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Aims Early identification of patients likely to die after acetaminophen (APAP) poisoning remains challenging. We sought to compare the sensitivity and time to fulfilment (latency) of established prognostic criteria. Methods Three physician toxicologists independently classified every in-hospital death associated with APAP overdose from eight large Canadian cities over three decades using the Relative Contribution to Fatality scale from the American Association of Poison Control Centres. The sensitivity and latency were calculated for each of the following criteria: King's College Hospital (KCH), Model for End Stage Liver Disease (MELD) ≥33, lactate ≥3.5 mmol/L, phosphate ≥1.2 mmol/L 48+ hours post-ingestion, as well as combinations thereof. Results A total of 162 in-hospital deaths were classified with respect to APAP as follows: 26 Undoubtedly, 40 Probably, 27 Contributory, 14 Probably not, 25 Clearly not, and 30 Unknown. Cases from the first three classes (combined into n = 93 "APAP deaths") typically presented with supratherapeutic APAP concentrations, hepatotoxicity, acidaemia, coagulopathy and/or encephalopathy, and began antidotal treatment a median of 12 hours (IQR 3.4-30 h) from the end of ingestion. Among all patients deemed "APAP deaths", meeting either KCH or lactate criteria demonstrated the highest sensitivity (94%; 95% CI 86-98%), and the shortest latency from hospital arrival to criterion fulfilment (median 4.2 h; IQR 1.0-16 h). In comparison, the MELD criterion demonstrated a substantially lower sensitivity (55%; 43-66%) and longer latency (52 h; 4.4-∞ h, where "∞" denotes death prior to criterion becoming positive). Conclusions Meeting either KCH or serum lactate criteria identifies most patients who die from acetaminophen poisoning at or shortly after hospital presentation.

Spiritual well-being appears to contribute to mental health and adaptation in adults with acquired brain injury (ABI). ABI-related interventions, including those associated with spirituality, must be specifically designed with learning-related impairments in mind. We conducted a feasibility study of a manualized intervention to support spiritual well-being after ABI called Grace Notes. The goal is to provide clients with time tested, easily accessible spiritual practices that help them experience deeper feelings of being in relationship with their Higher Power as they understand it. Findings suggest that Grace Notes can be implemented by both its developer with the context of an interdisciplinary outpatient rehabilitation program and a rehabilitation clinician as a stand-alone group. People with ABI appear to be interested in a spiritually intervention that draws from a variety of spiritual practices and traditions. Further study related to the efficacy of spiritual well-being intervention after ABI is warranted.

Objectives Guidelines recommend parent management training in the multi-modal treatment of attention deficit hyperactivity disorder (ADHD). The availability of such interventions in Japan is limited. This study evaluated the effects of Well Parent Japan, a hybrid intervention including a group Japanese language adaptation of the New Forest Parenting Programme for ADHD (NFPP) augmented with strategies to improve parent’s psychological wellbeing and enhance confidence in their ability to implement change. Methods Mothers of children aged 6–12 years displaying marked symptoms of ADHD were randomly assigned to the intervention (n = 28) or a waitlist control condition (n = 24). Measures were completed at baseline and again 14 weeks later. Parenting stress was the primary outcome. Other outcomes included maternal depression, parenting self-efficacy, reported and observed parenting behaviour, and maternal ratings of child ADHD, oppositional defiant disorder (ODD) symptoms, and internalizing problems. Results Analysis of covariance (ANCOVA) compared the groups post intervention. Intervention mothers reported significantly less parenting stress, higher parenting self-esteem and use of more effective parenting strategies compared with controls, including a reduction in observed negative parenting, post intervention. These mothers also reported lower levels of child aggression and internalizing problems post intervention together with a trend (p Conclusions Well Parent Japan is an effective psychosocial intervention for parents of children with ADHD in Japan. The group format and the session content is well tolerated. This is the first randomized control trial (RCT) of a psychosocial intervention targeting ADHD in Japan.

International practice guidelines recommend medication and behavioral intervention as evidenced-based treatments for attention deficit hyperactivity disorder (ADHD). Currently in Japan, the availability of non pharmacological interventions for ADHD is limited. We report the results of a pilot and a proof-of-concept study for a new behavioral intervention for Japanese mothers of children with ADHD. The pilot study delivered a standard six-session behavioral intervention and two parent-support sessions. Participants approved the group format and requested additional support to change parenting practices and behavioral strategies targeting ADHD symptoms. For the proof-of-concept study, the intervention was revised to include five sessions of pre intervention support followed by six sessions of the New Forest Parent Training Programme (NFPP), an evidence based intervention for ADHD. The revised intervention, NFPP-Japan, was associated with reductions in the mothers’ reports of children's ADHD symptoms and aggression, more effective parenting practices, and reduced parenting stress. The pilot and proof-of-concept studies indicate that it is possible to successfully modify Western behavioral interventions for Japanese mothers and to justify a randomized controlled trial evaluation of the NFPP-Japan, which is currently underway.

It is unclear if impairments in social functioning and peer relationships significantly differ across common developmental conditions such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and associated callous–unemotional traits (CU traits). The current study explored sex differences and symptoms of parent- and teacher-reported psychopathology on peer relationships and prosocial behaviour in a sample of 147 referred children and adolescents (aged 5–17 years; 120 m). The results showed that increases in parent-reported ADHD Inattentive symptoms and teacher-reported ADHD Hyperactive–Impulsive symptoms, CD, ODD, and CU traits were significantly associated with peer relationship problems across sex. At the same time, teacher-reported symptoms of ODD and both parent- and teacher-reported CU traits were related to difficulties with prosocial behaviour, for both boys and girls, with sex explaining additional variance. Overall, our findings show a differential association of the most common disruptive behaviours to deficits in peer relationships and prosocial behaviour. Moreover, they highlight that different perspectives of behaviour from parents and teachers should be taken into account when assessing social outcomes in disruptive behaviours. Given the questionable separation of conduct problem-related constructs, our findings not only point out the different contribution of those aspects in explaining peer relationships and prosocial behaviour, but furthermore the variance from different informants about those aspects of conduct problems.

