Neuropsychological outcomes of childhood acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare form of acute encephalopathy, predominantly occurring in childhood, which has a typical radiological phenotype including bilateral, symmetrical, diffusion-restricted lesions of the thalami; posterior putamen; cerebellum; and brainstem. To date, no study has systematically examined the long-term cognitive and psychological impact of ANE. The current study describes the neuropsychological outcomes of three paediatric cases of ANE, ranging from 18 months to 10 years post ANE. All three cases displayed inattention, fine motor difficulties and anxiety. Social difficulties were also reported in all cases. The severity of long-term impairment was associated with acute presentation, as well as convalescent neuroimaging. These findings highlight the need for detailed neuropsychological assessment and long-term rehabilitation.

Parenting preschoolers with autism: Socioeconomic influences on wellbeing and sense of competence.

BACKGROUND: Previous research suggests that parents raising a child with autism experience higher levels of psychological distress than parents of typically developing children and parents of children with other developmental disorders. Little is known, however, about the intersection between the effects of socioeconomic status (SES) on the wellbeing and sense of parental competency of parents of pre-schoolers with autism and how it relates to child symptom severity. AIM: To examine the relationship between their child's symptom severity, SES, as measured by neighbourhood advantage and occupational status, on the psychological wellbeing and perceived parenting competence among parents of preschoolers with autism. METHODS: Parents of 117 preschool-aged children with a diagnosis of autism spectrum disorder (ASD), 107 mothers and 54 fathers, completed questionnaires about their child's symptoms of ASD and functioning, their own perceptions of their wellbeing and parental competence on entry to an early intervention program in Sydney, Australia. Parents also provided demographic information pertaining to their occupation, level of education attained and address (postcode). All children were also assessed for their severity of symptoms using the Autism Diagnostic Observation Schedule. The Australian Socioeconomic Index of occupational status as a measure of familial SES and the Index of Relative Socio-economic Advantage and Disadvantage as a measure of neighbourhood advantage were used to examine the impact of SES on parental sense of competence and wellbeing. RESULTS: Compared to normative populations, both mothers and fathers in our sample reported significantly higher levels of parenting sense of efficacy but lower levels of interest in the parenting role. Mothers also displayed higher levels of satisfaction. Both mothers and fathers displayed higher levels of depression than normative populations with mothers also reporting greater levels of stress and anxiety. Child symptom severity was associated with maternal parenting competency with these relationships amplified among mothers with higher familial SES and who lived in areas of greater neighbourhood advantage. Increased adaptive functioning was associated with better maternal wellbeing, particularly among mothers who lived in areas of greater neighbourhood advantage. Contrastingly, paternal parenting competence was generally not influenced by child adaptive functioning or symptom severity, although for those in higher familial SES brackets, children's symptom severity and maladaptive symptoms were negatively related to paternal sense of parenting efficacy. There was a trend towards moderate relationships between lower familial SES and greater depression, stress and anxiety among fathers, but no relationship with their child's ASD symptom severity or functioning. CONCLUSION: SES differentially impacts wellbeing and sense of parenting competence and its relationship to the impact of child symptoms for mothers and fathers of preschoolers with autism.

A negative association between brainstem pontine grey-matter volume, well-being and resilience in healthy twins

Background: Associations between well-being, resilience to trauma and the volume of grey-matter regions involved in affective processing (e.g., threat/reward circuits) are largely unexplored, as are the roles of shared genetic and environmental factors derived from multivariate twin modelling. Methods: This study presents, to our knowledge, the first exploration of well-being and volumes of grey-matter regions involved in affective processing using a region-of-interest, voxel-based approach in 263 healthy adult twins (60% monozygotic pairs, 61% females, mean age 39.69 yr). To examine patterns for resilience (i.e., positive adaptation following adversity), we evaluated associations between the same brain regions and well-being in a trauma-exposed subgroup. Results: We found a correlated effect between increased well-being and reduced grey-matter volume of the pontine nuclei. This association was strongest for individuals with higher resilience to trauma. Multivariate twin modelling suggested that the common variance between the pons volume and well-being scores was due to environmental factors. Limitations: We used a cross-sectional sample; results need to be replicated longitudinally and in a larger sample. Conclusion: Associations with altered grey matter of the pontine nuclei suggest that basic sensory processes, such as arousal, startle, memory consolidation and/or emotional conditioning, may have a role in well-being and resilience.

Systemic adverse events after botulinum neurotoxin A injections in children with cerebral palsy.

