Monitoring of metabolic adverse events of second-generation antipsychotics in a naive paediatric population followed in mental health outpatient and inpatient clinical settings: MEMAS prospective study protocol.

INTRODUCTION: Second-generation antipsychotics (SGAs) are widely used in the paediatric population. It is currently established that SGAs may induce metabolic adverse events (AEs) such as weight gain, perturbation of blood lipids or glucose with risk of potential cardiovascular morbidity and mortality. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in children (CAMESA) has published recommendations for monitoring the metabolic AEs of SGAs. Factors that may be associated with the onset of SGA's metabolic AEs and long-term consequences are less studied in the literature. The objectives of our research are to evaluate some factors that can influence the development of the SGA's metabolic AEs and to study clinical adherence to CAMESA guidelines. METHODS AND ANALYSIS: The Monitoring des Effets Métaboliques des Antipsychotiques de Seconde Génération study is a multicenter, prospective, longitudinal observational study with repeated measures of metabolic monitoring over 24 months. Two recruiting centres have been selected for patients under 18 years of age, previously naive of antipsychotics, starting an SGA or who have started an SGA for less than 4 weeks regardless of the diagnosis that motivated the prescription. Assessments are performed for anthropometric measures, blood pressure, blood tests at baseline and 1, 2, 3, 6, 9, 12 and 24 months of follow-up. ETHICS AND DISSEMINATION: The study protocol was approved by the CHU Sainte-Justine's Research Ethics Board (MP-21-2016-1201) in 2016 and obtained institutional suitability for the 'Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal' Research Center in May 2018. For all participants, written consent will be obtained from parents/caregivers as well as the participant's assent in order to enable their participation in this research project. The results of this research will be published. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (number NCT04395326).

Long-Term Metabolic Monitoring of Youths Treated with Second-Generation Antipsychotics 5 Years after Publication of the CAMESA Guidelines Are We Making Progress? Surveillance Métabolique à Long Terme des Jeunes Traités par Antipsychotiques de Deuxième Génération, Cinq ans Après la publication des Lignes Directrices Camesa: Faisons-Nous des Progrès?

OBJECTIVE: The potential metabolic adverse effects of second-generation antipsychotics (SGA) need to be monitored. The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics (CAMESA) offers guidelines for this purpose. We aimed to evaluate the long-term rates of youths receiving monitoring in mental health clinics and document the factors that may influence them. METHOD: The charts of 180 patients (13.3 ± 3.1 years, 54.4% males) receiving SGA treatment for the first time between January 2016 and June 2018 were reviewed. Monitoring was divided into baseline and 1- to 6-month and 9- to 24-month periods. Population under study was stratified into children (4 to 12 years) and adolescents (13 to 18 years). Sociodemographic characteristics, psychiatric diagnosis and comorbidities, prescribed SGAs and comedications, anthropometric measures (AM), blood pressure (BP), blood tests (BT), electrocardiogram, and the psychiatrist's years of practice were collected. Cross tables were used to present the monitoring rates. Categories were compared by covariate analysis. Rates of patients monitored across categories were compared using Fisher exact test. RESULTS: Monitoring rates for AM, BT, and BP were 55%, 47.8%, and 46.7% at baseline; 50%, 41.7%, and 45.2% at 1 to 6 months; and 47.2%, 41.5%, and 40.6% at 9 to 24 months, respectively. Higher monitoring rates were significantly associated with adolescent status (baseline, 1 to 6 months), a diagnosis of psychotic and/or affective disorder (baseline, 1 to 6 months, 9 to 24 months), having ≤1 psychiatric comorbidities (1 to 6 months), high SGA dose (baseline, 1 to 6 months), and clinician's experience (baseline, 9 to 24 months). Significantly lower monitoring rates were associated with the psychostimulant/atomoxetine comedication (baseline, 1 to 6 months, 9 to 24 months). CONCLUSION: Five years after publication of the CAMESA guidelines, metabolic monitoring is conducted for less than half of patients. In our sample, age, diagnostic category, psychiatric comorbidities, SGA dose, clinician's experience, and comedications influenced the monitoring rates. Major progress still needs to be made before reaching a satisfactory level of monitoring.

