The development of anxiety disorders in childhood: an integrative review

We present an integrative review of the development of child anxiety, drawing on a number of strands of research. Family aggregation and genetic studies indicate raised vulnerability to anxiety in offspring of adults with the disorder (e.g. the temperamental style of behavioural inhibition, or information processing biases). Environmental factors are also important; these include adverse life events and exposure to negative information or modelling. Parents are likely to be key, although not unique, sources of such influences, particularly if they are anxious themselves. Some parenting behaviours associated with child anxiety, such as overprotection, may be elicited by child characteristics, especially in the context of parental anxiety, and these may serve to maintain child disorder. Emerging evidence emphasizes the importance of taking the nature of child and parental anxiety into account, of constructing assessments and interventions that are both disorder specific, and of considering bidirectional influences.

The longitudinal development of emotion regulation capacities in children at risk for externalizing disorders

The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating: a) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms; and b) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation. Families experiencing high (n=58) and low (n=63) levels of psychosocial adversity were recruited to the study during pregnancy. Direct observational assessments of child emotion regulation capacities and maternal sensitivity were completed in early infancy, at 12 and 18-months, and at 5-years. Key findings were as follows. First, high risk children showed poorer emotion regulation capacities than their low risk counterparts at every stage of assessment. Second, from 12-months onwards, emotion regulation capacities showed a degree of stability, and were associated with behavioral problems, both concurrently and prospectively. Third, maternal sensitivity was related to child emotion regulation capacities throughout development, with poorer emotion regulation in the high risk group being associated with lower maternal sensitivity. The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology, and highlight insensitive parenting as a potentially key developmental influence.

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

Children's representation of family mealtime in the context of maternal eating disorders

Background Recent research provides evidence for specific disturbance in feeding and growth in children of mothers with eating disorders. Aim To investigate the impact of maternal eating disorders during the post-natal year on the internal world of children, as expressed in children's representations of self and their mother in pretend mealtime play at 5 years of age. Methods Children of mothers with eating disorders (n = 33) and a comparison group (n = 24) were videotaped enacting a family mealtime in pretend play. Specific classes of children's play representations were coded blind to group membership. Univariate analyses compared the groups on representations of mother and self. Logistic regression explored factors predicting pretend play representations. Results Positive representations of the mother expressed as feeding, eating or body shape themes were more frequent in the index group. There were no other significant group differences in representations. In a logistic regression analysis, current maternal eating psychopathology was the principal predictor of these positive maternal representations. Marital criticism was associated with negative representations of the mother. Conclusions These findings suggest that maternal eating disorders may influence the development of a child's internal world, such that they are more preoccupied with maternal eating concerns. However, more extensive research on larger samples is required to replicate these preliminary findings.

Cognitive therapy for anxiety disorders: current status and future directions.

This paper reviews recent theoretical, conceptual and practice developments in cognitive-behaviour therapy (CBT) for anxiety disorders. The empirical status of CBT for anxiety disorders is reviewed and recent advances in the field are outlined. Challenges for the future development of CBT for the anxiety disorders are examined in relation to the efficacy, effectiveness and cost-effectiveness of the approach. It is concluded that the major challenge currently facing CBT for anxiety disorders in the UK is how to meet the increased demand for provision whilst maintaining high levels of efficacy and effectiveness. It is suggested that the creation of an evidence base for the dissemination of CBT needs to become a priority for empirical investigation in order effectively to expand the provision of CBT for anxiety disorders.

Sibling interaction of children with autism: development over 12 months

While deficits in social interaction are central to autism, the sibling relationship has been found to provide a key medium for the development of such skills. Naturalistic observations of sibling pairs including children with autism and controls with Down syndrome were made across two time periods, twelve months apart. Consistent with the evidence on typically developing children, the amount and rate of initiations of both prosocial and agonistic interaction increased, but further analysis suggested that these interactions were stage-managed by the typically developing children. Results show social interaction and imitation in children with autism and the special role that sibling interactions can play. Longitudinal research on the acquisition of social skills in children with developmental disabilities is needed.

Cognitive behaviour therapy for eating disorders

The eating disorders provide one of the strongest indications for cognitive behaviour therapy (CBT). This bold claim arises from two sources: first, the fact that eating disorders are essentially cognitive disorders and second, the demonstrated effectiveness of CBT in the treatment of bulimia nervosa, which has led to the widespread acceptance that CBT is the treatment of choice. In this paper the cognitive behavioural approach to the understanding and treatment of eating disorders will be described. A brief summary of the evidence for this account and of the data supporting the efficacy and effectiveness of this form of treatment will be provided. Challenges for the future development and dissemination of the treatment will be identified.

