Development of a Short Version of the ADHD Rating Scale-IV.es (sADHD-RS-IV.es).

OBJECTIVE: To develop a short version of the Spanish 18-item ADHD-Rating Scale IV.es (sADHD-RS-IV.es) to be used as a potential screening tool in pediatric population. METHODS: We recruited 652 subjects, ages 6 to 18 (mean ± SD = 11.14 ± 3.27): 518 patients with ADHD (per DSM-IV criteria); and 134 healthy controls. We performed a stepwise logistic regression to select the best subset of ADHD-RS-IV.es items to create a short-form. We calculated internal consistency reliability (Cronbach's and ordinal alphas) and diagnostic accuracy using receiver operating characteristic (ROC) curve. RESULTS: Six items were found to enter the stepwise analysis significantly. Internal consistency was high (Cronbach's alpha = 0.86; ordinal alpha = 0.90) and offered a good concordance with clinician diagnosis and a high discriminatory power (AUC = 0.98) with an optimal cut-off at a score of six points. CONCLUSIONS: This shorter questionnaire (six items) was able to discriminate ADHD cases from healthy controls.

The clinical presentation of major depressive disorder in youth with co-occurring obsessive-compulsive disorder.

BACKGROUND: Major depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth. METHODS: A sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis. RESULTS: Youth with MDD and OCD, compared to those with MDD and no OCD, had more severe MDD (Cohen's d = 0.39) and more reported moderate to severe depression (75 % vs 61 %). When accounting for demographic variables and the overall severity of MDD, those with comorbid OCD reported lower levels of anhedonia and more severe difficulties with psychomotor retardation/agitation. No significant differences in the interconnections among symptoms emerged. LIMITATIONS: Data were cross-sectional and self-reported, gold standard diagnostic tools were not used to assess OCD, and the sample size for the group with MDD and OCD was relatively small yielding low statistical power for network analysis. CONCLUSIONS: Youth with MDD and OCD have more severe MDD than those with MDD and no OCD and they experience more psychomotor issues and less anhedonia, which may relate to the behavioral activation characteristic of OCD.

The many faces of microbiota-gut-brain axis in autism spectrum disorder.

The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.

Texas Youth Depression and Suicide Research Network (TX-YDSRN) research registry and learning healthcare network: Rationale, design, and baseline characteristics.

BACKGROUND: American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants. METHODS: TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality symptoms, associated comorbidities, treatment history, services used, and social determinants of health. Subsequent assessments occur every two months for 24 months. RESULTS: Among 1000 participants, 68.7 % were 12-17 years, 24.6 % were ≥ 18 years, and 6.7 % were < 12. Overall, 36.8 % were non-Hispanic Caucasian, 73.4 % were female, and 79.9 % had a primary depressive disorder. Nearly half of the sample reported ≥1 suicide attempt, with rates similar in youth 12-17 years old (49.9 %) and those 18 years and older (45.5 %); 29.9 % of children <12 reported at least one suicide attempt. Depression and anxiety scores were in the moderate-severe range for all age groups (Patient Health Questionnaire for Adolescents [PHQ-A]: 12.9 ± 6.4; Generalized Anxiety Disorder [GAD-7]: 11.3 ± 5.9). LIMITATIONS: The sample includes youth who are receiving depression care at enrollment and may not be representative of non-diagnosed, non-treatment seeking youth. CONCLUSIONS: The TX-YDSRN is one of the largest prospective longitudinal cohort registries designed to develop predictive models for outcome trajectories based on disorder heterogeneity, social determinants of health, and treatment availability.

Factores asociados a la adherencia al tratamiento farmacológico del trastorno por déficit de atención e hiperactividad (TDAH): revisión preliminar / Factors associated with adherence to pharmacological treatment of attention deficit hyperactivity disorder (ADHD): preliminary review

