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    ABSTRACT: The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task-based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task-based activation patterns. Traditional univariate case-control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto-limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo-parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task-based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2013;
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    ABSTRACT: Depression is commonly co-morbid with obsessive-compulsive disorder (OCD). However, it is unknown whether depression is a functional consequence of OCD or whether these disorders share a common genetic aetiology. This longitudinal twin study compared these two hypotheses. Method Data were drawn from a longitudinal sample of adolescent twins and siblings (n = 2651; Genesis 12-19 study) and from a cross-sectional sample of adult twins (n = 4920). The longitudinal phenotypic associations between OCD symptoms (OCS) and depressive symptoms were examined using a cross-lag model. Multivariate twin analyses were performed to explore the genetic and environmental contributions to the cross-sectional and longitudinal relationship between OCS and depressive symptoms. In the longitudinal phenotypic analyses, OCS at time 1 (wave 2 of the Genesis 12-19 study) predicted depressive symptoms at time 2 (wave 3 of the Genesis 12-19 study) to a similar extent to which depressive symptoms at time 1 predicted OCS at time 2. Cross-sectional twin analyses in both samples indicated that common genetic factors explained 52-65% of the phenotypic correlation between OCS and depressive symptoms. The proportion of the phenotypic correlation due to common non-shared environmental factors was considerably smaller (35%). In the adolescent sample, the longitudinal association between OCS at time 1 and subsequent depressive symptoms was accounted for by the genetic association between OCS and depressive symptoms at time 1. There was no significant environmental association between OCS and later depressive symptoms. The present findings show that OCS and depressive symptoms co-occur primarily due to shared genetic factors and suggest that genetic, rather than environmental, effects account for the longitudinal relationship between OCS and depressive symptoms.
    Psychological Medicine 08/2013;
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    ABSTRACT: Functional inhibitory neural networks mature progressively with age. However, nothing is known about the impact of gender on their development. This study employed functional magnetic resonance imaging (fMRI) to investigate the effects of age, sex, and sex by age interactions on the brain activation of 63 healthy males and females, between 13 to 38 years, performing a Stop task. Increasing age was associated with progressively increased activation in typical response inhibition areas of right inferior and dorsolateral prefrontal and temporo-parietal regions. Females showed significantly enhanced activation in left inferior and superior frontal and striatal regions relative to males, while males showed increased activation relative to females in right inferior and superior parietal areas. Importantly, left frontal and striatal areas that showed increased activation in females, also showed significantly increased functional maturation in females relative to males, while the right inferior parietal activation that was increased in males showed significantly increased functional maturation relative to females. The findings demonstrate for the first time that sex-dimorphic activation patterns of enhanced left fronto-striatal activation in females and enhanced right parietal activation in males during motor inhibition appear to be the result of underlying gender differences in the functional maturation of these brain regions.
    NeuroImage 07/2013;
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    ABSTRACT: The commentary by Arnold (2013) raises a number of interesting issues and speculations about the action of methylphenidate in children with intellectual disability (ID) and associated neurodevelopmental disorders, such as autism spectrum disorders. In our article (Simonoff et al., 2013), we were careful to stick closely to the statistical analysis plan drawn up (and approved by the Data Monitoring Committee) during data collection and prior to any exploratory analysis. However, a number of the issues raised by Arnold warrant further response, with the aim of clarifying the lessons that can reasonably be drawn for clinical practice.
    Journal of Child Psychology and Psychiatry 06/2013; 54(6):703-4.
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    ABSTRACT: BACKGROUND: An earlier randomised controlled trial demonstrated improved treatment engagement in adolescents who received Therapeutic Assessment (TA) versus Assessment As Usual (AAU), following an emergency presentation with self-harm. OBJECTIVES: To determine 2-year outcomes for the same adolescents focusing on frequency of Accident and Emergency (A&E) self-harm presentations and treatment engagement. METHOD: Patients in the TA groups (n=35) and the AAU group (n=34) were followed up 2 years after the initial assessment. Their primary and secondary care electronic records were analysed. RESULTS: There was no significant difference in the frequency of self-harm resulting in A&E presentations between the two groups (OR 0.69, 95% CI 0.23 to 2.13, p=0.53). Treatment engagement remained higher in the TA group than the AAU group. CONCLUSIONS: TA is not associated with a lower frequency of A&E self-harm presentations. The effect of TA on engagement is maintained 2 years after the initial assessment. Interventions to reduce self-harm in adolescents are needed. TRIAL REGISTRATION: ISRCTN 81605131, http://www.controlled-trials.com/ISRCTN81605131/
    Archives of Disease in Childhood 05/2013;
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    ABSTRACT: BACKGROUND: In addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs). METHODS: Children/adolescents with (n=31) and without ADHD (n=32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task. RESULTS: Children with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group. CONCLUSIONS: The findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children.