Background Preschool hyperactivity is an early risk factor for adult mental health problems and criminality. Little is known about; (a) the patterns of long-term service costs associated with this behavioural marker in the general population and (b) the specific factors predicting hyperactivity-related costs. We undertook a prospective study investigating associations between preschool hyperactivity and average individual annual service costs up to late adolescent and young adulthood. Methods One-hundred and seventy individuals rated as hyperactive by their parents and 88 nonhyperactive controls were identified from a community sample of 4,215 three years olds. Baseline information about behaviour/emotional problems and background characteristics were collected. At follow-up (when individuals were aged between 14 and 25 years) information was obtained on service use, and associated costs since the age of three. Based on this information we calculated the average cost per annum incurred by each individual. Results Compared to controls, preschoolers with hyperactivity had 17.6 times higher average costs per annum across domains (apart from nonmental health costs). These were £562 for each hyperactive individual compared with £30 for controls. Average annual costs decreased as a function of age, with higher costs incurred at younger ages. The effects of hyperactivity remained significant when other baseline factors were added to the model. Effects were fully mediated by later psychiatric morbidity. When the hyperactive group were examined separately, costs were consistently predicted by male gender and, for some cost codes, by conduct problems. Conclusions Preventative approaches targeting early hyperactivity may be of value. Services should be targeted towards high-risk individuals with careful consideration given to the cost-to-benefit trade-off of early intervention strategies.

Objective: To compare the efficacy and cost of specialised individually-delivered parent training (PT) for preschool children with attention-deficit/ hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). Design: Multi-centre, three-arm parallel group randomised controlled trial. Research Setting: National Health Service Trusts. Participants: Preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. Interventions: New Forest Parenting Programme (NFPP) – 12 week individual, home-delivered ADHD PT programme; Incredible Years (IY) – 12 week group-based, PT programme initially designed for children with behaviour problems. Main outcome measures: Primary outcome - Parent ratings of child’s ADHD symptoms (Swanson, Nolan & Pelham Questionnaire - SNAP-IV). Secondary outcomes - teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post-treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputation). Intervention and other costs were estimated using standardized approaches. Results: NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms (mean difference -0.009 95%CI [-0.191, 0.173], p=0.921) or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms (-0.189 95%CI [-0.380, 0.003], p=0.053). NFPP significantly reduced parent-rated conduct-problems compared to TAU across scales (p-values.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1,591 versus £2,103). \ud Conclusions: Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually-delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches. \ud Funding: National Institute of Health Research. \ud Trial Registration: Trial name: COPPI Trial; ISRCTN39288126.

Background: Behavioural interventions are recommended for use with children and young people with ADHD, however specific guidance for their implementation based on the best available evidence is currently lacking. Methods: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. Results: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children’s emotional, social and academic functioning – although most studies have not used blinded outcomes. Generic as well as specialised ADHD parent training approaches - delivered either individually or in groups – have reported beneficial effects. High quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. Conclusion: Parent training is an important part of the multi-modal treatment of children with ADHD which improves parenting, reduces levels of oppositional and non-compliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use it seems important to acknowledge and respond to parental treatment preferences. ispartof: Journal of Child Psychology and Psychiatry vol:59 issue:9 pages:932-947 ispartof: location:England status: published

The New Forest Parenting Programme (NFPP) is a parenting program developed for parents who have a child with attention-deficit hyperactivity disorder (ADHD). It is a manualized program that is delivered in a parent's home over 8 weeks, or in a group format, or through a self-help manual. Three randomized controlled trials have been carried out in the United Kingdom. The NFPP group has adapted the program according to feedback from parents and therapists, and for use with different populations, both within the United Kingdom and internationally. The first international trial took place in New York, United States. Trials in Denmark, Hong Kong, and Japan followed. More recently, a trial of the self-help manual has been carried out in mainland China. This paper will outline the adaptions that were needed in order to be able to deliver the program in different countries with their own expectations of parenting, culture, and language. Training had to be differently focused; manuals and handouts had to be revised, translated and back-translated; and supervision had to be delivered at a distance to maintain the fidelity of the program. The international group will outline their experience of running trials in their own countries with the NFPP in a face-to-face format (Denmark), a group format (Hong Kong and Japan), and a self-help format (mainland China).

Background The importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low ‘take-up’ and high ‘drop-out’ rates compromise the effectiveness of such programmes within the community. Methods This qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. Results and conclusions Many of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented.

Evidence of continuities between preschool hyperactivity and adult mental health problems highlights the potential value of targeting early identification and intervention strategies. However, specific risk factors are currently unclear. This large-scale prospective longitudinal study aimed to identify which hyperactive preschoolers are at the greatest long-term risk of poor mental health. One hundred and seventy children (89 females) rated as hyperactive by their parents, and 88 non-hyperactive controls (48 females) were identified from a community sample of 4215 3-year-olds. Baseline data relating to behavioral/emotional problems and background characteristics were collected. Follow-up mental health and functional impairment outcomes were collected between 14 and 25 years of age. At age 3 years, males and females in the hyperactive group had similarly raised levels of hyperactivity and other behavior problems. In adolescence/young adulthood, these individuals showed elevated symptoms of ADHD, conduct disorder, mood disorder, anxiety and autism, as well as functional impairment. Preschool hyperactivity was strongly predictive of poor adolescent/adult outcomes for males across domains with effects being specifically driven by hyperactivity. For females, the effects of preschool hyperactivity were smaller and dropped to non-significant levels when other preschool problems were taken into account. Environmental risk factors also differed between the sexes, although these may also have been mediated by genetic risk. In conclusion, these results demonstrate marked sex differences in preschool predictors of later adolescent/adult mental health problems. Future research should include a measure of preschool inattention as well as hyperactivity. The findings highlight the potential value of tailored approaches to early identification strategies.

