Epilepsy & Behavior 24 (2012) 329–331 Contents lists available at SciVerse ScienceDirect 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. References [1] Kanner AM, Balabanov A. Depression and epilepsy: how closely related are they? 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