New p-type Al-substituted SrSnO3 perovskites for TCO applications?

Novel p-type SrSn1-xAlxO3 (x = 0, 0.2, 0.5) perovskites are presented as potential candidates for electro-optical applications. A combined experimental and theoretical study reveals that chemical substitutions can be used as a lever to stabilize oxygen holes in the valence band.

Treatment Patterns, Health Care Resource Utilization, and Health Care Cost Associated with Atypical Antipsychotics or Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in Quebec, Canada.

Objective: To assess treatment patterns, health care resource utilization, and health care costs associated with use of atypical antipsychotics (AAPs) or the nonstimulant guanfacine extended release (GXR) after stimulant therapy for attention-deficit/hyperactivity disorder (ADHD). In Canada, GXR is approved as a monotherapy for children and adolescents with ADHD or as an adjunct to stimulants, and AAPs are commonly used off-label as an adjunct to stimulants. Methods: Health care claims data (January 1, 2007 to March 31, 2016) from Quebec's provincial health plan were assessed for individuals with ADHD, 6-17 years of age, who received ≥1 stimulant followed by a first AAP or GXR prescription (index medication), without a diagnosis for which AAPs are indicated. Results: Overall, 1327 individuals were included (AAPs, 1098; GXR, 229). Rates of discontinuation, augmentation, or switching of the index medication did not differ between AAPs and GXR during the first follow-up year. Discontinuation rates were significantly lower with GXR than with AAPs during the second year (22.0% vs. 35.9%; p = 0.03). GXR and AAPs resulted in similar increases in total health care cost. In GXR users, the increase in prescription drug cost after 6 months was higher than in AAP users, whereas the increase in overall medical cost was higher with AAPs than GXR, owing to more psychiatric department visits. Conclusions: In children and adolescents with ADHD who used AAPs or GXR after stimulants, secondary treatment changes were similar with both treatments after 1 year, but discontinuation rates were significantly lower with GXR than with AAPs in the second year. The greater increase in prescription cost with GXR was balanced by a greater increase in overall medical costs with AAPs, resulting in no overall difference in total health care cost between the two treatments.

Impact of Psychoactive Drug Use on Developing Obesity among Children and Adolescents with Autism Spectrum Diagnosis: A Nested Case-Control Study.

BACKGROUND: Obesity in children on the autism spectrum (AS) is becoming a significant health concern. The purpose of this study was to identify the predictors of obesity in a cohort of AS youth and to assess the impact of psychoactive medication use while exploring the second-generation antipsychotics (SGAs) dose-response curve. STUDY DESIGN: A nested case-control study was conducted using Quebec public administrative databases. Subjects with AS <18 years [≥2 diagnoses International Classification of Diseases: 9th revision (ICD-9): 299.X] were identified (January 1993 to May 2011). Cases were defined as subjects with an obesity diagnosis (ICD-9: 278.X) during the coverage period and matched to 10 controls for age, gender, and follow-up duration. Potential risk factors for obesity (sociodemographic characteristics, other neuropsychiatric conditions, and psychoactive drug use) were evaluated and analyzed using conditional logistic regression. RESULTS: From a cohort of 5369 AS subjects, we identified 135 obesity cases. Among the different risk factors, only SGAs [rate ratio (RR): 1.04, 95% confidence interval (CI): 1.01-1.07] increased the probability of obesity in multivariate analysis. Exposure for ≥12 months increased significantly the likelihood of obesity (RR: 2.01, 95% CI: 1.18-3.42). Higher risk was observed with chlorpromazine-equivalent daily doses ≥100 mg (RR: 2.20, 95% CI: 1.00-4.84). Among SGA users, concomitant antidepressants (per 30-day exposure) slightly increased the probability (RR: 1.08, 95% CI: 1.01-1.15). CONCLUSIONS: Longer and higher SGA exposure increased the risk of obesity, which has to be considered in relation to the paucity of evidence supporting long-term psychoactive medication use in AS children. Results highlight the need to promote optimal use and interventions to mitigate metabolic side effects of SGAs in this population.

