This PhD research project investigated differences in long-chain polyunsaturated fatty acids (LC-PUFA) between male adolescents with and without ADHD, and the relationship between these and performance and event related potential (ERP) assessments of brain function and clinical behavioural measures. ERPs were also investigated in a randomised, double-blind, placebo-controlled clinical trial of 12 weeks PUFA supplementation in ADHD. Comparison of LC-PUFA measures between two groups of ADHD showed no differences in the first group, but in the second group, omega-3/6 indices were lower in ADHD compared to controls. No relationships were observed between LC-PUFA and clinical behaviour measures except between specific omega-3 indices which were inversely related to callous and unemotional traits in the ADHD group only, suggesting a specific relationship with socio-emotional behaviour. Despite performance differences there were no ERP differences between ADHD and controls during the sustained attention task and specific P3 reduction in ADHD for the Go process of the Go/NoGo task. The performance was correlated with LC-PUFA in controls only. Associations were observed between reduced P3 and LC-PUFA in both groups, possibly suggesting enhanced neuronal efficiency. For the emotion processing task, patients showed reduced N2 and N4 amplitudes relative to controls. Omega-3 was associated with more normal N4 function in ADHD for happy faces. The 12 week supplementation trial demonstrated only enhanced P2 to happy faces in the active group relative to placebo at follow up. Overall, the findings demonstrate reduced PUFA blood levels in some groups of ADHD children but limited and very specific associations between fatty acids, clinical measures and brain function in ADHD.

Adolescence represents a time in development when the reward system undergoes substantial changes. Several studies suggest differences in reward processing amongst adolescents compared to adults and children. Abnormalities in reward processing also underlie many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD). The present research has the following objectives: 1) to investigate normal reward processing during reward anticipation and reward feedback in a large population based cohort of old adolescents. 2) to explore gender differences in reward processing and determine whether the association between reward processing and ADHD symptoms differs between boys and girls. 3) to determine whether the X-linked gene Monoamine Oxidase A (MAOA) is associated with ventral striatal brain activation during reward anticipation and 4) to investigate whether MAOA stratifies the relationship between ventral striatal activation and ADHD symptoms in boys. Objectives 1 and 2 were explored using the full IMAGEN dataset (n > 1200 adolescent), objective 3 was addressed using the first wave of IMAGEN, including both boys and girls (n = 411 adolescents) whereas objective 4 was investigated using only boys from the first wave (n = 190 adolescents). The results from random effects analyses and region of interest analyses suggested robust activation patterns during reward anticipation and feedback, particularly in the ventral striatum (VS) and orbitofrontal cortex. Gender differences were prominent during both phases of reward processing with boys showing significantly higher activation of a number of regions, including the VS, relative to girls. We also found that the X-linked gene MAOA significantly affected VS activation in boys, but not in girls. This gene also stratified the frequently reported relationship between VS activation and ADHD symptoms in adolescent boys.

The neuronal ceroid lipofuscinosis (NCLs, Batten Disease) are inherited, fatal neurodegenerative disorders of childhood. In all forms of NCL, astrocyte activation occurs early in the disease and precedes neuronal loss. However, in the most common juvenile form (JNCL), which is caused by a mutation in the Cln3 gene, this astrocyte response appears to be compromised. Since astrocytes are crucial for the functioning and survival of neurons, and emerging evidence highlights the pivotal role that reactive astrocytosis plays in the pathogenesis of CNS diseases, any deficits in the biology of these cells could significantly impact neuronal health. In order to study the functioning of JNCL astrocytes, these cells were isolated from a well-characterised mouse model of the disease, Cln3 deficient mice (Cin3-l- mice), and their basic biology characterised. These studies revealed that Cln3-l- astrocytes have a disrupted actin and intermediate filament cytoskeleton. Possibly due to these defects, Cln3-l- astrocytes have an attenuated ability to response to an activation stimulus, just as observed in vivo, and to divide and migrate. They also display pronounced defects in their ability to take-up glutamate and to secrete a range of proteins, including cytokines, neuroprotective factors and the anti-oxidant glutathione, that become even more evident upon stimulation. Additionally, their impaired calcium signalling suggests that communication might be altered in these cells. Most importantly, using a co-culture system, these Cln3-l- glia were shown to negatively impact the health of both Cln3-l- and wild-type neurons, with the mutant neurons being the most severely affected, probably because of their own compromised biology. This includes a reduction in neurite complexity and displacement of the axon initial segment (AIS), which modulates neuronal excitability and the initiation of axon potentials. Thus, these data show, for the first time, that JNCL astrocytes are functionally compromised and might play an active role in the neurodegeneration observed in JNCL. Further, this information raises the possibility that, in future, astrocytes should be considered as targets for therapeutic interventions.