Objective: The current study introduces the Parental Emotional Response to Children Index (PERCI), a new questionnaire specifically designed to measure parents’ emotional response to ADHD and related behaviors (delay discounting and delay aversion). Method: The PERCI was completed by parents of 6- to 14-year-old children with ( n = 126) and without ( n = 160) ADHD. Results: Factor analysis confirmed five separate subscales with acceptable psychometric properties. Parents of children with ADHD reported a stronger emotional response to ADHD behaviors than parents of typically developing children and inattention symptoms evoked the strongest emotional response in parents regardless of child diagnostic status. Conclusion: Parents’ emotional responses appear to be differentiated in terms of specific ADHD-related triggers mapping onto the different domains of ADHD and delay-related responses. Further research is required to understand changes in parental emotional responses over time and their impact on children’s developmental trajectories.

Clinical decision making is influenced by a range of factors and constitutes an inherently complex task. Here we present results from the decisions regarding ADHD management (DRAMa) study in which we undertook a thematic analysis of clinicians' experiences and attitudes to assessment, diagnosis and treatment of ADHD. Fifty prescribing child psychiatrists and paediatricians from Belgium and the UK took part in semi-structured interviews about their decisions regarding the assessment, diagnosis and treatment of ADHD. Interviews were transcribed and processed using thematic analysis and the principles of grounded theory. Clinicians described the assessment and diagnostic process as inherently complicated and requiring time and experience to piece together the accounts of children made by multiple sources and through the use of varying information gathering techniques. Treatment decisions were viewed as a shared process between families, children, and the clinician. Published guidelines were viewed as vague, and few clinicians spoke about the use of symptom thresholds or specific impairment criteria. Furthermore, systematic or operationalised criteria to assess treatment outcomes were rarely used. Decision making in ADHD is regarded as a complicated, time consuming process which requires extensive use of clinical impression, and involves a partnership with parents. Clinicians want to separate biological from environmental causal factors to understand the level of impairment and the subsequent need for a diagnosis of ADHD. Clinical guidelines would benefit from revisions to take into account the real-world complexities of clinical decision making for ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by problems with attention, impulsivity, and hyperactivity. The diagnosis derives from 18 symptoms indexing these behavioural domains [American Psychiatric Association (APA), DSM-IV-TR, 2000]. There is substantial continuity in maintaining a diagnosis of ADHD from childhood to adolescence (Faraone, Biederman, & Mick, 2006); however the phenotypic expression is highly variable within the diagnosed group and across time (Barkley, 2006; Nigg, 2006). Current diagnostic formulations distinguish between symptoms of inattention and those of hyperactivity-impulsivity. Three ADHD subtypes are recognized in the DSM-IV: the predominantly inattentive type, the predominantly hyperactive-impulsive type, and the combined type (where patients meet criteria on both the inattention and the hyperactive/impulsivity domains). This formulation is currently under review as part of the deliberation of the DSM-5 panel. Indeed, this current characterization remains controversial (Barkley, 2001; Diamond, 2005; Hinshaw, 2001; Lahey, 2001; Milich, Balentine, & Lynam, 2001). Here we focus on factor models of co-occurrence among ADHD symptoms. Two major types of factor models, correlated factor models and hierarchical models, have been used to examine coherence and distinctness among ADHD symptom domains. Hierarchical models provide a way to simultaneously conceptualize both the coherence and separability of symptoms from separate domains. These models include a single general factor accounting for covariation among all symptoms along with separate, specific factors of inattention, hyperactivity, and impulsivity that vary orthogonally from the general factor. These models are also termed as bifactor models in the statistical literature. Hierarchical models are different from correlated factor models that only have factors for the symptom domains of inattention and hyperactivity and/or impulsivity (see Figure 1). Several studies have shown hierarchical models with a general factor as having a better fit than correlated models for reported symptoms of ADHD (e.g., Dumenci, McConaghy, & Achenbach, 2004; Gibbins et al., in press; Martel, Von Eye, & Nigg, 2010; Toplak et al., 2009). These papers span clinical and community samples, and child, adolescent, and adult samples with ADHD. A one-factor model has also been considered, but thus far it has no empirical support (Dumenci et al., 2004). Figure 1 Generic example of a correlated two-factor model for 10 observed symptoms Hierarchical models explicitly acknowledge the common covariation among all ADHD symptoms, which is consistent with the conceptualization of ADHD as a single disorder. There are several lines of evidence suggesting that there is substantial commonality between the domains of inattention and hyperactivity-impulsivity. Inattentive symptoms tend to be more highly correlated with hyperactivity and impulsivity than with other domains of psychopathology (Adams, Kelley, & McCarthy, 1997; Conners, 2008; Strickland et al., 2011), with the exception of oppositional defiant disorder in some studies (Lahey et al., 2008). Current models of ADHD also highlight how the symptom domains of inattention, hyperactivity, and impulsivity likely interact to give rise to the heterogeneous expression of ADHD (Nigg & Casey, 2005; Sagvolden, Johansen, Aase, & Russell, 2005; Sonuga-Barke, 2005; Sonuga-Barke, Sergeant, Nigg, & Willcutt, 2008). To replicate and extend these findings, the current study examined different factor models in a large sample of ADHD patients recruited from a broad age range and from diverse national groupings. We were thus able to test whether a hierarchical model held for the whole sample and whether it also was invariant across different age groups and nationalities. A developmental perspective is important to integrate into models of individual ADHD symptoms, such that a single set of factors could parsimoniously explain the changes that occur over development. Age differences in scores from ADHD measures may reflect true differences in the constructs being measured or may simply reflect measurement differences due to age. Therefore, establishing measurement invariance across age groups is important. The behavioural presentation of ADHD changes considerably from childhood to adolescence. For instance, the expression of hyperactivity seems to decrease from childhood to adolescence and inattention commonly appears later in development than hyperactivity and impulsivity (Biederman et al., 2000; Hart et al., 1995; Larsson et al., 2006; Nigg, 2006). This developmental change introduces complex issues with respect to diagnosis. Subtypes have been used to characterize these different symptom presentations, and the instability of ADHD subtypes in developmental samples has also been well demonstrated (Lahey, Pelham, Loney, Lee, & Willcutt, 2005; Todd et al., 2008). Some of this instability of subtypes may be attributable to measurement variability (Lahey et al., 2005; Valo & Tannock, 2010); however some of this variability would be expected from a developmental perspective, which would presume that children’s symptom presentations change over the course of development. What is needed is a coherent model that can represent these shifts and changes in symptoms. In addition to the question of developmental change and continuity in ADHD symptoms, the current sample also had the unique characteristic of having recruited participants from seven European countries and Israel by 12 different research centers. Most studies examining cross-national samples have been concerned with whether there are comparable rates of prevalence across different countries (Faraone, Sergeant, Gillberg, & Biederman, 2003; Polanczyk, de Lima, Horta, Biederman, & Rohde, 2007) rather than consistency in symptom patterns across countries. In addition to testing the five different factor models in the full sample, invariance analyses were also conducted to examine consistency of the best overall model across countries. Thus, in the current study we first estimated five different factor models to determine which model best accounted for ADHD symptoms pooling all ages and locations using a sample of children and adolescents with ADHD and their siblings. The five factor structures included: a) a one-factor model of inattention/ hyperactivity/impulsivity; b) a non-hierarchical two-factor model with correlated inattention and hyperactivity/impulsivity factors (the correlated 2-factor model); c) a non-hierarchical three-factor model with correlated inattention, hyperactivity, and impulsivity factors (the correlated 3-factor model); d) a hierarchical model of a general ADHD factor with two specific factors of inattention and hyperactivity/impulsivity (the hierarchical 2-factor model); and e) a hierarchical model of a general ADHD factor with three specific factors of inattention, hyperactivity, and impulsivity (the hierarchical 3-factor model). Based on previous research, we expected that a hierarchical model with a general ADHD factor would provide the best fit to observed ADHD symptoms in both the ADHD and sibling samples and across instruments and informants. We then examined whether these modeled relationships among symptoms are equivalent across different groups by formally assessing measurement invariance in the ADHD group. Group differences in observed scores on measurement instruments can be attributed to true differences on the constructs being measured only if measurement invariance or equivalence holds across groups (e.g., Widaman & Reise, 1997). Based on the best fitting model, we conducted invariance analyses to determine whether the measurement parameters relating the constructs implied by the model to the observed symptoms are equivalent across age groups and locations in the ADHD group.