A Mindfulness-Based Intervention Pilot Feasibility Study for Elementary School Students With Severe Learning Difficulties: Effects on Internalized and Externalized Symptoms From an Emotional Regulation Perspective.

OBJECTIVE: Students with severe learning disabilities often show signs of anxiety, depression, and problem behaviors such as inattention and conduct problems. Mindfulness-based interventions (MBIs) in school settings constitute a promising option to alleviate these co-occurring symptoms. This pilot study aimed to evaluate the impact of an MBI on symptoms and behaviors of elementary school students with severe learning disabilities. METHOD: A one-group pretest-posttest design was used. The sample comprised 14 students aged 9 to 12 years with special education needs. Both student-report and teacher-report of the Behavior Assessment System for Children, Second Edition were used. RESULTS: Repeated-measures analyses of variance revealed a significant impact of the MBI on symptoms and behaviors such as anxiety, depression, inattention, aggression, and conduct problems. Effect sizes for all variables were considered large (partial η2 = .31-.61). CONCLUSION: These preliminary results indicate that MBIs can reduce the frequency of symptoms and problem behaviors often found in children with learning disabilities in elementary schools. Further multiple baseline experimental trials with a long-term follow-up are warranted to establish more robustly the effect of MBIs for children with learning disabilities.

Combination and switching of stimulants in children and adolescents with attention deficit/hyperactivity disorder in quebec.

OBJECTIVE: To assess the one-year period prevalence of stimulant combination therapy and switching in children/ adolescents with attention deficit/hyperactivity disorder (ADHD) in Quebec, Canada. METHOD: Patients aged 6-17 years, with at least two ADHD diagnosis codes documented in different visits and at least 30 days' supply of a stimulant during their most recent one-year observation period were selected from the Regie de l'assurance maladie du Quebec database (03/2007-02/2012). Combination therapy was defined as at least 30 consecutive days of concomitant use of multiple stimulants with different active moieties, or use of a stimulant and another psychotropic medication. Therapy switching was defined as a prescription claim for a new psychotropic medication less than 30 days before or after the end of supply of a stimulant. The one-year period prevalence of therapy combination and switching was calculated. RESULTS: The one-year period prevalence of combination therapy and switching among 9,431 children and adolescents with ADHD treated with stimulants was 19.8% and 18.7%, respectively. The most frequent combination categories were atypical antipsychotics (AAP: 10.8%), atomoxetine (ATX: 5.5%) and clonidine (5.3%). The most frequent switched-to categories were other stimulants (7.9%), AAP (5.5%) and ATX (4.7%). CONCLUSIONS: Approximately one in five children/adolescents with ADHD on a stimulant experienced combination therapy or therapy switching; however, the majority of the medications used in combination or switching were not label-indicated for the treatment of ADHD in Canada. These results highlight the need for further research to evaluate the risk-benefit of stimulant combination and switching in children and adolescents with ADHD.

