence in all patients.
2.3. Experimental procedures and statistical analyses
The original English version of the NDDI-E was translated into Italian
by the first author (MM). The translated version was then back translated into English by an Italian English teacher. Finally, the two versions
were compared by a native English speaker who concluded that they
were identical. The Italian version of the NDDI-E was firstly administered to a small sample of 10 subjects in order to identify problems in
comprehension or cultural specificities. No further adaptations were
required.
The MINI was used as a gold standard for diagnosis of current depression. Cronbach's coefficient was used to test internal consistency.
Receiver operating characteristic analysis was computed to establish
specificity and sensitivity. Frequencies of categorical demographic
and clinical variables were analyzed using the χ2 analysis or Fisher's
exact test. Continuous demographic and clinical variables and NDDI-E
scores were compared using the Mann–Whitney test. Analyses were
carried out using SPSS version 15.0 for Windows.
3. Results
A total of 120 outpatients with epilepsy participated in the study.
Clinical and demographic characteristics are shown in Table 1. There
were no major differences across the four centers regarding clinical
and demographic features of the recruited patients.
According to the MINI, a diagnosis of major depression (current
episode) was established in 29 (24.2%) patients. Depressed subjects
were more likely to have a lower educational level as compared to
non-depressed patients (high school completed 24.1% vs. 49.5%; ChiSquare = 13.493; p = 0.009), had a previous history of a mood disorder
(55.2% vs. 23.1%; Chi-Square = 10.623; p = 0.002), and were more likely to be taking topiramate (20.7% vs. 3.3%; Chi-Square = 9.590; p =
0.006). There was no difference in demographic features (i.e., age and
gender), epilepsy type, seizure pattern, and frequency. As expected,
Table 1
Clinical and demographic features of the study sample.
N = 120 (%)
Age, mean ± SD
Gender
Male
Female
Age at onset epilepsy, mean ± SD
Epilepsy type
Focal
Generalized
Brain MRI normal
Therapy
None
Monotherapy
Dualtherapy
Polytherapy
MINI — depressive episode current
NDDI‐E total score, median [range]
NDDI-E total score in depressed subjects, mean ± SD
44.9 ± 14.4
60 (50)
60 (50)
26.0 ± 18.4
90 (75)
30 (25)
63 (52.5)
6 (5)
71 (59.2)
30 (25)
13(10.8)
29 (24.2)
10.5 [6–22]
16.8 ± 3.1
the depressed patients had higher NDDI-E scores as compared to the
non-depressed patients (16.8 ± 3.1 vs. 9.5 ± 2.9; Z = 7.204; p b 0.001).
All patients had no major difficulties in understanding or answering the questions of the Italian version of the NDDI-E. Cronbach's
alpha coefficient was 0.851, which indicates an excellent internal consistency. Receiver operating characteristic analysis showed an area
under the curve of 0.943 (CI95% = 0.902–0.985; SE 0.021; p b 0.001).
At a cut off score >13, the NDDI-E showed a sensitivity of 86.2%, a
specificity of 89%, a positive predictive value of 71.4%, and a negative
predictive value of 95.3% (Table 2).
4 . Discussion
The Italian version of the NDDI-E showed excellent psychometric
properties with an internal consistency comparable to that reported
by its original authors [19]. The slightly lower specificity of the Italian
version compared to the original study can be due to the small sample
size, but it is important to acknowledge that it is higher than that
reported in other validation studies of translations of this instrument
[21]. Our study further confirms that the NDDI-E represents a useful
screening instrument to detect major depressive episodes in patients
with epilepsy, with good psychometric properties. Well‐known selfrating scales for depressive symptoms, such as the BDI, showed an excellent sensitivity (93%) but a lower specificity (81%) and a poor positive predictive value (47%) for major depressive episodes in epilepsy
[18], as compared to the original version of the NDDI-E and our
results.
The present study identified a slightly different cut off score compared to the original English version, namely 13 instead of 15. This
may be partially explained by minimum cross-cultural differences.
In our study, patients with epilepsy and depression were more
likely to have low educational achievements, to have a previous history of a mood disorder, and to be taking topiramate as compared
to the non-depressed subjects. All these variables have been widely
Table 2
ROC and diagnostic efficiency of the Italian version of the NDDI-E for the diagnosis of
current depression.
Cut off Sensitivity Specificity PPV
score
11
12
13
14
15
89.7
86.2
86.2
79.3
75.9
79.1
86.8
89.0
94.5
95.6
NPV AUC
CI95%
SE
P value
71.4 95.3 0.943 0.902–0.985 0.021 b0.001
PPV = positive predictive value; NPV = negative predictive value; AUC = area under
the curve.
M. Mula et al. / Epilepsy & Behavior 24 (2012) 329–331
reported in the current and past literature, pointing out the relevance
of psychosocial and neurobiological variables in the etiology of mood
disorders in epilepsy [22,23]. However, the phenomenological spectrum of mood symptoms in epilepsy is likely to be large and complex
with a number of variables involved, such as peri-ictal symptoms, the
high comorbidity between mood and anxiety disorders, the underlying neurologic condition, and the psychotropic effect of AEDs. It is,
thus, evident that the NDDI-E cannot replace a complete mental
state examination but can be used as a screening tool to identify subjects that may require a more accurate examination.
In conclusion, the Italian version of the NDDI-E was well received
and understood by all patients and proved to be a reliable and valid
instrument to screen for major depressive episodes in patients with
epilepsy. Access to this version could lead to a better recognition of
depression in the Italian population of patients with epilepsy, with a
number of applications in both clinical and research settings.
Acknowledgments
Authors report no financial interests or potential conflicts of interest with the present paper. The authors thankfully acknowledge
Drs. A.E. Marotta, G. Della Marca, C. Vollono, S. Dittoni, and C. Di
Blasi who took part in the data collection. This report was written
by experts selected by the International League Against Epilepsy
(ILAE). However, opinions expressed by the authors do not necessarily represent official policy or position of the ILAE unless otherwise
stated.
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