AIM: To identify factors that increase the likelihood of systemic adverse events after botulinum neurotoxin A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A prospective observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Occurrences of systemic adverse events, defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death were determined at follow-up. The relationship between systemic adverse events and eight preinjection variables (age, Gross Motor Function Classification System [GMFCS] level, history of dysphagia, gastrostomy, aspiration pneumonia, recent history of illness, BoNT-A dose, and type of sedation) were examined using univariable and multivariable logistic regression with generalized estimating equations methods. RESULTS: In total 591 children underwent 2219 injection episodes with follow-up in 2158 (97%) cases. Systemic adverse events were reported in 77 (3.6%) injection episodes. Univariable analysis suggested that GMFCS levels IV and V, a history of dysphagia, gastrostomy, aspiration pneumonia, and increasing BoNT-A dose increase the likelihood of systemic adverse events. In multivariable analysis, a history of dysphagia (odds ratio [OR] 3.42) and/or aspiration pneumonia (OR 2.31) remained associated with increased likelihood of systemic adverse events. INTERPRETATION: A history of dysphagia and/or aspiration pneumonia are the factors that most increase the likelihood of systemic adverse events after BoNT-A. WHAT THIS PAPER ADDS: Systemic adverse events occur in 3.6% of botulinum neurotoxin A (BoNT-A) injection episodes. Dysphagia and/or aspiration pneumonia are associated with increased likelihood of systemic adverse events. Multivariable models showed no evidence of association between Gross Motor Function Classification System and systemic adverse events. Multivariable models showed no evidence of association between BoNT-A dose and systemic adverse events.

The Feasibility of Using the BrightHearts Biofeedback-Assisted Relaxation Application for the Management of Pediatric Procedural Pain: A Pilot Study.

OBJECTIVE: The objective of this pilot study was to assess the acceptability and feasibility of using BrightHearts, a biofeedback-assisted relaxation application (app), in children undergoing painful procedures. METHODS: Thirty children 7 to 18 years of age undergoing a medical procedure (peripheral blood collection, botulinum toxin injection, or intravenous cannula insertion) participated. Participants used BrightHearts, a heart rate-controlled biofeedback-assisted relaxation training app delivered via an iPad with heart rate measured through a pulse oximeter worn on the ear or thumb. Feasibility was assessed through observations and patient, parent/carer, and healthcare professional feedback. Patient, parent/carer, and healthcare professional satisfaction with BrightHearts was rated using investigator-developed surveys. RESULTS: Eighty-three percent of child participants reported that they found BrightHearts helpful during the procedure and that they would use BrightHearts again. All parents and 96% of healthcare professionals indicated they would use BrightHearts again. Sixty-four percent of healthcare providers perceived that BrightHearts assisted with the ease of performing the procedure. Qualitative analyses found 2 themes: (1) BrightHearts calms through providing distraction and biofeedback and (2) the impact of BrightHearts on the procedure. CONCLUSIONS: This pilot study demonstrates the feasibility of using biofeedback-assisted relaxation delivered via the BrightHearts app in children undergoing peripheral blood collection and cannulation. Future studies are required to evaluate BrightHearts' efficacy in reducing pain and anxiety during painful procedures and distinguish the effects of a biofeedback-mediated app from distraction.

Developing BrightHearts: A Pediatric Biofeedback-Mediated Relaxation App to Manage Procedural Pain and Anxiety.

OBJECTIVE: The objective of this study was to develop a child-friendly biofeedback-mediated relaxation device called BrightHearts. METHODS: Qualitative data were collected at a tertiary pediatric hospital to inform an iterative design process. Clinicians participated in expert group interviews to identify practical considerations that would facilitate the use of BrightHearts during procedures and provide feedback on prototype designs. Children 7 to 18 years of age participated in interactive exhibitions of the prototypes and were interviewed about their experiences using BrightHearts. RESULTS: Twenty-four clinicians participated in 6 group interviews. Thirty-nine children participated in interactive exhibitions, and 21 were interviewed. Clinicians placed high value on the following factors in the management of procedural pain: providing children with an element of control, the use of relaxation techniques, and the use of portable electronic devices such as iPads. They highlighted the need for BrightHearts to be cost effective, portable, and capable of engaging children's interest. They confirmed the utility of developing a biofeedback-assisted relaxation device for children. Based on the factors identified by clinicians, BrightHearts was developed as an iPad application (app) paired with a wireless heart rate monitor. The BrightHearts heart rate biofeedback app displays digital geometric artwork that responds to changes in heart rate. Children 7 to 17 years of age understood the concept of biofeedback and operated the app by slowing their heart rates. CONCLUSION: The BrightHearts app can be used to teach children biofeedback-assisted relaxation. Ongoing studies are evaluating its efficacy for the management of procedural pain in children.

Growth charts for Australian children with achondroplasia.