OBJECTIF: Évaluer la prévalence sur une période d'un an de la traitement par combinaison et par changement de stimulants chez les enfants et les adolescents souffrant du trouble de déficit de l'attention avec hyperactivité (TDAH) au Québec, Canada. MÉTHODE: Des patients de 6 à 17 ans, ayant au moins deux codes diagnostiques de TDAH documentés à différentes visites et une provision d'au moins 30 jours d'un stimulant durant leur plus récente période d'observation d'un an, ont été choisis dans la base de données de la Régie de l'assurance maladie du Québec (03/2007­02/2012). La traitement par combinaison a été définie comme étant au moins 30 jours consécutifs d'utilisation concomitante de multiples stimulants ayant différentes parties actives, ou d'utilisation d'un stimulant et d'un autre médicament psychotrope. La traitement par changement a été définie comme étant une demande de prescription d'un nouveau médicament psychotrope moins de 30 jours avant ou après la fin d'une provision d'un stimulant. La prévalence sur une période d'un an de la traitement par combinaison et par changement a été calculée. RÉSULTATS: La prévalence sur une période d'un an de la traitement par combinaison et par changement chez 9 431 enfants et adolescents souffrant de TDAH traités par stimulants était de 19,8% et 18,7%, respectivement. Les catégories de combinaison les plus fréquentes étaient les antipsychotiques atypiques (APA: 10,8%), l'atomoxétine (ATX: 5,5%) et la clonidine (5,3%). Les catégories pour lesquelles les changements se faisaient le plus souvent étaient d'autres stimulants (7,9%), les APA (5,5%) et l'ATX (4,7%). CONCLUSIONS: Environ un enfant/adolescent sur cinq qui souffrent de TDAH et prennent des stimulants ont fait l'expérience d'une thérapie par combinaison ou par changement; toutefois, la majorité des médicaments utilisés en combinaison ou pour le changement n'étaient pas indiqués sur l'étiquette pour le traitement du TDAH au Canada. Ces résultats font ressortir le besoin de plus de recherche pour évaluer les risques-avantages de la combinaison et du changement de stimulants chez les enfants et adolescents souffrant de TDAH.

[The diagnosis of COPD is recommendation dependent]. / Le diagnostic positif de la BPCO est recommendation dépendant.

BACKGROUND: Different spirometric criteria are recommended to diagnosis chronic obstructive pulmonary disease (COPD): -American Thoracic Society/European Respiratory Society (ATS/ERS), Global initiative for chronic Obstructive Lung Disease (GOLD): a post bronchodilator (PBD) ratio between the 1st second Forced Expiratory Volume and Forced Vital Capacity (FEV1/FVC) < 0.70; -Thoracic Society of Australia and New Zealand (ANZTS): a PBD FEV1/FVC < 0.70 and a PBD FEV1 < 80%; -British Thoracic Society (BTS): a before BD (BBD) FEV1/FVC < 0.70 and a BBD FEV1 < 80%; -Old criterion retained, till 2010, by the French Society of Pneumology (SPLF): a PBD ratio between FEV1 and slow vital capacity < 0.70. AIM: To determine, according to the different recommendations, the percentage of smokers having COPD among a population of smokers of more than 40 Packets/Year (PY) addressed for plethysmography. METHODS: The plethysmographic data of 531 consecutive stable male smokers that underwent reversibility testing (400 µg of Salbutamol®) were analyzed. RESULTS: The mean ± SD of age, cigarettes consumption, PBD FEV1 (%), were, respectively, 61 ± 11 Yr, 64 ± 20 PY and 52 ± 21%. The percentages of subjects having COPD according to the above criteria were 75.5% (SPLF old criterion); 71.2% (ATS/ERS, GOLD); 70.8% (BTS) and 69.7% (ANZTS). CONCLUSION: The diagnosis of COPD depends on which guidelines are used for defining the disease. This forms a barrier to early diagnosis, affects public health decisions and wrong planning strategies.

Treatment patterns, resource use, and economic outcomes associated with atypical antipsychotic prescriptions in children and adolescents with attention-deficit hyperactivity disorder in quebec.