Objective: We used multi-level modelling of sibling-pair data to disentangle the influence of proband-specific and more general family influences on maternal expressed emotion (MEE) toward children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: MEE was measured using the Five Minute Speech Sample (FMSS) for 60 sibling pairs (aged 5 through 17 years) each comprising one proband with ADHD and one child without ADHD. Questionnaire measures were used to assess child and adolescent conduct and emotional problems and maternal depression and ADHD. Multi-level models partitioned the effects of five MEE components (initial statement [IS], relationship [REL], warmth [WAR], critical comments [CC], and positive comments [PC]) into proband-specific and general family effects. Results: Significant proband-specific effects were confirmed for all MEE components, with higher levels of MEE expressed toward probands with ADHD than siblings without ADHD. For REL, PC, and CC, this effect was explained by comorbid child conduct problems rather than ADHD. Only low WAR was associated with child ADHD itself. Furthermore, only low WAR was related to variations in more general family characteristics, especially levels of maternal depression. Conclusions: MEE toward children with ADHD was influenced by proband-specific factors. For most components, these were driven by comorbid symptoms of conduct problems rather than ADHD itself. WAR was different; it was influenced by both child-specific and more general characteristics of the family. Further studies utilising a longitudinal design are required to establish the direction of causation and extend our understanding of the relationship between EE components and ADHD. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(10):1042-1053.

Objective The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. Method Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. Results Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. Conclusion The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples.

This paper outlines the presentation, aetiology and treatment of attention deficit hyperactivity disorder (ADHD) in pre-school children. A review of current parenting training interventions demonstrates that there is good evidence for their efficacy in reducing symptoms of ADHD in pre-school children, and three interventions are evaluated: The new forest parent training programme (NFPP); the triple P - positive parenting programme and the incredible years parent training programme (IY). The evaluation of the NFPP provides strong evidence demonstrating its effectiveness for pre-school children with ADHD, while the efficacy of the Triple - P and the IY programme have, to date, only been demonstrated on children with conduct problems and co-morbid ADHD. It is suggested that parent training should be the first choice treatment for pre-school children presenting signs of ADHD, and medication introduced only for those children where parent training is not effective. Few moderators of outcome have been identified for these interventions, with the exception of parental ADHD. Barriers to intervention and implementation fidelity will need to be addressed to achieve high levels of attendance, completion and efficacy. The IY programme is a good model for addressing fidelity issues and for overcoming barriers to intervention. The future directions for parent training are also discussed.

International audience; The revised new forest parenting programme (NFPP) is an 8-week psychological intervention designed to treat ADHD in preschool children by targeting, amongst other things, both underlying impairments in self-regulation and the quality of mother–child interactions. Forty-one children were randomized to either the revised NFPP or treatment as usual conditions. Outcomes were ADHD and ODD symptoms measured using questionnaires and direct observation, mothers' mental health and the quality of mother–child interactions. Effects of the revised NFPP on ADHD symptoms were large (effect size >1) and significant and effects persisted for 9 weeks post-intervention. Effects on ODD symptoms were less marked. There were no improvements in maternal mental health or parenting behavior during mother–child interaction although there was a drop in mothers' negative and an increase in their positive comments during a 5-min speech sample. The small-scale trial, although limited in power and generalizability, provides support for the efficacy of the revised NFPP. The findings need to be replicated in a larger more diverse sample.