Resumen Introducción: El tratamiento del TDAH es seguro y eficaz, pero con frecuencia existen bajos niveles de adherencia al tratamiento. En este artículo describimos factores asociados a la adherencia des critos en la literatura disponible. Métodos: Realizamos una búsqueda bibliográfica no sistemática sobre artículos recientes sobre la adherencia a la medicación en niños y adolescentes con TDAH. Resultados: Hay factores asociados al propio trastorno, al paciente, al sistema de salud, factores socio-económicos, a la medicación y al entorno que pueden reducir o aumentar la adherencia a la medicación. Algunos factores que mejoran la adhe rencia incluyen: el conocimiento sobre el TDAH, la medicación y sus beneficios y efectos adversos potenciales. Regímenes de medicación sencillos, una vez al día y de liberación prolongada. Edad del paciente menor de 12 años y sexo femenino. Menos barreras de acceso al sistema de salud. Actitud positiva y proactiva de los padres respecto al TDAH y el uso de medicación. Discusión: Se podría optimizar la adherencia y por lo tanto mejorar el pronóstico a largo plazo del TDAH reforzando estos factores que aumentan la adherencia, y reduciendo los sesgos y desconocimiento sobre el TDAH.

Abstract Introduction: ADHD treatment is safe and effective, but often, adherence to t reatment is suboptimal. We studied factors associated to adherence to treatment in ADHD described in the literature. Methods: We conducted a non-systematic bibliographic search on recent articles on medication adherence in children and adolescents with ADHD. Results: There are factors associated with the disorder itself, the patient, the health system, socio-economic factors, the medication and the environment that can reduce/improve medication adherence. Some factors that improve adherence include: knowledge about ADHD, medication and its benefits and potential adverse effects. Simple, once-daily, extended-release medication regimens. Age of the patient less than 12 years and female sex. Fewer barriers to access the health system. Positive and proactive attitude of parents regarding ADHD and the use of medication. Discussion: Adherence could be optimized and therefore the long-term prognosis of ADHD improved by reinforcingfactors that increase adherence, and reducing biases and ignorance about ADHD.

Psychometric properties of Concise Associated Symptom Tracking (CAST) scale in youths and young adults: Findings from the Texas youth depression and suicide research network (TX-YDSRN).

Symptoms of irritability, anxiety, panic, and insomnia are common in patients with depression, and their worsening after antidepressant treatment initiation is associated with poorer long-term outcomes. The Concise Associated Symptom Tracking (CAST) scale was developed to measure these symptoms in adults with major depressive disorder (MDD). Here, we evaluate the psychometric properties of CAST in an ongoing community-based observational study involving children, adolescents, and young adults. Individuals from the ongoing Texas Youth Depression and Suicide Research Network (TX-YDSRN; N = 952) with CAST data available were included. Fit statistics [Goodness of Fit Index (GFI), Comparative Fit Index (CFI), and Root Mean Square Error of Approximation (RMSEA)] from confirmatory factor analyses were used to evaluate the five- and four-domain structure of CAST. Item response theory (IRT) analyses were also used. Individuals were grouped based on age (in years) as youths (8-17) and young adults (18-20). Correlations with other clinical measures were used to inform construct validity. Four-domain (irritability, anxiety, panic, and insomnia) 12-item structure of CAST (CAST-12) was optimal for youths (N = 709, GFI = 0.906, CFI = 0.919, RMSEA = 0.095) and young adults (N = 243, GFI = 0.921, CFI = 0.938, RMSEA = 0.0797) with Cronbach's alpha of 0.87 and 0.88, respectively. Slope of each item exceeded 1.0 on IRT analyses suggesting adequate discrimination for each item. Scores on irritability, anxiety, panic, and insomnia were significantly correlated with similar items on other scales. Together these findings suggest that CAST-12 is a valid self-report measure of irritability, anxiety, insomnia, and panic in youths and young adults.

[Factors associated with adherence to pharmacological treatment of attention deficit hyperactivity disorder (ADHD): preliminary review]. / Factores asociados a la adherencia al tratamiento farmacológico del trastorno por déficit de atención e hiperactividad (TDAH): revisión preliminar.

INTRODUCTION: ADHD treatment is safe and effective, but often, adherence to t reatment is suboptimal. We studied factors associated to adherence to treatment in ADHD described in the literature. METHODS: We conducted a non-systematic bibliographic search on recent articles on medication adherence in children and adolescents with ADHD. RESULTS: There are factors associated with the disorder itself, the patient, the health system, socio-economic factors, the medication and the environment that can reduce/improve medication adherence. Some factors that improve adherence include: knowledge about ADHD, medication and its benefits and potential adverse effects. Simple, once-daily, extended-release medication regimens. Age of the patient less than 12 years and female sex. Fewer barriers to access the health system. Positive and proactive attitude of parents regarding ADHD and the use of medication. DISCUSSION: Adherence could be optimized and therefore the long-term prognosis of ADHD improved by reinforcingfactors that increase adherence, and reducing biases and ignorance about ADHD.

