El probable TDAH en preescolares se ve asociado a la percepción parental de dificultades en varias dimensiones del desarrollo y el aprendizaje. Es importante realizar una detección precoz del TDAH en la época preescolar para iniciar de forma temprana intervenciones clínicas y educativas efectivas

Background Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a persistent disorder requiring long-term management. Objectives Our objective was to evaluate the 2-year safety and efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with ADHD. Methods Participants (aged 6-17 years) with ADHD received open-label, dose-optimized LDX 30, 50, or 70 mg/day for 104 weeks. Safety monitoring included treatment-emergent adverse events (TEAEs), vital signs, electrocardiography, and growth. The TEAEs decreased appetite, weight decrease, insomnia events (including insomnia, initial insomnia, middle insomnia, and terminal insomnia), headache, and psychiatric TEAEs were pre-defined as being of special interest. Efficacy was assessed as a secondary objective using the ADHD Rating Scale IV (ADHD-RS-IV), the Clinical Global Impressions-Improvement (CGI-I) scale, and the CGI-Severity (CGI-S) scale. Results Of 314 participants enrolled, 191 completed the study. TEAEs were reported in 89.8% of participants, led to discontinuation in 12.4%, and were reported as serious in 8.9%. TEAEs that were reported by >= 5% of participants and considered by investigators as related to LDX were decreased appetite (49.4%), weight decrease (18.2%), insomnia (13.1%), initial insomnia (8.9%), irritability (8.6%), nausea (6.7%), headache (5.7%), and tic (5.1%). The median time to first onset and duration, respectively, of TEAEs of special interest were as follows: decreased appetite, 13.5 and 169.0 days; weight decrease, 29.0 and 225.0 days; insomnia, 17.0 and 42.8 days; and headache, 22.0 and 2.0 days. Reports of decreased appetite, weight decrease, insomnia, and headache were highest in the first 4-12 weeks. Psychiatric TEAEs were infrequent: psychosis and mania (n = 1), suicidal events (suicidal ideation, n = 2; suicide attempt, n = 1), and aggression events (aggression, n = 14; anger, n = 2; hostility, n = 1). At the last on-treatment assessment (LOTA), mean increases from baseline in vital signs were as follows: pulse rate, 7.0 bpm (95% confidence interval [CI] 5.7-8.2); systolic blood pressure (SBP), 3.4 mmHg (95% CI 2.2-4.5); and diastolic blood pressure (DBP), 3.2 mmHg (95% CI 2.2-4.2). Pre-defined thresholds for a potentially clinically important (PCI) high pulse rate were met at one or more visits by 22 participants (7.0%), for PCI high SBP were met by 45 children (22.4%) and 17 adolescents (15.2%), and for PCI high DBP were met by 78 children 38.8%) and 24 adolescents (21.4%). The mean QT interval corrected using Fridericia's formula (QTcF) decreased from baseline to LOTA (-0.6 ms [95% CI -2.3 to 1.2]; range -50 to ? 53). Mean changes in growth from baseline to LOTA were weight, 2.1 kg (95% CI 1.5-2.8); height, 6.1 cm (95% CI 5.6-6.7); and body mass index (BMI), -0.5 kg/m(2) (95% CI -0.7 to -0.3). There was a general shift to lower z score categories for height, weight, and BMI from baseline to LOTA. The mean change in ADHD-RS-IV from baseline to LOTA was -25.8 (95% CI -27.0 to -24.5) for total score, -12.6 (95% CI -13.4 to -11.9) for the hyperactivity/ impulsivity subscale score, and -13.1 (95% CI -13.8 to -12.4) for the inattention subscale score. At LOTA, 77.9% of participants had a CGI-I score of 1 or 2. In addition, 77.3 and 69.2% of participants were classified as treatment responders, based on a CGI-I score of 1 or 2 and a >= 30% or >= 50% reduction from baseline in ADHD-RS-IV total score, respectively. Conclusions The safety profile of LDX in this longer-term study was similar to that reported in previous studies. The efficacy of LDX was maintained throughout the 2-year study period.

Introduction: ADHD symptoms begin to appear at preschool age. ADHD may have a significant negative impact on academic performance. In Spain, there are no standardized toots for detecting ADHD at preschool age, nor is there data about the incidence of this disorder. Objective: To evaluate developmental factors and learning difficulties associated with probable ADHD and to assess the impact of ADHD in school performance. Methods: We conducted a population -based study with a stratified multistage proportional cluster sample design. Results: We found significant differences between probable ADHD and parents' perception of difficulties in expressive language, comprehension, and fine motor skills, as well as in emotions, concentration, behaviour, and relationships. Around 34% of preschool children with probable ADHD showed global learning difficulties, mainly in patients with the inattentive type. According to the multivariate analysis, learning difficulties were significantly associated with both delayed psychomotor development during the first 3 years of life (OR: 5.57) as assessed by parents, and probable ADHD (OR: 2.34) Conclusions: There is a connection between probable ADHD in preschool children and parents' perception of difficulties in several dimensions of development and learning. Early detection of ADHD at preschool ages is necessary to start prompt and effective clinical and educational interventions.

