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Background Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival. Methods In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed. Results In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus. Conclusion From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

To describe the methylphenidate (MPH) effects on weight, height, and body mass index (BMI) in a Spanish sample diagnosed with attention-deficit/hyperactivity disorder (ADHD).Patients (6-18 years) diagnosed with ADHD treated at our Unit with MPH in the last 10 years were included in an observational longitudinal study. Weight, height, and BMI Z scores were measured at baseline and at last follow-up.Three hundred forty-two patients (mean [standard deviation] age: 10.7 [3.8] years, 80% males) were included. Mean dose was 1.25 (0.40) mg/(kg·d). After 27 (14-41) months taking MPH, weight and BMI standard deviation score (SDS) were reduced by treatment (baseline weight-SDS: 0.34 [1.22], follow-up weight-SDS: -0.06 [1.38], t-test p 0.001; baseline BMI-SDS: 0.35 [1.10], and follow-up BMI-SDS [SDS]: -0.23 [1.08], t-test p 0.001). In the whole sample, no differences in height before and after treatment were observed. However, considering only the group of patients who were children 6-12 years (68.6%) when starting treatment, height was slightly affected (baseline height-SDS: 0.04 [1.14], follow-up: -0.10 [1.11], p 0.001). This effect was not observed if treatment was started during adolescence. Linear regression analysis showed that age starting MPH (B = 0.07, p = 0.003), dose (B = -0.50, p = 0.001), and duration of treatment (B = 0.07, p = 0.031) affect follow-up height.MPH slightly decreased weight and BMI in this group of ADHD patients followed naturalistically over 2.2 years, and slightly affected height only if treatment was started before the age of 12. Girls, children who started treatment being younger or children on higher MPH doses, showed greater impact in height.

Resumen: Objetivos: El objetivo de este estudio es validar la versión en castellano del ADHD-RS-IV (ADHD-RS-IV.es) en una muestra española. Métodos: A partir de una muestra total de 652 niños y adolescentes (rango edad: 6-17 años; media [DE] = 11,14 [3,27] años), se incluyó a 518 pacientes con TDAH (criterios DSM-IV-TR) y a 134 controles sanos. Para la evaluación de la estructura factorial, la validez y la fiabilidad de la escala se realizó un análisis factorial confirmatorio (CFA) mediante structural equation modeling en una matriz de correlaciones policóricas, y usando el método de máxima verosimilitud para la estimación. Se calcularon la validez discriminante y su valor predictivo mediante curvas receiver operating characteristics. Resultados: La escala en castellano mostró una consistencia interna elevada, tanto para la escala total como para sus subescalas. El coeficiente alfa de Cronbach era 0,94 para la escala total y ≥ 0,90 para las subescalas. Los valores alfa ordinales eran 0,95 para la escala total y ≥ 0,90 para las subescalas. El análisis CFA mostró un modelo de 2 factores (inatención e hiperactividad/impulsividad) intercorrelacionados. La escala ofrece buen poder discriminante (AUC = 0,97). Conclusiones: La versión española del ADHD-RS-IV (ADHD-RS-IV.es) mostró una estructura bifactorial consistente con los modelos del DSM-IV-TR y DSM-5, y con el modelo propuesto por el autor de la escala original. Además, posee un alto poder discriminante, lo que lo convierte en un instrumento válido y fiable para medir la presencia y severidad de síntomas de TDAH en la población española. Abstract: Objectives: The purpose of this study is to validate a Spanish-language version of the 18-item ADHD Rating Scale-IV (ADHD-RS-IV.es) in a Spanish sample. Methods: From a total sample of 652 children and adolescents aged 6 to 17 years (mean age was 11.14 ± 3.27), we included 518 who met the DSM-IV-TR criteria for ADHD and 134 healthy controls. To evaluate the factorial structure, validity, and reliability of the scale, we performed a confirmatory factor analysis (CFA) using structural equation modelling on a polychoric correlation matrix and maximum likelihood estimation. The scale's discriminant validity and predictive value were estimated using ROC (receiver operating characteristics) curve analysis. Results: Both the full scale and the subscales of the Spanish-language version of the ADHD-RS-IV showed good internal consistency. Cronbach's alpha was 0.94 for the full scale and ≥ 0.90 for the subscales, and ordinal alpha was 0.95 and ≥ 0.90, respectively. CFA showed that a two-factor model (inattention and hyperactivity/impulsivity) provided the best fit for the data. ADHD-RS-IV.es offered good discriminant ability to distinguish between patients with ADHD and controls (AUC = 0.97). Conclusions: The two-factor structure of the Spanish-language version of the ADHD-RS-IV (ADHD-RS-IV.es) is consistent with those of the DSM-IV-TR and DSM-5 as well as with the model proposed by the author of the original scale. Furthermore, it has good discriminant ability. ADHD-RS-IV.es is therefore a valid and reliable tool for determining presence and severity of ADHD symptoms in the Spanish population. Palabras clave: Trastorno por déficit de atención e hiperactividad, Evaluación, Escala Trastorno por déficit de atención e hiperactividad, Attention-Deficit/Hyperactivity Disorder Rating Scale, Keywords: Attention-Deficit/Hyperactivity Disorder, Assessment, Attention-Deficit/Hyperactivity Disorder rating scale, Attention-Deficit/Hyperactivity Disorder Rating Scale

Background:Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD.Objective:To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD.Methods:We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected ADHD-RS-IV.es and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as>30% reduction from baseline of total ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months.Results:We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower ADHD-RS-IV.es scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment.Conclusion:Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical interview.

Timing is an essential function for the survival of many living organisms. Despite its significance, it is relatively under-researched, particularly in schizophrenia. We examined neurophysiological, neuropathological, imaging and genetic studies of both healthy subjects and subjects suffering from schizophrenia in relation to time perception as measured by interval timing. We found that the data from studies in healthy populations indicate that time perception may be inter-linked with numerous other cognitive functions and share common brain networks. The same networks are implicated in the pathophysiology of schizophrenia. There is also evidence that several neurotransmitter systems, particularly the dopaminergic D2 system, are involved in interval timing. Patients with schizophrenia have been shown to suffer from a distorted sense of time, which has an impact on their cognitive function and results in both positive and negative symptoms. Therefore, genes involved in interval timing can be considered candidate genes for distorted cognition in schizophrenia. We discuss the hypothesis that time perception dysfunction is a primary cognitive dysfunction in schizophrenia.

Background As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP. Materials and methods We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used. Results Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p = 0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p > 0.05). Conclusions The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders. Limitations Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.

Introduccion. La prevalencia del trastorno por deficit de atencion/hiperactividad (TDAH) esta en constante estudio, y hay pocas publicaciones sobre la prevalencia en ninos preescolares. Objetivo. Estudiar la prevalencia de sintomas de TDAH en ninos preescolares usando una escala especifica (ADHD Rating Scale-IV, version preescolar, validada para Espana) desarrollada para esta franja de edad. Sujetos y metodos. Se evalua la prevalencia de posible TDAH en una muestra representativa de preescolares en Navarra y La Rioja usando diferentes puntos de corte. Resultados. Se encuentra un rango de prevalencia de sintomas de TDAH del 2,5-4,1% segun el criterio usado (mas o menos estricto). Conclusiones. Existen herramientas especificas que pueden usarse para evaluar el TDAH en preescolares. La prevalencia de posible TDAH en preescolares en Espana es similar a la encontrada en otros paises. La frecuencia de sintomas en esta franja de edad no es mas alta que en otras edades, por lo que no es cierto que los sintomas de TDAH sean muy prevalentes en la poblacion general de ninos preescolares.