    Prostaglandins Leukotrienes and Essential Fatty Acids 05/2013;
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    ABSTRACT: BACKGROUND: The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). Method A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. RESULTS: Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects. CONCLUSIONS: The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.
    Psychological Medicine 04/2013;
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    ABSTRACT: Young people with an autism spectrum disorder (ASD) are more likely to have heightened levels of anxiety compared with their typically developing (non-ASD) peers. The reasons for this are poorly understood, and there has been little research investigating the cognitive correlates of anxiety in individuals with ASD. Typically developing youth with anxiety disorders have frequently been found to show an attentional bias toward threatening information. In this study, we examined whether such a bias was also found in young people with ASD and anxiety symptoms. The protocol utilized two versions of the dot-probe paradigm, the first with emotional faces and the second with emotional words. Participants comprised 38 boys with an ASD and 41 typically developing controls aged 10-16 years of age. Those with an ASD displayed higher levels of parent- and child-rated anxiety (both P < 0.001) and depression (P < 0.001) compared with controls. However, there were no significant group differences in attentional bias scores and no significant relationship between anxiety and attentional bias in either the face or word tasks, for either group. Our findings suggest that, for young people with ASD, unlike non-ASD individuals with an anxiety disorder, high levels of anxiety may not be associated with attentional bias to threat. This may indicate that anxiety in ASD has different cognitive correlates from anxiety in the typically developing population. Further conclusions, study limitations, and future directions are discussed. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 03/2013;
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    ABSTRACT: Objectives. To describe the teaching programme of Therapeutic Assessment (TA), a brief intervention at the point of initial assessment for adolescents with self-harm; to describe trainees' preferences and choices regarding their use of specific aspects of TA. Design. This is a comparative study investigating the differences in the TA skills before and after training. This design was chosen to establish whether or not TA training is efficacious. Methods. Twenty-four clinicians volunteered to participate in five half-day TA training sessions. Their scores on the Therapeutic Assessment Quality Assurance Tool (TAQAT, primary outcome measure) were compared before and after training. Satisfaction with training and therapeutic strategy choices as well as ability to perform TA in an RCT were investigated. Results. Clinicians who participated in TA training had significantly increased scores on TAQAT after training. The clinicians who achieved the required quality of TA post assessments were likely to be able to carry out TA in an RCT with high fidelity. In addition, prior to training, significant differences in the quality of assessments as measured by TAQAT were identified depending on the experience of the clinician. This discrepancy was no longer present post training. Therapeutic strategy based on solution-focused brief therapy (SFBT) was the option of choice post training. Conclusions. TA training is feasible and associated with improved quality of self-harm assessment. PRACTITIONER POINTS: • TA is a brief intervention associated with improved treatment engagement. • TA training is feasible and is associated with improved quality of self-harm assessment. • SFBT-based exit is the most commonly used strategy in TA.
    Psychology and psychotherapy. 03/2013; 86(1):70-85.
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    ABSTRACT: The preceding article by Hawton and colleagues reporting on a prospective study of adolescents presenting with self‐harm to Accident and Emergency departments (A&E) is one of the largest epidemiological studies to examine the long‐term outcomes of selfharm in children and adolescents. After a median of 6 years nearly 30% re‐presented to A&E with self‐harm and 1% died, half of those due to likely suicide and the rest mainly due to accidents. It may be that many accidental deaths were also suicides judging from the method of death. In comparison to adults presenting with self‐harm, the absolute risk of suicide was lower despite a high self‐harm repetition rate. Self‐injury by cutting was a strong independent predictor of suicide as was previous psychiatric treatment and previous self‐harm. Finally the eventual method of suicide was different from that used at either the first or the last episode of selfharm. This is at odds with the data generated by adult literature which consistently shows that those with the most violent methods of selfharm, e.g. attempted hanging or shooting, tend to also die using these methods.In summary the field of adolescent self‐harm is of immense importance and requires urgent research to develop our ability to predict those likely to die of suicide, and to offer effective treatment to those at risk. The article by Hawton and colleagues is an important step in our understanding of the risk factors of suicide in those adolescents who present with self‐harm and in highlighting the overlapping nature of self‐injury and self‐poisoning in relation to suicide.
    Journal of Child Psychology and Psychiatry 10/2012;
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