OBJECTIVE: To assess treatment patterns, health care resource utilization (HRU), and costs among previously stimulant-treated children and adolescents with attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic (AAP) prescriptions in Quebec. METHODS: Health care claims data extracted from Quebec's provincial health plan database between March 2007 and February 2012 were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking a stimulant and either switched to, or augmented with, an AAP (with the first AAP defined as the index AAP) without a documented diagnosis for which AAPs are Health Canada-approved were included. Discontinuation, augmentation, and switching of the index AAP during the 12-month, follow-up period were estimated using Kaplan-Meier survival analysis. HRU and costs for the 6 months before (baseline period) and after initiation of the index AAP were compared. RESULTS: A total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6 to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation, augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively. Patients had, on average, more all-cause prescription fills (22.2, compared with 13.3) and incurred more all-cause pharmacy ($889, compared with $710), total medical ($1096, compared with $644), and total health care ($1985, compared with $1354) costs during the 6-month study period than during the 6-month baseline period (all P < 0.05). Similarly, ADHD-related total health care costs were higher during the study period ($1269, compared with $835; P < 0.05); all-cause and ADHD-related total health care costs increased by 46.6% and 52.0%, respectively. CONCLUSION: Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs.

Children with Autism and Attention Difficulties: A Pilot Study of the Association between Sensory, Motor, and Adaptive Behaviors.

OBJECTIVES: This pilot study aimed to compare sensory processing, motor skills and adaptive behaviors in children with a double diagnosis of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) (ASD+ADHD) with children with ADHD alone and to examine the association of sensory processing and motor skills with adaptive behaviors (self-care). METHOD: Thirty children aged 5-14 years diagnosed with ASD+ADHD (n = 13) or ADHD (n = 17) were evaluated on their sensory processing and motor skills and adaptive behaviors. Analysis of covariance compared the groups on these dimensions. Correlation analyses examined the association between sensory processing and motor skills and adaptive behaviors. RESULTS: Compared to children with ADHD alone, children with ASD+ADHD had poorer skills in sensory processing (p < 0.001), motor (p = 0.001) and adaptive behaviors (p < 0.001). For all children, increased autonomy in self-care was correlated with better sensory processing (p < 0.001) and motor skills (p = 0.002). CONCLUSION: Children with ASD+ADHD have poorer sensory processing, motor and adaptive skills than those with ADHD alone. Sensory processing and motor deficits were negatively associated with autonomy in self-care. Interventions aiming to improve sensory processing and motor skills and autonomy in self-care should become important targets for these children.

OBJECTIFS: Cette étude pilote visait à comparer les habiletés de traitement de l'informaiton sensorielle, la motricité et les comportments adaptatifs d'enfants avec un double diagnostic de trouble du spectre autistique (TSA) et de trouble de l'attention avec hyperactivité (TSA + TDAH) à des enfants avec un diagnostic simple de TDAH et étudier l'association entre les habiletés de traitement de l'information sensorielle et de motricité avec les comportements adaptatifs (soins personnels). MÉTHODE: Trente enfants âgés de 5 à 14 ans avec un diagnostic de TSA + TDAH (n = 13) ou de TDAH (n = 17) ont été évalués sur le plan des habiletés sensorielles, de la motricité et de leurs comportements adaptatifs. Des analyses de covariance ont comparés les groupes sur ces 3 aspects. Des analyses de corrélations ont documenté l'association entre les habiletés de traitement de l'information sensorielle, la motricité et les complortements adaptatifs. RÉSULTATS: Comparé aux enfants avec un TDAH uniquement, les enfants avec un double diagnostic de TSA + TDAH avaient des habiletés de traitement de l'information sensorielle (p < 0.001), de motricitité (p = 0.001) et des comportements adaptatifs (p < 0.001) plus faibles. Pour tous les enfants, une augmentation de l'autonomie dans les soins personnels était corrélée à de meilleures habiletés de traitment de l'information sensorielle (p < 0.001) et de motricité (p = 0.002). CONCLUSION: Les enfants avec un TSA+TDAH combiné ont de plus faibles habiletés de traitement de l'information sensorielle, de motricité et de comportements adaptatifs que les enfants avec un TDAH uniquement. Les difficultés sensorielles et motrices étaient négativement associées à l'autonomie dans les soins personnels. Des interventions visant à améliorer les habiletés de traitement de l'information sensorielle, la motricité et l'autonomie dans les soins personnels devraient devenir des cibles importantes pour ces enfants.