Background Delay-related motivational processes are impaired in children with Attention Deficit/Hyperactivity Disorder (ADHD). Here we explore the impact of ADHD on the performance of three putative indices of Delay Aversion (DAv): (i) the choice for immediate over delayed reward; (ii) slower reaction times following delay; and (iii) increased delay-related frustration—to see whether these tap into a common DAv construct that differentiates ADHD cases from controls and shows evidence of familiality. Method Seventy seven male and female individuals (age range 6–17) with a research diagnosis combined type ADHD, 65 of their siblings unaffected by ADHD and 50 non-ADHD controls completed three delay tasks. Results As predicted the size of the correlation between tasks was small but a common latent component was apparent. Children with ADHD differed from controls on all tasks (d = .4–.7) and on an overall DAv index (d = .9): The battery as a whole demonstrated moderate sensitivity and specificity. In general, deficits were equally marked in childhood and adolescence and were independent of comorbid ODD. IQ moderated the effect on the MIDA. Scores on the DAv factor co-segregated within ADHD families. Discussion There is value in exploring the broader DAv phenotype in ADHD. The results illustrate the power of multivariate approaches to endophenotypes. By highlighting the significant, but limited, role of DAv in ADHD these results are consistent with recent accounts that emphasize neuropsychological heterogeneity.

Recent studies of gene–environment interplay in psychiatric disorders have highlighted the complex relationship between genetic and environmental influences. Most published studies on attention deficit hyperactivity disorder (ADHD) have focused on prenatal biological ‘environmental pathogens’, and less attention has been paid to the post-natal social environment. This article provides a brief review of the recent interaction and correlation findings between genes and the social environment in relation to ADHD. Some trends have been identified: (1) synergistic gene–environment interactions (GxE) where adverse social factors increase the risk of expression of putative gene alleles, and (2) antagonistic GxE where favourable social factors attenuate the genetic risks. Where possible, the importance of parenting and its implied relevance to ‘resilience’ is highlighted.

The impact of similarity in parent and child characteristics on the quality of parenting is underresearched. The current study examined the interaction between mother and child attention-deficit/hyperactivity disorder (ADHD) symptoms on parenting. Two hypotheses were tested: the similarity-fit hypothesis, which predicted that parent and child similarity will improve parenting, and the similarity-misfit hypothesis, which predicted the opposite. Study 1 examined the associations between maternal and child ADHD symptoms and child-specific rearing attitudes of 95 mothers with school-aged children. In Study 2 this analysis was extended to more objective observer-rated mother–child interaction and maternal expressed emotion in 192 mothers of preschool children. Child ADHD symptoms were associated with negative maternal comments and maternal ADHD symptoms with negative expressed emotion. In both studies maternal ADHD symptoms appeared to ameliorate the effects of child ADHD symptoms on negative parenting. Parental response to children with high ADHD symptoms was more positive and affectionate when the mother also had high ADHD symptoms. The results support the similarity-fit hypothesis and highlight the importance of considering both child and maternal ADHD symptoms in studies of parenting.

Contains fulltext : 69215.pdf (Publisher’s version ) (Closed access) Common disorders of childhood and adolescence are attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). For one to two cases in three diagnosed with ADHD the disorders may be comorbid. However, whether comorbid conduct problems (CP) represents a separate disorder or a severe form of ADHD remains controversial. We investigated familial recurrence patterns of the pure or comorbid condition in families with at least two children and one definite case of DSM-IV ADHDct (combined-type) as part of the International Multicentre ADHD Genetics Study (IMAGE). Using case diagnoses (PACS, parental account) and symptom ratings (Parent/Teacher Strengths and Difficulties [SDQ], and Conners Questionnaires [CPTRS]) we studied 1009 cases (241 with ADHDonly and 768 with ADHD + CP), and their 1591 siblings. CP was defined as > or =4 on the SDQ conduct-subscale, and T > or = 65, on Conners' oppositional-score. Multinomial logistic regression was used to ascertain recurrence risks of the pure and comorbid conditions in the siblings as predicted by the status of the cases. There was a higher relative risk to develop ADHD + CP for siblings of cases with ADHD + CP (RRR = 4.9; 95%CI: 2.59-9.41); p < 0.001) than with ADHDonly. Rates of ADHDonly in siblings of cases with ADHD + CP were lower but significant (RRR = 2.9; 95%CI: 1.6-5.3, p < 0.001). Children with ADHD + CP scored higher on the Conners ADHDct symptom-scales than those with ADHDonly. Our finding that ADHD + CP can represent a familial distinct subtype possibly with a distinct genetic etiology is consistent with a high risk for cosegregation. Further, ADHD + CP can be a more severe disorder than ADHDonly with symptoms stable from childhood through adolescence. The findings provide partial support for the ICD-10 distinction between hyperkinetic disorder (F90.0) and hyperkinetic conduct disorder (F90.1).

Mother and child ADHD symptoms both have a negative effect on parenting. Little is known about how these characteristics interact. In a recent paper, we reported two studies that suggested that maternal ADHD ameliorated the negative effects of child ADHD on negative parenting supporting a similarity-fit hypothesis. The aim of the current paper is to extend this analysis to a sample of mothers and fathers. The study examined the association between child and adult ADHD symptoms on child-specific parenting practices in 278 mothers and 85 fathers from a population-based sample of school-age children. As in the previous study, high levels of ADHD symptoms in mothers ameliorated the negative effects of child ADHD on parenting - supporting the similarity-fit hypothesis. Fathers demonstrated the opposite effect with high levels of ADHD exacerbating the effects of child ADHD - supporting a similarity-misfit hypothesis. The study confirms the important role played by parental ADHD symptoms in parenting while highlighting differences between mothers and fathers in this regard.

Background: Effective implementation of parent training programmes for preschool Attention-Deficit/Hyperactivity Disorder type is constrained by barriers limiting take-up and effective engagement by ‘hard to reach’ and ‘difficult to treat’ families. Method: We describe an evidence-driven adaptation and piloting of an existing empirically supported preschool ADHD parenting programme to address these problems. Results: The New Forest Parenting programme was changed substantially in terms of length; content and delivery on the basis of information gathered from the literature, from parents and practitioners, further modifications were made after the pilot study. Conclusions: The adapted-NFPP is currently being assessed for efficacy in a large multicentre randomized controlled trial.