Achondroplasia is an autosomal dominant disorder, the most common genetic cause of short stature in humans. Reference curves for head circumference, weight, height, and BMI are needed in clinical practice but none exist for the Australian population. This study aimed to produce head circumference, height, weight, and BMI reference percentile curves for Australian children and adolescents with achondroplasia. Measurements of head circumference, height and weight taken at clinical visits were retrospectively extracted from the electronic medical record. Age was corrected for prematurity. Patients were excluded from head circumference analysis if they had significant neurosurgical complications and from the weight and BMI analysis when they had a clinical diagnosis of overweight. Measurements were available on 138 individuals (69 males and 69 females) taken between 1970 and 2015, with over 50% collected since 2005. A total of 3,352 data points were available. The LMS method was used to produce growth charts with estimated centiles (10, 25, 50, 75, and 90th) separately for males and females. For females birth weight was 3 kg (2.5-3.5 kg), birth length 48 cm (44-50 cm) and head circumference 37.5 cm (36-39 cm), adult height was 125 cm (116-132 cm), weight 42 kg (34-54 kg), and head circumference 58 cm (55.5-60.5 cm) all 50th centile (10-90th). For males birth weight was 3.5 kg (3-4 kg), length 49 cm (46-52 cm) and head circumference 38.5 cm (36-41 cm), adult height was 134 cm (125-141 cm), weight 41 kg (24.5-57 kg) and head circumference 61 cm (58-64 cm). The curves are similar to previously published reference data from the USA and have expected population wide variation from curves from an Argentinian population. Despite limitations of our curves for adolescents (12 years and older) due to data paucity, these Australian growth charts for children and adolescents with achondroplasia will be a useful reference in clinical practice.

Long-Term Neuropsychological Outcomes of Childhood Onset Acute Disseminated Encephalomyelitis (ADEM): a Meta-Analysis.

The long-term neurocognitive prognosis of childhood onset acute disseminated encephalomyelitis (ADEM) is unclear. This review and quantitative synthesis of the available literature examined whether there are long-term impacts of childhood ADEM on neurocognitive functioning. A search of online databases (MEDLINE, EMBASE, EBSCO CINAHL, PsycINFO and the Cochrane Database of Systematic Reviews) from their inception to October 2015 and reference lists identified 13 papers eligible for inclusion in the systematic review; seven of these were eligible for inclusion in meta-analyses. The systematic review indicated that, at a group level there is a positive long-term neuropsychological outcome from childhood onset ADEM. However, despite the apparent absence of long-term negative impacts of ADEM at a group level, at an individual level impairments in the areas of IQ, attention, executive functioning, processing speed, learning and memory, visuospatial skills and internalising symptoms were found in up to 43% of patients when aggregated across the studies. No significant negative effect of ADEM for any of the neuropsychological domains examined was found in meta-analyses. However, the effects for Processing Speed (r mean = -0.296 (CI 95% = -0.605-0.013)) and Internalising symptoms (r mean = 0.242 (CI 95% = -0.014-0.564)) approached significance (p = 0.06), suggesting a trend towards ADEM leading to long-term reduced processing speed and elevated internalising symptoms. Together, our findings suggest that despite a generally positive neurocognitive outcome post childhood ADEM there are a subset of individuals who can suffer from ongoing specific cognitive impairments. Clinical implications and research priorities are discussed.

The shared and unique genetic relationship between mental well-being, depression and anxiety symptoms and cognitive function in healthy twins.

Alterations to cognitive function are often reported with depression and anxiety symptoms, yet few studies have examined the same associations with mental well-being. This study examined the association between mental well-being, depression and anxiety symptoms and cognitive function in 1502 healthy adult monozygotic (MZ) and dizygotic (DZ) twins, and the shared/unique contribution of genetic (G) and environmental (E) variance. Using linear mixed models, mental well-being was positively associated (p < .01) with sustained attention (ß = 0.127), inhibition (ß = 0.096), cognitive flexibility (ß = 0.149), motor coordination (ß = 0.114) and working memory (ß = 0.156), whereas depression and anxiety symptoms were associated (p < .01) with poorer sustained attention (ß = -0.134), inhibition (ß = -0.139), cognitive flexibility (ß = -0.116) and executive function (ß = -0.139). Bivariate twin modelling showed well-being shared a small environmental correlation with motor coordination and a small genetic correlation with working memory. Trivariate twin modelling showed well-being shared a small genetic correlation with inhibition, whereas depression and anxiety symptoms shared a small environmental correlation with inhibition. The remaining variance was mostly driven by unique G and/or E variance. Overall, well-being and depression and anxiety symptoms show both independent and shared relationships with cognitive functions but this is largely attributable to unique G or E variance and small shared G/E variance between pairs of variables.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not.