Antipsychotics in pediatric and adolescent patients: a review of comparative safety data.

BACKGROUND: Over the past few years, prescriptions of antipsychotic medications to children and adolescents have risen significantly. In particular, there is increasing use of second- and third-generation antipsychotic agents. However, numerous studies have shown clinically-relevant adverse effects (such as weight gain, metabolic disorders, prolactin changes, and extrapyramidal symptoms [EPS]) with these therapeutic agents. Moreover, only a few studies have systematically assessed antipsychotics' safety in the pediatric population. The objective of this article is to provide a comparative review of the safety data available for antipsychotic drug use in pediatric populations. METHODS: A PubMed/MEDLINE search was performed for clinical studies that assessed the safety and tolerability of first-generation (typical) and second- and third-generation antipsychotics in children and adolescents with schizophrenia or bipolar disorder. RESULTS: At standard doses, olanzapine and risperidone cause significant weight gain and related metabolic complications in patients treated with the medications. Quetiapine and ziprasidone display a better tolerability profile than risperidone and olanzapine in terms of weight gain, glucose metabolism, increases in prolactin levels, and EPS, while aripiprazole seems to be the most weight-neutral. LIMITATIONS: Most of the studies reviewed had a small sample size, a relatively short duration, and a mixed diagnosis population. Systematic analyses of antipsychotics' safety in young populations are lacking. CONCLUSIONS: The selection of antipsychotics for children and adolescents should include an evaluation of their individual therapeutic benefits, safety profiles, and approval status for use in the pediatric population. Further research of large samples and long-term follow-ups of these patient groups are warranted to help predict/manage the occurrence of adverse effects.

Age-dependent metabolic effects of second-generation antipsychotics in second-generation antipsychotic-naïve French Canadian patients.

BACKGROUND: Patients receiving second-generation antipsychotics (SGAs) may experience secondary metabolic effects such as weight gain, as well as changes in lipid and glucose metabolism. These effects are well documented in adults; however, fewer studies are available concerning their occurrence and their evolution in children and adolescents. OBJECTIVE: The aim of this study was to determine if there is an age-dependent variation in the metabolic effects of SGAs in a drug-naïve population. METHODS: Charts of 232 French Canadian patients participating in a program monitoring the metabolic effects of SGAs were retrospectively reviewed. A total of 85 SGA-naïve patients were selected, including 58 youths and 27 adults. Changes, relative to baseline, in weight, body mass index, lipid metabolism (total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride), and fasting blood glucose were assessed, with follow-up at 3, 6, 12, and 24 months. RESULTS: With respect to weight gain, in both the youth and adult groups, body mass index significantly increased from baseline at 3 months (10.1% [p < 0.0001] and 12.2% [p < 0.0001], respectively) and 6 months (11.8% [p < 0.0001] and 13.1% [p < 0.0001], respectively). With respect to lipid metabolism, in the youth group, there was no significant change. In the adult group, there was a significant increase at 3 and 6 months in total cholesterol (24.0% [p = 0.004] and 24.1% [p = 0.0006], respectively), low-density lipoprotein (26.8% [p = 0.019] and 30.1% [p = 0.010], respectively), and high-density lipoprotein (10.2% [p = 0.04] and 17.1% [p = 0.005], respectively). There was no significant change in triglyceride and glucose metabolism in both groups. CONCLUSIONS: Our results confirm the age-independent effects of SGA on weight gain. However, more data are needed to explore the age effect on glucose and lipid metabolism.

Factor structure of the restricted academic situation scale: implications for ADHD.