Patient: Male, 70 Final Diagnosis: Thyroid storm Symptoms: Atrial fibrillation • confusion • hyperthermia • tachycardia Medication: — Clinical Procedure: Intubation • cardioversion Specialty: Critical Care Medicine Objective: Adverse events of drug therapy Background: We report a case of thyroid storm caused by consuming a Chinese herb contaminated with thyroid hormones. Case Report: A 70-year-old man presented to an emergency department after 2 days of nausea, vomiting, and weakness. Three days previously, he had started taking Cordyceps powder and “Flower Man Sang Hung” as recommended by his Chinese physician. Following admission, the patient deteriorated and was eventually diagnosed with thyroid storm complicated by rapid atrial fibrillation requiring cardioversion, intubation, and intensive care admission. The analysis of the Chinese herb “Flower Man Sang Hung” was positive for levothyroxine. The patient was extubated 11 days after admission and discharged to a rehabilitation centre after 17 days of hospitalization. The Chinese medicine physician was informed of the events. Conclusions: Herbal products can be the source of illness, medication interactions, and contamination. Awareness should be raised among Chinese medicine physicians, allopathic physicians, and their patients. Clinicians should also have a low threshold of suspicion to seek laboratory analysis of suspect substances when the cause of the clinical presentation is unclear.

Needle localization breast biopsy (NLBB) is presently the primary means of localizing non-palpable lesions. Disadvantages of NLBB include vasovagal episodes, patient discomfort, and miss rates. Because hematomas naturally fill the cavity after vacuum-assisted breast biopsies (VABB), we hypothesized that ultrasound (US) could be used to find and accurately excise the actual biopsy site of non-palpable breast lesions without a needle. This is a retrospective study from January 2000 to July 2005. Electronic chart review identified patients with non-palpable breast lesions detected by means of mammogram who then underwent lumpectomy via NLBB or the hematoma-directed ultrasound-guided technique (HUG). HUG involved localizing the hematoma with a 7.5-MHz US probe and using the “line of sight” technique straight down toward the chest wall. A block of tissue encompassing the hematoma was then excised. Localization procedures were performed in 186 patients—63 (34%) via needle localization and 123 (66%) via HUG. The previous VABB site in 100% of patients was successfully excised using HUG, 65 of 123 (53%) were benign and 58 of 123 (47%) were malignant; margins were positive in 13 of these 58 (22%). NLBB was successful in 100% of patients, 44 of 63 (70%) were benign and 19 of 63 (30%) were malignant; margins were positive in 14 of these 19 (73%). Margin positivity was significantly higher for NLBB than HUG (P = 0.0001, Fisher Exact). This study suggests that HUG is more accurate in localizing non-palpable lesions than NLBB. By eliminating the additional procedure needed for NLBB, HUG may also be more time- and cost efficient. HUG makes VABB not only a less invasive diagnostic procedure, but also a localization procedure.

The past decade witnessed an increased use of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) in preschool children. However, the reluctance of parents of preschoolers to place their young children on stimulants ( S. H. Kollins, 2004) coupled with the paucity of information regarding the long-term effects of stimulants in preschoolers makes the development and testing of nonpharmacological treatments for preschoolers with ADHD a major public health priority. This article addresses this issue. First, we highlight issues relating to the existence of ADHD in preschoolers as a clinically significant condition and the need for effective treatment. Second, we examine issues related to the use of pharmacological therapies in this age group in terms of efficacy, side effects, and acceptability. Third, we discuss existing nonpharmacological interventions for preschoolers and highlight the potential value of parent training in particular. Finally, we introduce one candidate intervention, the New Forest Parenting Package, and present initial evidence for its clinical value as well as data on potential barriers and limitations.

In this paper we examine the characteristics of preschool attention deficit hyperactivity disorder (ADHD) from both mental disorder and developmental psychopathology points of view. The equivalence of preschool and school-aged hyperactivity as a behavioral dimension is highlighted together with the potential value of extending the use of the ADHD diagnostic category to the preschool period where these behaviours take an extreme and impairing form (assuming age appropriate diagnostic items and thresholds can be developed). At the same time, the importance of identifying pathways between risk and later ADHD is emphasized. Developmental discontinuity and heterogeneity are identified as major characteristics of these pathways. We argue that models that distinguish among different developmental types of early-emerging problems are needed. An illustrative taxonomy of four developmental pathways implicating preschool hyperactivity is presented to provide a framework for future research.

We describe the toxicokinetics of mercury in two twin toddlers poisoned by an East Indian remedy for teething. Succimer (dimercaprosuccinic acid, DMSA) decreased the plasma elimination half-life of mercury by 3-fold in the patient with high exposure; a more modest effect was observed in the other twin. Succimer is a chelation agent used in the treatment of heavy metal intoxication. A water-soluble agent, it increases the urinary excretion of lead and mercury. The drug is rapidly but variably absorbed through the gastrointestinal tract, with peak levels occurring at 1-2 hours. After its absorption, peak mercury excretion through the urine occurs within 2-4 hours. In the poisoned twin sisters, succimer administration led to a mercury plasma elimination half-life of 6 weeks. Although succimer has been used in mercury poisoning in adults and children, the toxicokinetics of mercury have not previously been characterized in either age group. We believe this is the first such description. More studies on the toxicokinetics and dynamics of mercury chelation with succimer in young children are needed to ensure the optimal use of the drug in this population.

Background: The effectiveness of parent training (PT) when delivered as part of specialist tier-two services for preschool AD/HD children has been recently demonstrated. Aims: To assess the effectiveness of the same PT programme when delivered as part of routine primary care by non-specialist nurses. Method: A sample of 89 3-year-old children with preschool AD/HD took part in a controlled trial of an eight-week (one hour a week), health visitor delivered, PT package. Children, allocated randomly to PT (n = 59) and waiting list control (WLC; n = 30) groups, were compared. Results: PT did not reduce AD/HD symptoms. Maternal well-being decreased in both PT and WLC groups. Conclusions: While PT is an effective intervention for preschool AD/HD when delivered in specialized settings, these benefits do not appear to generalize when programme are delivered as part of routine primary care by non-specialist nurses.