Sex differences in the shared genetics of dimensions of self-reported depression and anxiety.

BACKGROUND: The prevalence of depression and anxiety symptoms and their comorbidity varies between males and females for reasons still unknown. This study aims to test whether differences between males and females in self-reported symptoms and their covariation are caused by variations in the magnitude of genetic and environmental factors. METHODS: 750 monozygotic and dizygotic healthy twin pairs (18-60 years; M=39.77 years) participated in the TWIN-E project. Univariate and multivariate genetic modelling was undertaken using the Depression Anxiety Stress Scale (DASS-42). RESULTS: Additive genetics and unique environment contributed to self-reported depression (heritability, h(2): 34%), anxiety (h(2): 30%) and stress (h(2): 34%) scores in univariate models, and to the common latent factor (h(2): 39%) in the multivariate model. No sex differences in magnitude of estimates for DASS-42 scores were found in the univariate model. However when considering correlated depression and anxiety symptomatology only shared genetic factors between depression and anxiety contributed to depression scores in males, but both specific and shared genetic factors contributed to depression scores in females. LIMITATIONS: The results are limited to the sample of healthy, community, adult, same sex twin pairs who participated in the study. CONCLUSIONS: Differences in males and females in genetic aetiology of self-reported dimensions of depression are only apparent when taking into consideration the covariation with self-reported anxiety. This difference is highlighted by the finding that both common and specific genetic factors contribute to self-reported depression in females but not males. This novel finding may help explain the increased incidence of depression symptoms in females.

Specific and common genes implicated across major mental disorders: a review of meta-analysis studies.

Major efforts have been directed at family-based association and case-control studies to identify the involvement of candidate genes in the major disorders of mental health. What remains unknown is whether candidate genes are associated with multiple disorders via pleiotropic mechanisms, and/or if other genes are specific to susceptibility for individual disorders. Here we undertook a review of genes that have been identified in prior meta-analyses examining specific genes and specific mental disorders that have core disruptions to emotional and cognitive function and contribute most to burden of illness- major depressive disorder (MDD), anxiety disorders (AD, including panic disorder and obsessive compulsive disorder), schizophrenia (SZ) and bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD). A literature review was conducted up to end-March 2013 which included a total of 1519 meta-analyses across 157 studies reporting multiple genes implicated in one or more of the five disorders studied. A total of 134 genes (206 variants) were identified as significantly associated risk variants for MDD, AD, ADHD, SZ or BD. Null genetic effects were also reported for 195 genes (426 variants). 13 genetic variants were shared in common between two or more disorders (APOE e4, ACE Ins/Del, BDNF Val66Met, COMT Val158Met, DAOA G72/G30 rs3918342, DAT1 40-bp, DRD4 48-bp, SLC6A4 5-HTTLPR, HTR1A C1019G, MTHR C677T, MTHR A1298C, SLC6A4 VNTR and TPH1 218A/C) demonstrating evidence for pleiotrophy. Another 12 meta-analyses of GWAS studies of the same disorders were identified, with no overlap in genetic variants reported. This review highlights the progress that is being made in identifying shared and unique genetic mechanisms that contribute to the risk of developing several major psychiatric disorders, and identifies further steps for progress.

The heritability of mental health and wellbeing defined using COMPAS-W, a new composite measure of wellbeing.

Mental health is not simply the absence of mental illness; rather it is a distinct entity representing wellness. Models of wellbeing have been proposed that emphasize components of subjective wellbeing, psychological wellbeing, or a combination of both. A new 26-item scale of wellbeing (COMPAS-W) was developed in a cohort of 1669 healthy adult twins (18-61 years). The scale was derived using factor analysis of multiple scales of complementary constructs and confirmed using tests of reliability and convergent validity. Bivariate genetic modeling confirmed its heritability. From an original 89 items we identified six independent subcomponents that contributed to wellbeing. The COMPAS-W scale and its subcomponents showed construct validity against psychological and physical health behaviors, high internal consistency (average r=0.71, Wellbeing r=0.84), and 12-month test-retest reliability (average r=0.62, Wellbeing r=0.82). There was a moderate contribution of genetics to total Wellbeing (heritability h(2)=48%) and its subcomponents: Composure (h(2)=24%), Own-worth (h(2)=42%), Mastery (h(2)=40%), Positivity (h(2)=42%), Achievement (h(2)=32%) and Satisfaction (h(2)=43%). Multivariate genetic modeling indicated genetic variance was correlated across the scales, suggesting common genetic factors contributed to Wellbeing and its subcomponents. The COMPAS-W scale provides a validated indicator of wellbeing and offers a new tool to quantify mental health.