Background: Childhood obesity in the UK is increasing. Possible explanations are changes in dietary patterns and eating habits together with an increase in sedentary lifestyles. There is evidence that multifaceted school-based interventions have some success in reducing childhood obesity. This study aimed to develop and test the feasibility of a school-based intervention programme aimed to improve children’s lifestyle behaviours and eating habits as a contribution to preventing childhood obesity. Methods: Nine primary schools from highly deprived wards in Bexley took part in a baseline study to collect information on obesity, eating and activity patterns and body shape satisfaction of children aged 9-11. The data were used to produce materials to be used in the schools. The intervention programme involved curriculum-based and extra-curricular activities and was used with 350 children in 4 schools over a 6 month period, with 5 others as controls. A repeat of the baseline study at the end of the intervention period in all schools investigated the effect of the intervention on the eating patterns of children. A further study was undertaken after 1 year to look at the longer term effect of the intervention. Results: Nearly a third of those measured were either overweight or obese. Children exhibited signs of body shape dissatisfaction. About a third of boys and over 40% of girls indicated they wanted to be thinner than their perceived shape. Following the intervention, changes in eating habits found in the intervention schools were increased vegetable intake at the evening meal and reduced consumption of snacks during the day. Positive changes in eating patterns were also seen in all schools between surveys. The intervention did not appear to have any impact on the body shape dissatisfaction of children. Conclusion: The intervention had some impact on improving vegetable intakes and consumption of healthier snacks in children.

Background: Childhood obesity in the UK is increasing. Possible explanations are changes in dietary patterns and eating habits together with an increase in sedentary lifestyles. There is evidence that multifaceted school-based interventions have some success in reducing childhood obesity. This study aimed to develop and test the feasibility of a school-based intervention programme aimed to improve children’s lifestyle behaviours and eating habits as a contribution to preventing childhood obesity. Methods: Nine primary schools from highly deprived wards in Bexley took part in a baseline study to collect information on obesity, eating and activity patterns and body shape satisfaction of children aged 9-11. The data were used to produce materials to be used in the schools. The intervention programme involved curriculum-based and extra-curricular activities and was used with 350 children in 4 schools over a 6 month period, with 5 others as controls. A repeat of the baseline study at the end of the intervention period in all schools investigated the effect of the intervention on the eating patterns of children. A further study was undertaken after 1 year to look at the longer term effect of the intervention. Results: Nearly a third of those measured were either overweight or obese. Children exhibited signs of body shape dissatisfaction. About a third of boys and over 40% of girls indicated they wanted to be thinner than their perceived shape. Following the intervention, changes in eating habits found in the intervention schools were increased vegetable intake at the evening meal and reduced consumption of snacks during the day. Positive changes in eating patterns were also seen in all schools between surveys. The intervention did not appear to have any impact on the body shape dissatisfaction of children.

The aims of the present study were to a) examine gender differences in body image dissatisfaction, disordered eating and drive for muscularity in pre-adolescent children and b) to explore whether children experienced perceptual distortions whilst looking at media imagery. One hundred and ninety one children aged between nine and ten years participated in the study. Levels of body image dissatisfaction were found to be equal amongst boys and girls. However, their expression of body image dissatisfaction differed, in that most girls wished for a thinner body shape, whereas the boys were equally split between those who wished to be thinner and those who wished to be larger. There were no gender differences in levels of eating disturbance. Boys reported a significantly higher drive for muscularity than girls. A significant interaction was found between the gender and the size of media celebrities on the perceptual distortion task. The clinical implications of these findings are discussed. This includes the need for educational work with professionals and children, to raise awareness of the rising prevalence of eating disturbance and body image dissatisfaction in pre-adolescent children and gender differences in their expression. The results of this study also suggest that clinical services may see a rising prevalence of eating disorders and exercise disorders in males. Implications for further research are discussed.