Introducción: El tratamiento del TDAH es seguro y eficaz, pero con frecuencia existen bajos niveles de adherencia al tratamiento. En este artículo describimos factores asociados a la adherencia descritos en la literatura disponible. Métodos: Realizamos una búsqueda bibliográfica no sistemática sobre artículos recientes sobre la adherencia a la medicación en niños y adolescentes con TDAH. Resultados: Hay factores asociados al propio trastorno, al paciente, al sistema de salud, factores socio-económicos, a la medicación y al entorno que pueden reducir o aumentar la adherencia a la medicación. Algunos factores que mejoran la adherencia incluyen: el conocimiento sobre el TDAH, la medicación y sus beneficios y efectos adversos potenciales. Regímenes de medicación sencillos, una vez al día y de liberación prolongada. Edad del paciente menor de 12 años y sexo femenino. Menos barreras de acceso al sistema de salud. Actitud positiva y proactiva de los padres respecto al TDAH y el uso de medicación. Discusión: Se podría optimizar la adherencia y por lo tanto mejorar el pronóstico a largo plazo del TDAH reforzando estos factores que aumentan la adherencia, y reduciendo los sesgos y desconocimiento sobre el TDAH.

Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study.

Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.

Review of barriers and interventions to promote treatment engagement for pediatric attention deficit hyperactivity disorder care.

Attention deficit hyperactivity disorder (ADHD) is a common and impairing behavioral health disorder, impacting over 5% of children worldwide. There are multiple evidence-based pharmacological and psychosocial treatments for ADHD, and greater service utilization is associated with improved acute and long-term outcomes. However, long-term outcomes are suboptimal as multimodal treatments are often not accessed and most care ends prematurely. This narrative review discusses barriers to engagement for children and adolescents with ADHD and their families as well as interventions to overcome these barriers. Families face a variety of structural and attitudinal barriers, ranging from cost and access to stigma and low self-efficacy to successfully implement change. There are multiple interventions that may enhance engagement with ADHD care including psychoeducation, integration of behavioral services in general medical settings, telehealth as well as specific adaptations to existing ADHD treatments, such as the use of motivational interviewing or shared decision making. Integration of behavioral health into general medical settings and telehealth have been found in controlled studies to increase access by reducing both structural and attitudinal barriers. Adding motivational interviewing, shared decision making and other engagement interventions to evidence-based ADHD treatments has been found to reduce attitudinal barriers that translates into improved participation and satisfaction while enhancing outcomes. However, little is known about how to promote extended engagement with ADHD services even though a chronic care model for ADHD is recommended.

Clinical and Neuropsychological Predictors of Methylphenidate Response in Children and Adolescents with ADHD: A Naturalistic Follow-up Study in a Spanish Sample.

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.

Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756.

Weight, Height, and Body Mass Index in Patients with Attention-Deficit/Hyperactivity Disorder Treated with Methylphenidate.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Lisdexamfetamine dimesylate: a new therapeutic option for attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is associated with substantial functional, clinical and economic burdens. It is among the most common psychiatric disorders in children and adolescents, and often persists into adulthood. Both medication and psychosocial interventions are recommended for the treatment of ADHD. However, ADHD treatment practices vary considerably, depending on medication availability, reimbursement and the evolution of clinical practice in each country. In Europe, stimulants and atomoxetine are widely available medications for the treatment of ADHD, whereas in the US approved treatment options also include extended-release formulations of clonidine and guanfacine. Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting, prodrug formulation of dexamfetamine. It is currently licensed in the US, Canada and Brazil, and is undergoing phase III studies in Europe. We performed a PubMed/MEDLINE search looking for recent (2005-2012) scientific papers regarding the pharmacokinetics, pharmacodynamics, efficacy and safety of lisdexamfetamine. The lisdexamfetamine molecule is therapeutically inactive and is enzymatically hydrolysed, primarily in the blood, to the active dexamfetamine. This conversion is unaffected by gastrointestinal pH and variations in normal transit times. Lisdexamfetamine was developed with the goal of providing an extended duration of effect that is consistent throughout the day. Clinical trials have demonstrated robust clinical efficacy of lisdexamfetamine in the treatment of children, adolescents and adults with ADHD with dose-dependent improvements in the core symptoms of ADHD. Studies have further shown that the duration of action of lisdexamfetamine continues for 13 hours post-dosing in children and for 14 hours in adults. The tolerability profile of lisdexamfetamine is consistent with those of other stimulant medications, with decreased appetite, insomnia, abdominal pain and irritability among the more frequent treatment-emergent adverse events, most of which are mild to moderate in intensity and transient in nature. There are currently no parallel-group, head-to-head trial data comparing the efficacy and safety of lisdexamfetamine with other medications for ADHD. However, the available data, including a large effect size and consistent plasma concentrations throughout the day, suggest that lisdexamfetamine is a useful treatment option for patients with ADHD.