Background: The ‘New Forest Parenting Package’ (NFPP), an 8-week home-based intervention for parents of preschoolers with attention-deficit/hyperactivity disorder (ADHD), fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control. Although NFPP has improved parent and laboratory measures of ADHD in community samples of children with ADHD-like problems, its efficacy in a clinical sample, and relative to an active treatment comparator, is unknown. The aims are to evaluate the short- and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior [‘Helping the Noncompliant Child’ (HNC)] in young children with ADHD. Methods: A randomized controlled trial with three parallel arms was the design for this study. A total of 164 3–4-year-olds, 73.8% male, meeting DSM-IV ADHD diagnostic criteria were randomized to NFPP (N = 67), HNC (N = 63), or wait-list control (WL, N = 34). All participants were assessed at post-treatment. NFPP and HNC participants were assessed at follow-up in the next school year. Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment, and by parents. Secondary ADHD outcomes included clinician assessments, and laboratory measures of on-task behavior and delay of gratification. Other outcomes included parent and teacher ratings of oppositional behavior, and parenting measures. (Trial name: Home-Based Parent Training in ADHD Preschoolers; Registry: ClinicalTrials.gov Identifier: NCT01320098; URL: http://www/clinicaltrials.gov/ct2/show/NCT01320098). Results: In both treatment groups, children's ADHD and ODD behaviors, as well as aspects of parenting, were rated improved by parents at the end of treatment compared to controls. Most of these gains in the children's behavior and in some parenting practices were sustained at follow-up. However, these parent-reported improvements were not corroborated by teacher ratings or objective observations. NFPP was not significantly better, and on a few outcomes significantly less effective, than HNC. Conclusions: The results do not support the claim that NFPP addresses putative dysfunctions underlying ADHD, bringing about generalized change in ADHD, and its underpinning self-regulatory processes. The findings support documented difficulties in achieving generalization across nontargeted settings, and the importance of using blinded measures to provide meaningful assessments of treatment effects.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with performance deficits across a broad range of tasks. Although individual tasks are designed to tap specific cognitive functions (e.g., memory, inhibition, planning, etc.), these deficits could also reflect general effects related to either inefficient or impulsive information processing or both. These two components cannot be isolated from each other on the basis of classical analysis in which mean reaction time (RT) and mean accuracy are handled separately. Method: Seventy children with a diagnosis of combined type ADHD and 50 healthy controls (between 6 and 17 years) performed two tasks: a simple two-choice RT (2-CRT) task and a conflict control task (CCT) that required higher levels of executive control. RT and errors were analyzed using the Ratcliff diffusion model, which divides decisional time into separate estimates of information processing efficiency (called "drift rate") and speed-accuracy tradeoff (SATO, called "boundary"). The model also provides an estimate of general nondecisional time. Results: Results were the same for both tasks independent of executive load. ADHD was associated with lower drift rate and less nondecisional time. The groups did not differ in terms of boundary parameter estimates. Conclusion: RT and accuracy performance in ADHD appears to reflect inefficient rather than impulsive information processing, an effect independent of executive function load. The results are consistent with models in which basic information processing deficits make an important contribution to the ADHD cognitive phenotype.

A 39-year-old homeless man was found confused and incoherent after ingesting an estimated total of 200 tablets of various medications. He presented to the emergency department with delirium, tachycardia, clonus and hyperthermia of 38.0°C. His condition worsened rapidly with his temperature rising to 39.9°C despite active cooling. The patient was subsequently sedated, intubated, paralysed and admitted to the intensive care unit, where he remained for 38 days. His initial presentation of a large mixed drug overdose manifested as serotonin syndrome, which had a protracted course complicated by ethanol withdrawal. He eventually stabilised and was transferred to the general ward, and was subsequently discharged from hospital on day 47 with continuing psychiatric care. This case demonstrates the challenges and considerations in diagnosis and management of large mixed drug overdoses where multiple toxidromes overlap.

Contains fulltext : 69677.pdf (Publisher’s version ) (Closed access) A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a high-cost/high-burden disorder. Early detection and intervention may prevent or ameliorate the development of the disorder and reduce its long-term impact. In this article, we set out a rationale for an early detection and intervention program. First, we highlight the costs of the condition and second, we discuss the limitations of the current treatments. We then outline the potential value of an early detection and intervention program. We review evidence on predictors of poor outcomes for early ADHD signs and discuss how these might allow us to target early intervention more cost-effectively. We then examine potential barriers to engagement with at-risk samples. This leads to a discussion of possible intervention approaches and how these could be improved. Finally, we describe the Program for Early Detection and Intervention for ADHD (PEDIA), a 5-year program of research supported by the UK National Institute for Health Research and conducted at the University of Southampton (Southampton, UK), which aims to develop and evaluate a strategy for early intervention.

Contains fulltext : 97437.pdf (Publisher’s version ) (Open Access) BACKGROUND: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures. METHODS: Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures. RESULTS: Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores. CONCLUSIONS: When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

The current scientific and clinical status of preschool attention deficit hyperactivity disorder and its management is reviewed. Recent clinical and neuropsychological research supporting the utility of the construct will be presented along with a critical analysis of diagnostic issues. The published literature on treatment efficacy (both pharmacological and nonpharmacological) will be reviewed with a special focus on the issue of the safety and side effects of psycho-stimulants. The need for early identification and preventative intervention is indicated but caution should be employed in the use of psychostimulants with this age group.

A case of unusual reactions consisting of involuntary abnormal facial movements in a child following exposure to the 5-HT3 receptor antagonists for prophylaxis against chemotherapy-induced vomiting is presented. Potential mechanisms for these reactions are discussed.