BACKGROUND: To study the factor structure of the Restricted Academic Situation Scale (RASS), a psychometric tool used to assess behavior in children with ADHD, 117 boys and 21 girls meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD and aged between 6 and 12 years were recruited. Assessments were carried out before and 65 min after the administration of either a placebo or 0.25 mg/kg of methylphenidate. Placebo and methylphenidate were each administered according to a double-blind placebo-controlled crossover design. RESULTS: Principal component analysis, followed by a confirmatory maximum likelihood factor analysis, revealed two main factors for the RASS, task disengagement (TD) and motor activation (MA). Only TD was inversely correlated with age, indicating that TD and MA may be differentially modulated during development. CONCLUSIONS: MA and TD are distinct traits of ADHD. It may be important to consider them separately when conducting studies on ADHD.

COMT Val108/158Met gene variant, birth weight, and conduct disorder in children with ADHD.

OBJECTIVE: In a recent study, Thapar and colleagues reported that COMT "gene variant and birth weight predict early-onset antisocial behavior in children" with attention-deficit/hyperactivity disorder. We have attempted to replicate these findings in a group of ADHD children using a similar research design. METHOD: Children (n=191) between 6 and 12 years of age who were diagnosed with ADHD were included in the study. Conduct disorder was diagnosed according to DSM-IV criteria based on clinical evaluation and a structured interview (Diagnostic Interview Schedule for Children-IV). The mother's report on the child's birth weight was used in the analysis. Logistic regression analysis, with genotype and birth weight as independent variables and DSM-IV conduct disorder as the dependent variable, was conducted. RESULTS: No significant main effects of genotype and birth weight or interaction effects on conduct disorder were observed. CONCLUSION: In this sample of children diagnosed with ADHD, we find no association between the COMT ValMet gene variant, birth weight, and conduct disorder. Further investigations are required before using birth weight and COMT genotype as predictors of conduct disorder in children with attention-deficit/hyperactivity disorder, especially given the societal and legal ramifications of conduct disorder.

Sleep and COMT polymorphism in ADHD children: preliminary actigraphic data.

OBJECTIVE: To examine whether COMT (catechol-O-methyltransferase) polymorphism modulates aspects of sleep in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). METHOD: Nightly sleep actigraphic recordings during a double-blind, placebo-controlled, crossover clinical study (1 week of 0.5 mg/kg MPH; 1 week of placebo) were obtained for 34 children, 7.4 to 12 years old, diagnosed with ADHD (DSM-IV). Diagnosis was generated by the Diagnostic Interview Schedule for Children and was confirmed by multidisciplinary consensus. RESULTS: Children who were Val allele carriers had poorer sleep continuity compared with children with the Met-Met genotype while receiving a placebo and while receiving methylphenidate. CONCLUSIONS: The findings of the present study support the hypothesis that sleep disturbances in children with ADHD are related to the underlying pathophysiology of the disorder.

Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings.

OBJECTIVES: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature. METHODS: We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montreal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil-Sjostrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD. RESULTS: The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT. CONCLUSIONS: These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD.

Catechol-O-methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD.

BACKGROUND: An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. METHODS: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. RESULTS: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. CONCLUSIONS: Contrary to the observed association between WCST performance and the Val108/158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD.

Sensitivity of tests to assess improvement in ADHD symptomatology.

OBJECTIVE: To assess which measurements best predict improvement on ADHD symptomatology after medication is given. METHODS: 147 children aged 6 to 12 years, diagnosed with ADHD, participated in a double-blind placebo controlled twoweek crossover trial of methylphenidate. RESULTS: There were statistically significant differences on all measures between placebo and medication. Effect size for the overall group was 0.33 (CGI-P), 0.80 (CGI-T), 1.33 (CGI), 0.56 (CPT), 0.82 (RASS). CONCLUSIONS: Acute behavioural response measures, where children are observed by clinicians (RASS and CGI), were overall more reliable than parent reports in detecting improvement on ADHD symptomatology. Teacher reports were also very important, especially in the 9 to 12 year old group.