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

Speech perception and phonological short-term memory capacity in language impairment: preliminary evidence from adolescents with specific language impairment (SLI) and autism spectrum disorders (ASD)

Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the contributions of PSTM and speech perception in non-word processing and whether individuals with SLI and ASD plus language impairment (ALI) show similar or different patterns of deficit in these cognitive processes. Method & Procedures: Three groups of adolescents (aged 14–17 years), 14 with SLI, 16 with ALI, and 17 age and non-verbal IQ matched typically developing (TD) controls, made speeded discriminations between non-word pairs. Stimuli varied in PSTM load (two- or four-syllables) and speech perception load (mismatches on a word-initial or word-medial segment). Outcomes & Results: Reaction times showed effects of both non-word length and mismatch position and these factors interacted: four-syllable and word-initial mismatch stimuli resulted in the slowest decisions. Individuals with language impairment showed the same pattern of performance as those with typical development in the reaction time data. A marginal interaction between group and item length was driven by the SLI and ALI groups being less accurate with long items than short ones, a difference not found in the TD group. Conclusions & Implications: Non-word discrimination suggests that there are similarities and differences between adolescents with SLI and ALI and their TD peers. Reaction times appear to be affected by increasing PSTM and speech perception loads in a similar way. However, there was some, albeit weaker, evidence that adolescents with SLI and ALI are less accurate than TD individuals, with both showing an effect of PSTM load. This may indicate, at some level, the processing substrate supporting both PSTM and speech perception is intact in adolescents with SLI and ALI, but also in both there may be impaired access to PSTM resources.

Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment

Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI.

Development of personalised functional foods needs metabolic profiling

Purpose of review There is growing interest in applying metabolic profiling technologies to food science as this approach is now embedded into the foodomics toolbox. This review aims at exploring how metabolic profiling can be applied to the development of functional foods. Recent findings One of the biggest challenges of modern nutrition is to propose a healthy diet to populations worldwide that must suit high inter-individual variability driven by complex gene-nutrient-environment interactions. Although a number of functional foods are now proposed in support of a healthy diet, a one-size-fits-all approach to nutrition is inappropriate and new personalised functional foods are necessary. Metabolic profiling technologies can assist at various levels of the development of functional foods, from screening for food composition to identification of new biomarkers of food intake to support diet intervention and epidemiological studies. Summary Modern ‘omics’ technologies, including metabolic profiling, will support the development of new personalised functional foods of high relevance to twenty-first-century medical challenges such as controlling the worldwide spread of metabolic disorders and ensuring healthy ageing.

Interpretation and expectations among mothers of children with anxiety disorders: associations with maternal anxiety disorder

Background Models of the development and maintenance of childhood anxiety suggest an important role for parent cognitions: that is, negative expectations of children's coping abilities lead to parenting behaviors that maintain child anxiety. The primary aims of the current study were to (1) compare expectations of child vulnerability and coping among mothers of children with anxiety disorders on the basis of whether or not mothers also had a current anxiety disorder, and (2) examine the degree to which the association between maternal anxiety disorder status and child coping expectations was mediated by how mothers interpreted ambiguous material that referred to their own experience. Methods The association between interpretations of threat, negative emotion, and control was assessed using hypothetical ambiguous scenarios in a sample of 271 anxious and nonanxious mothers of 7- to 12-year-old children with an anxiety disorder. Mothers also rated their expectations when presented with real life challenge tasks. Results There was a significant association between maternal anxiety disorder status and negative expectations of child coping behaviors. Mothers’ self-referent interpretations were found to mediate this relationship. Responses to ambiguous hypothetical scenarios correlated significantly with responses to real life challenge tasks. Conclusions Treatments for childhood anxiety disorders in the context of parental anxiety disorders may benefit from the inclusion of a component to directly address parental cognitions. Some inconsistencies were found when comparing maternal expectations in response to hypothetical scenarios with real life challenges. This should be addressed in future research.

Neonatal environment exerts a sustained influence on the development of the intestinal microbiota and metabolic phenotype

The postnatal environment, including factors such as weaning and acquisition of the gut microbiota, has been causally linked to the development of later immunological diseases such as allergy and autoimmunity, and has also been associated with a predisposition to metabolic disorders. We show that the very early-life environment influences the development of both the gut microbiota and host metabolic phenotype in a porcine model of human infants. Farmpiglets were nursed by their mothers for 1 day, before removal to highly controlled, individual isolators where they received formula milk until weaning at 21 days. The experiment was repeated, to create two batches, which differed only in minor environmental fluctuations during the first day. At day 1 after birth, metabolic profiling of serum by 1H nuclear magnetic resonance spectroscopy demonstrated significant, systemic, inter-batch variation which persisted until weaning. However, the urinary metabolic profiles demonstrated that significant inter-batch effects on 3-hydroxyisovalerate, trimethylamine-N-oxide and mannitol persisted beyond weaning to at least 35 days. Batch effects were linked to significant differences in the composition of colonic microbiota at 35 days, determined by 16 S pyrosequencing. Different weaning diets modulated both the microbiota and metabolic phenotype independently of the persistent batch effects. We demonstrate that the environment during the first day of life influences development of the microbiota and metabolic phenotype and thus should be taken into account when interrogating experimental outcomes. In addition, we suggest that intervention at this early time could provide ‘metabolic rescue’ for at-risk infants who have undergone aberrant patterns of initial intestinal colonisation.