Contains fulltext : 80906.pdf (Publisher’s version ) (Closed access) BACKGROUND: Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems; the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT). METHODS: Seven hundred and twenty-eight males between the ages of 5 and 17 with a DSM-IV research diagnosis of combined type ADHD were included in these analyses. Parents and teachers rated children's conduct and emotional problems. Positive maternal expressed emotion (PMEE) was coded by independent observers on comments made during a clinical assessment with the mother based on current or recent medication-free periods. RESULTS: Sensitivity to the effects of PMEE on CP was moderated by variants of the DAT1 and 5HTT genes. Only children who did not carry the DAT1 10R/10R or the 5HTT l/l genotypes showed altered levels of CP when exposed to PMEE. The effect was most marked where the child with ADHD had both these genotypes. For EMO, sensitivity to PMEE was found only with those who carried the DAT1 9R/9R. There was no effect of DRD4 on CP or EMO. CONCLUSION: The gene-environment interactions observed suggested that genetic make-up can alter the degree of sensitivity an ADHD patients has to their family environment. Further research should focus on distinguishing general sensitivity genotypes from those conferring risk or protective qualities.

Contains fulltext : 80353.pdf (Publisher’s version ) (Closed access) It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

Patient perspectives represent an increasingly important focus in clinical trials of medical treatments for pediatric mental health conditions. This paper describes the development and initial testing of a short, easy to complete, condition specific, measure of patients' and their parents' attitudes regarding drugs used for the treatment of their attention-deficit/hyperactivity disorder (ADHD)--the Southampton ADHD Medication Behaviour and Attitudes scale. On the basis of an initial qualitative study and pilot data, subscales were constructed for both the child and parent versions covering perceived costs and benefits of treatment, patient stigma, and resistance to treatment. The parent version had additional subscales for parental stigma, treatment inconsistency, and flexibility. Factor and reliability analysis of data from 356 parents and 123 of their children supported the distinction between these subscale domains. Children were aged between 5 and 18 years (mean age 10.95 years). Parent and child scores were correlated, although as in previous research parents rated ADHD medications as having more benefits and children rated them as having more costs. The Southampton ADHD Medication Behaviour and Attitudes scale represents a useful addition to the growing portfolio of patient-reported outcomes for ADHD treatments. Future research should focus on the scales value in predicting treatment adherence as it impacts on medication effectiveness.

Contains fulltext : 70708.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC). METHODS: Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach. RESULTS: In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described. DISCUSSION: A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.

Background: The dopamine receptor D4 (DRD4) 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G·E) interaction of the DRD4 7-repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-repeat allele differs between ADHD affected and unaffected children. Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7-repeat allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6–17 years. Results: There was some evidence pointing to differential effects of the DRD4 7-repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G·E interactions. Conclusion: Despite the large sample size, no G·E interactions were found. The impact of the DRD4 7-repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in raterspecific behaviors. Keywords: Dopamine receptor D4 gene, attention deficit hyperactivity disorder (ADHD), maternal smoking during pregnancy, gene by environment interaction.

As part of the International Multi-centre ADHD Gene (IMAGE) project we have completed an affected sibling pair study of 142 narrowly defined DSM-IV combined type ADHD proband-sibling pairs. We found suggestive linkage on chromosomes 9 and 16 with non-parametric multipoint peak LOD scores of 2.13 and 3.1 respectively. There have been several previous ADHD linkage scans. The UCLA study (Fisher et al. 2002; Ogdie et al. 2004; Ogdie et al. 2003), the Dutch study (Bakker et al. 2003), the German study (Hebebrand et al. 2006) and the MGH Study (Faraone et al., submitted) applied the affected sib pair (ASP) strategy; the Columbian study used extended pedigrees ascertained from a population isolate (Arcos-Burgos et al. 2004). No linkage was observed on the most established ADHD linked genomic regions from these studies on 5p and 17p. The highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (LOD=3.1) overlapped with data published from UCLA (LOD>1, ~95cM) and Holland (LOD>1, ~100cM). The second highest peak in this study was on chromosome 9q22 at 90cM (LOD=2.13). Both the UCLA study and the German study also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93cM; German LOD=0.68 at 100cM). The overlap of the two main peaks from this study with those from previous studies suggests that true loci linked to ADHD may lie within these regions

Preoperative injection of technetium-99 m sulfur colloid (Tc-99) in the Nuclear Medicine Department for localizing sentinel lymph nodes (SLNs) can be extremely painful for the patient. The difficulties in scheduling and the delay in starting surgery can be frustrating for the patient and the surgeon. We hypothesized that intraoperative injection facilitated by the subareolar technique would obviate the problems associated with preoperative injection.We performed an institutional review board-approved prospective study of patients with operable breast cancer who were candidates for an SLN biopsy from October 2002 to January 2006 at our institution. After induction of general anesthesia, patients underwent a subareolar injection of 1 mCi Tc-99 unfiltered and blue dye. Data comparing preoperative cost were collected.A total of 236 patients had 252 intraoperative SLN procedures. The mean patient age was 57.3 (range, 24-88) years. The mean +/- standard deviation time from injection to incision was 25.5 +/- 16.2 minutes. Identification rate was 96%, and the number of SLNs identified per patient was 1.6 +/- .8. The count of SLN was 60,313 +/- 134,692 with 20% SLN positivity. Tumor staging distribution was standard staging terminology for an in situ cancer (Tis) = 17 with 0% (+) SLN, T1 = 115 with 11% (+) SLN, T2 = 56 with 29% (+) SLN, T3 = 19 with 37% (+) SLN, and T4 = 4 with 50% (+) SLN. Maximum exposure to the surgeon was well below maximum, at 100 microSV/mo. Preoperative injection had an additive charge of $1325 associated with it for imaging, injection, and interpretation of images by physician.Intraoperative subareolar injection of Tc-99 localizes the SLN and avoids the pain, vasovagal events, delays, and cost associated with preoperative procedure.

Contains fulltext : 70183.pdf (Publisher’s version ) (Closed access) Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD.

Contains fulltext : 71540.pdf (Publisher’s version ) (Closed access) There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE sample (chi(1)(2) = 1.82, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD.

Contains fulltext : 70497.pdf (Publisher’s version ) (Closed access) Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-wide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were