Duloxetine in the treatment of adolescents with somatoform disorders: a report of two cases.

BACKGROUND: Our goal was to evaluate the effectiveness, safety and tolerability of duloxetine in the treatment of children and adolescents with somatoform disorder. RESULTS: We describe two cases, those of an 11-year old girl and a 17-year old boy, evaluated in our Department after being studied by a Pediatrician and Neuropediatrician due to complex physical symptoms. The evaluations to rule out medical causes were normal. We diagnosed somatoform disorder. The pharmacological treatments with antidepressants, benzodiazepines, stimulants and mood stabilizers only produced brief and partial improvement. After switching the treatment to duloxetine (30 and 60 mg/day, respectively) both patients experienced a gradual improvement that was maintained at 7 and 14 months. Conclusion. Duloxetine may be effective and well tolerated in the treatment of adolescents with somatoform disorder. Controlled trials are need.

Duloxetina en el tratamiento de adolescentes con trastornos somatomorfos: un informe de dos casos / Duloxetine in the treatment of adolescents with somatoform disorders: a report of two cases

Introducción. Nuestro objetivo fue evaluar la eficacia, seguridad y tolerabilidad de duloxetina en el tratamiento de adolescentes con trastorno somatomorfo. Resultado. Describimos dos casos (chica 11 años y varón 17 años) evaluados en nuestro Departamento después de ser valorados por Pediatra y Neuropediatría por síntomas físicos complejos. Las evaluaciónes para descartar causas médicas fueron normales. Realizamos un diagnóstico de trastorno somatomorfo. El tratamiento farmacológico con antidepresivos, benzodiacepinas, estimulantes y estabilizadores del humor sólo produjouna mejoría breve y parcial. Tras cambiar el tratamiento aduloxetina (30 y 60 mg/día respectivamente) los pacientes experimentaron una mejoría gradual y se mantuvo 7 y 14meses. Conclusión. La duloxetina puede ser eficaz y bien tolerada en adolescentes con trastorno somatomorfo. Son necesarios ensayos controlados (AU)

Background. Our goal was to evaluate the effectiveness, safety and tolerability of duloxetine in the treatment of children and adolescents with somatoform disorder. Results. We describe two cases, those of an 11-year old girl and a 17-year old boy, evaluated in our Department after being studied by a Pediatrician and Neuropediatrician due to complex physical symptoms. The evaluations to rule out medical causes were normal. We diagnosed somatoform disorder. The pharmacological treatments with antidepressants, benzodiazepines, stimulants and mood stabilizers only produced brief and partial improvement. After switching the treatment to duloxetine (30 and 60 mg/day, respectively) both patients experienced a gradual improvement that was maintained at 7 and 14 months. Conclusion. Duloxetine may be effective and well tolerated in the treatment of adolescents with somatoform disorder. Controlled trials are need (AU)

Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit-hyperactivity disorder and bipolar disorder.

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.

Pediatric bipolar disorder in a Spanish sample: results after 2.6years of follow-up.

