Impaired Executive Function Mediates the Association between Maternal Pre-Pregnancy Body Mass Index and Child ADHD Symptoms

Increasing evidence suggests exposure to adverse conditions in intrauterine life may increase the risk of developing attention-deficit/hyperactivity disorder (ADHD) in childhood. High maternal pre-pregnancy body mass index (BMI) has been shown to predict child ADHD symptoms, however the neurocognitive processes underlying this relationship are not known. The aim of the present study was to test the hypothesis that this association is mediated by alterations in child executive function.A population-based cohort of 174 children (mean age = 7.3 ± 0.9 (SD) yrs, 55% girls) was evaluated for ADHD symptoms using the Child Behavior Checklist, and for neurocognitive function using the Go/No-go task. This cohort had been followed prospectively from early gestation and birth through infancy and childhood with serial measures of maternal and child prenatal and postnatal factors. Maternal pre-pregnancy BMI was a significant predictor of child ADHD symptoms (F((1,158)) = 4.80, p = 0.03) and of child performance on the Go/No-go task (F((1,157)) = 8.37, p = 0.004) after controlling for key potential confounding variables. A test of the mediation model revealed that the association between higher maternal pre-pregnancy BMI and child ADHD symptoms was mediated by impaired executive function (inefficient/less attentive processing; Sobel Test: t = 2.39 (± 0.002, SEM), p = 0.02).To the best of our knowledge this is the first study to report that maternal pre-pregnancy BMI-related alterations in child neurocognitive function may mediate its effects on ADHD risk. The finding is clinically significant and may extrapolate to an approximately 2.8-fold increase in the prevalence of ADHD among children of obese compared to those of non-obese mothers. These results add further evidence to the growing awareness that neurodevelopmental disorders such as ADHD may have their foundations very early in life

Host and Environmental Influences on Development of Disease

While many myxozoan parasites produce asymptomatic infections in fish hosts, several species cause diseases whose patterns of prevalence and pathogenicity are highly dependent on host and environmental factors. This chapter reviews how these factors influence pathogenicity and disease prevalence. Influential host factors include age, size and nutritional state. There is also strong evidence for host strains that vary in resistance to infection and that there is a genetic basis for resistance. A lack of co-evolutionary processes appears to generally underly the devastating impacts of diseases caused by myxozoans when introduced fish are exposed to novel parasites (e.g. PKD in rainbow trout in Europe) or when native fish are exposed to an introduced parasite (e.g. whirling disease in North America). Most available information on abiotic factors relates to water temperature, which has been shown to play a crucial role in several host parasite systems (e.g. whirling disease, PKD) and is therefore of concern in view of global warming, fish health and food sustainability. Eutrophication may also influence disease development. Abiotic factors may also drive fish disease via their impact on parasite development in invertebrate hosts

Fish Immune Responses to Myxozoa

Myxozoans evoke important economic losses in aquaculture production, but there is almost a total lack of disease control methods as no vaccines or commercial treatments are currently available. Knowledge of the immune responses that lead to myxozoan elimination and subsequent disease resistance is vital for shaping the future development of disease control measures. Different fish immune factors triggered by myxozoan parasites are reviewed in this chapter. Detailed information on the phenotypic and underlying molecular aspects of innate and adaptive responses, at both cellular and humoral levels, is provided for some well-studied fishmyxozoan systems. The importance of the local immune response, mainly at mucosal sites, is also highlighted. Myxozoan tactics to disable or avoid immune responses, such as modulation of immune gene transcription and immune evasion, are also reviewed. The existence of innate and acquired resistance to some myxozoan species suggest promising possibilities for controlling myxozooses through immune-based strategies, such as genetic selection for host resistance, vaccination, immune therapies and administration of immunostimulants

Promoting remyelination: utilizing a viral model of demyelination to assess cell-based therapies

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS. While a broad range of therapeutics effectively reduce the incidence of focal white matter inflammation and plaque formation for patients with relapse-remitting forms of MS, a challenge within the field is to develop therapies that allow for axonal protection and remyelination. In the last decade, growing interest has focused on utilizing neural precursor cells (NPCs) to promote remyelination. To understand how NPCs function in chronic demyelinating environments, several excellent pre-clinical mouse models have been developed. One well accepted model is infection of susceptible mice with neurotropic variants of mouse hepatitis virus (MHV) that undergo chronic demyelination exhibiting clinical and histopathologic similarities to MS patients. Combined with the possibility that an environmental agent such as a virus could trigger MS, the MHV model of demyelination presents a relevant mouse model to assess the therapeutic potential of NPCs transplanted into an environment in which inflammatory-mediated demyelination is established