The aim of this paper is to review the research literature on characteristics of narrative in autism in order to specify more clearly the relative abilities and deficits of children with autism in this mode of social communication. The paper first considers how narrative can provide information about the way in which we understand and engage in social exchanges. It then provides a framework for the large body of literature on narrative in typically developing children and this is defined within three parameters of narrative described by Norbury and Bishop (2003). The review considers social communication and pragmatic language in autism before describing in more depth the main studies investigating narrative in autism. It concludes with theoretical implications of narrative ability with autism and reflects upon the value of using narrative as a tool for exploring social understanding.

This review argues that a cognitive bias towards increased vigilance and perception of threat underlies childhood anxiety. It is hypothesised that parents of anxious children inadvertently reinforce this bias, or fail to help children inhibit it. The review explores the literature linking threat perception and anxiety, and considers how such a bias may develop. It is argued that parents of anxious children reinforce threat perception in the way they talk to their children, the behaviour that they model and their style of parenting. As few studies, reviews or models have directly tested these hypotheses, evidence from a range of relevant frameworks is considered.

Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs leading to complement activation and cell lysis. Mutations in MBL promoter and exon-1 result in reduced protein levels and in a number of studies appear to increase susceptibility to infection. This thesis explores the role of MBL in paediatric infection in two clinical settings. The effect of MBL deficiency on susceptibility and progression of HIV-1 infection was investigated in one hundred and twenty eight children, aged 2-16 years. MBL deficiency appeared to be less frequent in this population than in published series of Caucasian or African children. This may be due to selective survival of children with wild type MBL genotypes as patients with severe disease, as assessed by low CD4+T cell counts, were more likely to have MBL variant alleles. In support of this hypothesis, MBL deficiency was less frequent in children classified as long term non- progressors (LTNP-s). A second study explored the impact of MBL on susceptibility and severity of infection in preterm neonates. One hundred sixty six preterm neonates were genotyped for MBL mutations by polymerase chain reaction (PCR) and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A= wild type, 0=variant alleles) and protein levels between groups was performed using Chi-square, Mann-Whitney or Kruskal-Wallis test. Low MBL levels were observed in premature neonates, particularly in the first week of life (p=0.001). MBL deficiency was associated with an increased risk of sepsis in VLBW neonates (<1500g), (p=0.0T). The studies described in this thesis provide support for MBL having a role in susceptibility to and severity of infection in children.

This thesis explores how we as neurotypicals, people who have normal neurological development, might re-perceive every-day tasks and objectives, when faced with a neurodiverse perspective that can contradict neurotypical developments. The term neurodiversity mostly appears within the online autistic community. How Autistic Spectrum Children are able to avoid, deal with or utilise alternative strategies for communication and development is visualised through a series of practical projects. The visualisation of difference informs theoretical and scientific material through narrative illustration. Narration is here considered part of the ubiquitous component of human communication. The ability to process linguistic information and social cueing is observed through verbal communication, body language and social and formal interaction between each other. This prompts reaction, tolerance and an appropriation of cueing and reciprocation. Neurodiversity is, as in any typical neurological development, a human difference that should be tolerated and respected as any other human difference. Acceptance of difference is key to the topics and issues held in the practical work produced in this submission. Semiotic meaning is used in the practical works as part of a general communicative discourse, combining image, codes, signs and symbols that exhibit different modalities that are presented to and decoded by the viewer. Visualy based enquiry allows investigation into the communication difficulties between the Asperger's children and the people that surround them, namely parents, siblings, family members, friends and school associates including staff and peers. The practical projects visualise the difference in the behaviour of the Asperger's child where non-appropriate responses to stimuli are presented. Interviews, meetings and questionnaires present case studies with anonymity; clinical support and parental experiences inform visual developments. This project contributes to the visualisation of scientific data where imaging encourages understanding with the subject. The role of the body of practice submitted is also considered from the perspective of developing and informing pedagogic practice, in parallel with strengthening a personal practitioner base. In all, fourteen projects are reported on, each is disseminated via a website attached to the Portsmouth University Illustration Course website - www. envf. port. ac. uk/illustration/ under my staff name Bob Wright and also at - www. thoughtism. co. uk The simplification of the complexities in multiaxial diagnosis strategies, were a starting point for the project. Medical assessment of ASD children can further confirm any parental suspicions. These parental observations and the important relation and or bearing upon diagnosis are a key issue I have raised in some of the projects.