INTRODUCTION: Bipolar disorder (BD) often starts in childhood or adolescence. There is considerable scepticism outside the United States over the validity, stability and prevalence of BD in children and adolescents. Persistence of course lends support to the validity of a diagnosis. OBJECTIVES: To describe the longitudinal course of pediatric BD in a Spanish sample over a median follow-up period of 2.6years and to examine risk factors associated with outcome. METHODS: We retrospectively reviewed the medical records of all children and adolescents (N=38) with DSM-IV-TR BD-I, II and NOS evaluated in the Child and Adolescent Psychiatry Unit, University of Navarra (Pamplona, Spain) from 1999 to 2005. We used the NIMH Lifetime Mood Chart and the Clinical Global Impression-Severity Scale to assess clinical course. RESULTS: 79% (N=30) were boys and 21% (N=8) were girls; 44.7% (N=17) had BD-I, 5.3% (N=2) BD-II, and 50% (N=19) BD-NOS. Median (inter-quartile range: IQR: Q25; Q75) age at diagnosis was 13.9 (10.64; 15.84). Median follow-up period was 2.6years (0.91; 3.66). Mean percentage of time in an episode was 46.17% (23.36; 75.26), and it was longer in younger children (p<0.05). 2.6% had rapid cycling. At the end of follow-up, only 47% achieved remission or recovery. Younger children showed a worse treatment response (p<0.05). We found higher rates of hospitalization in children with ADHD (21%) (p<0.05). CONCLUSION: Children with BD had a chronic course with little interepisodic recovery. BD can be diagnosed in children using DSM-IV-TR criteria. An early age of onset and ADHD comorbidity are risk factors for worse prognosis.

Is there a cortical blood flow redistribution pattern related with perseverative error in schizophrenia?

BACKGROUND: We studied relative cortical blood flow (relCBF) patterns associated to correct performance (CP) and perseverative error (PE) during Wisconsin Card Sorting Test (WCST) execution, in controls and patients with schizophrenia. SUBJECTS AND METHODS: relCBF (regional cortical blood flow (rCBF) / whole cortex blood flow) of 10 well defined cortical regions was measured in 18 patients with schizophrenia and 13 healthy controls by a Technetium - 99 - HMPAO - SPECT, at rest and while they performed WCST. RESULTS: Patients made significantly more PE than controls during WCST performance. In patients, we found a significant correlation between PE and relCBF in right occipital cortex. In controls, we found a significant correlation between CP and relCBF of several cortical regions during WCST execution: left orbitofrontal cortex and left global frontal cortex positively and parietal bilateral cortex negatively. PE was inversely correlated with relCBF in left temporal cortex. CONCLUSIONS: Successful WCST performance is associated to a high left frontal activity in controls but not in patients. The severity of PE during WCST performance is associated to a low left frontal-temporal activity in controls and to a high right parietal-occipital activity in schizophrenia. This may represent a cortical activity redistribution pattern related to perseveration in schizophrenia.

Pediatric bipolar disorder in a Spanish sample: features before and at the time of diagnosis.

INTRODUCTION: Bipolar disorder (BD) often starts in childhood or adolescence. Diagnostic delay is common and may have a negative impact on treatment response and outcome. OBJECTIVES: To describe the clinical characteristics and symptoms of children with BD prior to their diagnosis and at the time of diagnosis in a sample in Spain. METHODS: We retrospectively reviewed the medical records of all children and adolescents (N=38) with a DSM-IV diagnosis of BD evaluated in the Child & Adolescent Psychiatry Unit, University of Navarra, over a 6-year period. We collected the DSM-IV symptoms of BD prior and at the time of diagnosis using the K-SADS-PL interview template. RESULTS: BD was diagnosed in close to 4% of clinic patients. Thirty (79%) were boys and 8 (21%) were girls; 17 (44.7%) had BD-1, 2 (5.3%) BD-2, and 19 (49.9%) BD-NOS. Median age at diagnosis was 13.9 (10.6;15.9). Delay of diagnosis was 1.5 (0.7;3.4) years. Symptoms of BD were similar to those reported in U.S. samples with high rates of severe irritability (94.6%) and psychiatric comorbidity: 92.1% of the BD children had at least one comorbid disorder and 18.4% had three comorbidities, most frequently ADHD (21%) and substance abuse (18.4%). CONCLUSIONS: Clinical findings in this Spanish sample of children with BD closely resembles those described in U.S. clinics. Diagnostic delay, as in the U.S., and frequent misdiagnosis may explain low prevalence estimates found outside the U.S.

Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach.

OBJECTIVE: The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months. METHODS: Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months. RESULTS: Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate. CONCLUSIONS: Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.