Prenatal life and post-natal psychopathology: evidence for negative gene-birth weight interaction

BACKGROUND: Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. METHOD: The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. RESULTS: A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. CONCLUSIONS: Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.     

Task-related motivation and academic achievement in children and adolescents with ADHD

European Child & Adolescent Psychiatry - Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which...     

A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD

OBJECTIVE: The aim of this study was to study treatment response to atomoxetine in a large, multicenter study of non-North American patients with ADHD. METHODS: A total of 604 children and adolescents with ADHD were enrolled in a 10-week open-label trial with atomoxetine prior to randomization to a double-blind relapse prevention phase at 33 sites in the United Kingdom, continental Europe, Israel, South Africa, and Australia. All patients had ADHD symptom severity at least 1.5 standard deviations above United States age and gender norms for their diagnostic subtype as measured by the investigator-scored ADHD Rating Scale (ADHD RS). Outcomes were assessed by analysis of change in the ADHD RS; functional and psychosocial outcomes were assessed using the Child Health Questionnaire (CHQ). RESULTS: At endpoint, ADHD RS total scores decreased by an average of 56.7%, and 69% of patients were rated as having no or minimal symptoms. Significant improvement was observed in psychosocial and functional outcomes. Discontinuations attributed to adverse events were < 4%. CONCLUSION: These open-label data, gathered in an international setting, add to our knowledge of the value of atomoxetine in treating ADHD symptoms, as well as its safety and tolerability.     

Are children with ADHD predominantly inattentive and combined subtypes different in terms of aspects of everyday attention?

The validity of the DSM-IV subtypes is a recurring diagnostic debate in attention deficit/hyperactivity disorder (ADHD). Laboratory measures, such as the test of everyday attention for children (TEA-Ch) can help us address this question. TEA-Ch is a test battery covering different aspects of everyday attention relating to selective and sustained attention and attentional control. The aim of the current study was to investigate whether this instrument can differentiate between combined (ADHD-C) and inattentive subtype (ADHD-I) of ADHD. Subjects were recruited from a multidisciplinary ADHD outpatient unit and tested free of medication. Sixty-four children with a diagnosis of ADHD were included (38 with ADHD-C; 26 with ADHD-I). The control group was 76 children recruited from primary and secondary schools. Children with ADHD performed worse than controls on 6 out of 9 TEA-Ch subtests. However a regression analysis revealed that TEA-Ch subtests made only a marginal contribution to the correct classification of ADHD, once the effects of IQ and age are controlled. Confirmatory factor analysis in our ADHD group demonstrated that the three factor structure achieved a poor fit. More detailed analysis suggested that inferior performance on the tasks designed to test vigilance was not the result of deficient-sustained attention. ADHD-C and ADHD-I showed very few differences across tasks. In conclusion, our results provided not much support for the value of the ADHD-C and ADHD-I distinction in predicting difficulties in everyday attention.     

The quality of life of children with attention deficit/hyperactivity disorder: a systematic review

Quality of life (QoL) describes an individual’s subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents’ perspective. QoL outcomes should be included as a matter of course in future treatment studies.     

Practitioner Review: Current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents

Background: Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well‐tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence‐ and expert‐based guidance concerning the management of (AEs) with medications for ADHD. Methods: For ease of use by practitioners and clinicians, the article is organized in a simple question and answer format regarding the prevalence and management of the most common AEs. Answers were based on empirical evidence from studies (preferably meta‐analyses or systematic reviews) retrieved in PubMed, Ovid, EMBASE and Web of Knowledge through 30 June 2012. When no empirical evidence was available, expert consensus of the members of the European ADHD Guidelines Group is provided. The evidence‐level of the management recommendations was based on the SIGN grading system. Results: The review covers monitoring and management strategies of loss of appetite and growth delay, cardiovascular risks, sleep disturbance, tics, substance misuse/abuse, seizures, suicidal thoughts/behaviours and psychotic symptoms. Conclusion: Most AEs during treatment with drugs for ADHD are manageable and most of the times it is not necessary to stop medication, so that patients with ADHD may continue to benefit from the effectiveness of pharmacological treatment.     

Modelling bivariate ordinal responses smoothly with examples from ophthalmology and genetics.

A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of the generalized additive model (GAM) of Hastie and Tibshirani. The original BDM is an example of a bivariate generalized linear model. In this paper smoothing is introduced on the marginal as well as on the association level. Our non-parametric procedure can be used as a diagnostic tool for identifying parametric transformations of the covariates in the linear BDM, hence it also provides a kind of goodness-of-fit test for a bivariate generalized linear model. Cubic smoothing spline functions for the covariates are estimated by maximizing a penalized version of the log-likelihood. The method is applied to two studies. The first study is the classical Wisconsin Epidemiologic Study of Diabetic Retinopathy. The second study is a twin study, where the association between the elements of twin pairs is of primary interest. The results show that smoothing on the association level can give a significant improvement to the model fit.     

Eunethydis: a statement of the ethical principles governing the relationship between the European group for ADHD guidelines, and its members, with commercial for-profit organisations

The Eunethydis ADHD Guidelines group set out here the ethical principles governing the relationship between the group and industry. The principles set out here are provided to ensure that this is both done and seen to be done. The impetus for these guidelines comes from within the Group and is linked to the recognition for the need for an open and transparent basis for Group-industry relations, especially in the light of the present concern that the pharmaceutical industry may be exerting a growing influence on the actions of researchers and clinicians in the ADHD field.     

A randomized, double-blind study of continuation treatment for attention-deficit/hyperactivity disorder after 1 year.

BACKGROUND: The efficacy of atomoxetine in maintaining symptom response following 1 year of treatment was assessed in children and adolescents (n = 163) with DSM-IV defined attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects had previously responded to atomoxetine acutely and had completed 1 year of double-blind atomoxetine treatment. They were then randomly assigned in double-blind fashion to continued atomoxetine or placebo substitution for 6 months. RESULTS: Atomoxetine was superior to placebo in preventing relapse (Wilcoxon test, p = .008) and in maintaining symptom response (ADHD Rating Scale IV score, p < .001). Among subjects assigned to discontinuation, the magnitude of symptom return was generally to a level of severity less than that observed at study entry. CONCLUSIONS: Following 1 year of treatment with atomoxetine, continued treatment over the ensuing 6 months was associated with superior outcomes compared with placebo substitution. However, there was considerable variability between individuals in the magnitude of symptom return after drug discontinuation, suggesting that some subjects treated with atomoxetine for a year with good results may consolidate gains made during drug treatment and could benefit from a medication-free trial to assess the need for ongoing drug treatment.