Attention-deficit hyperactivity disorder (ADHD) has been related to increased rates of unintentional injuries. However, the magnitude of the effect and to which extent variables such as sex, age or comorbidity can influence this relationship is unknown. Additionally, and importantly, it is unclear if, and to which degree, ADHD medications can decrease the number of unintentional injuries. Due to the amount of economic and social resources invested in the treatment of injuries, filling these gaps in the literature is highly relevant from a public health standpoint. Here, we present a protocol for a systematic review and meta-analysis to estimate the relationship between ADHD and unintentional injuries and assess the impact of pharmacological treatment for ADHD METHODS AND ANALYSIS: We will combine results from 114 bibliographic databases for studies relating ADHD and risk of injuries. Bibliographic searches and data extraction will be carried out independently by two researchers. The studies' risk of bias will be assessed using the Newcastle-Ottawa Scale. Articles reporting ORs or HRs of suffering an injury in ADHD compared with controls (or enough data to calculate them) will be combined using Robust Variance Estimation, a method that permits to include multiple non-independent outcomes in the analysis. All analyses will be carried out in Stata. Age, sex and comorbid conduct disorders will be considered as potential causes of variance and their effect analysed through meta-re

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<bold>d</bold>). 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.

The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse of ADHD symptoms upon discontinuation of medication treatment in children, adolescents, and adults with ADHD who have responded to medication treatment and to explore differences among different medications in maintaining treatment response. Randomized withdrawal studies of dexmethylphenidate hydrochloride (d-MPH), methylphenidate modified-release (MPH-LA), lisdexamphetamine dimesylate (LDX), guanfacine extended-release (GXR), and atomoxetine (ATX) in both children/adolescents and adults with ADHD were reviewed. The percentage of relapse was significantly higher and the time-to-relapse significantly shorter with placebo compared to active treatment in patients who were previously stable on 5 weeks to 1 year of active treatment, suggesting clinically significant benefit with continued long-term pharmacotherapy. However, percentage of relapse at each time point studied after discontinuing stimulants and GXR appears substantially higher than observed when discontinuing ATX, suggesting longer maintenance of response after discontinuing ATX than after stimulants and GXR. Additionally, slope of relapse percentages over time appears to be more rapid with stimulants or GXR than with ATX. T

Nuestro objetivo es realizar un estudio piloto clínico-epidemiológico de trastorno por déficit de atención e hiperactividad (TDAH) en población preescolar. El método utilizado ha sido un estudio poblacional multicéntrico. Evaluamos 1.171 preescolares, el 4,1% de los cuales correspondían a un posible caso de TDAH. Los posibles factores asociados a una presencia de sospecha de TDAH han sido antecedentes familiares de TDAH, consumo de tabaco en el embarazo y antecedentes de dificultades en el desarrollo psicomotor. Es importante realizar una detección precoz del TDAH en la época preescolar para iniciar de forma temprana intervenciones efectivas

In these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication

This post hoc analysis showed that, at the doses tested, patients treated with lisdexamfetamine showed statistically significantly greater improvement in symptoms of ADHD than those receiving OROS-MPH, as assessed using the ADHD-RS-IV and CGI-I. The safety profiles of lisdexamfetamine and OROS-MPH were consistent with the known effects of stimulant medications.

This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ¿ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital sign

Baseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.

Early-onset schizophrenia patients show more early social impairment than early-onset bipolar patients. Intellectual premorbid abnormalities are less specific and probably more linked to early-onset psychosis.

Abnormalities in the dMPFC DN subsystem in patients with a FEP suggest that FC patterns are altered even in the early stages of psychosis.

Background: Our objective was to determine antioxidant defence activity in healthy controls (HC) and healthy unaffected second-degree relatives of patients with early onset psychosis (HC-FHP), and to assess its relationship with familiar environment measured using the Family Environment Scale (FES). Methods: We included 82 HC and 14 HC-FHP aged between 9 and 17 years. Total antioxidant status, lipid peroxidation, antioxidant enzyme activities and glutathione levels were determined in blood samples. Results: There was a significant decrease in the total antioxidant level in the HC-FHP group compared with the HC group (OR = 2.94; p = 0.009), but no between-group differences in the Global Assessment of Functioning (GAF) scale scores. For the FES, the HC-FHP group had significantly higher scores in the cohesion (p = 0.007) and intellectual-cultural dimensions (p = 0.025). After adjusting for these two FES dimensions, total antioxidant status remained significantly different between groups (OR = 10.86, p = 0.009). Conclusions: Although causal relationships cannot be assumed, we can state that family environment is not playing a role in inducing oxidative stress in these healthy subjects. It could be hypothesized that families with affected relatives protect themselves from psychosis with positive environmental factors such as cohesion and intellectual-cultural activities.

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 (R) 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 (FTGDS) 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 FTGDS 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. (C) 2012 Elsevier B.V. All rights reserved.

Both schizophrenia and bipolar disorder have been associated with progressive changes in grey matter (GM) volume. However, the temporal trajectories of these changes are poorly understood. The aim of this study was to assess longitudinal changes in grey matter volume subsequent to the first episode of schizophrenia and of affective psychoses. Adolescent patients with a first episode psychosis (n=26) were scanned twice using magnetic resonance imaging, at first presentation and after a 3-year follow-up period. An age-matched group of healthy volunteers (n=17) was scanned at the same time points. Within-group and between-group changes in regional grey matter volume were examined using voxel-based morphometry. There were significant group by time interactions (p(FDRcorr)<0.05) in the frontal, temporal, parietal, cerebellar cortex, and in the thalamus, mainly reflecting longitudinal reductions in the controls but not in the patients. Subdivision of the patient group revealed that there were similar longitudinal reductions in patients with affective psychoses as in the controls but no volumetric changes in patients with schizophrenia. Psychosis with onset in adolescence or early adulthood may be associated with a delay or a loss of longitudinal reductions in regional grey matter volume that normally occur at this stage of development. These changes may be specific to schizophrenia.

Volumetric brain abnormalities are evident in young adults presenting with a first episode of both affective psychoses and schizophrenia, but there are also significant differences between these two patient groups. Clinical outcome after the first episode may be related to the severity of volumetric abnormalities at presentation.