165 research outputs found
A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders: Study Protocol for AIMS-2-TRIALS-CT1
No full textAutism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles
Land lease agreement between Dominguez Estate Company and G. Edwin and Gertrude L. Murphy, February 19, 1945
No full textAgreement for 5.7 acres of the G.M. Dominguez allotment for the term March 1, 1945 to February 28, 1946 with a yearly rent of $142.50
Autism in adults. New biological findings and their translational implications to the cost of clinical services
No full textThere is increasing evidence that children with autism spectrum disorder (ASD) have differences in brain growth trajectory. However, the neurobiological basis of ASD in adults is poorly understood. We report evidence that brain anatomy and aging in people with ASD is significantly different as compared to controls—so that in adulthood they no longer have a significantly larger overall brain volume, but they do have anatomical and functional abnormalities in frontal lobe, basal ganglia and the limbic system. Further we present preliminary evidence that females have significantly greater abnormalities in brain than males to express the same symptom severity of ASD (i.e. the female brain is “protective” against developing ASD). Also we present preliminary evidence that, in adults, clinical services for autism in the United Kingdom are experiencing very significantly increased demand; but that just over 50% of people seeking a diagnosis from one expert service do not have ASD. This consumes very significant health care resources, and so we need to identify new cost-effective methods to aid current diagnostic practice. We present initial evidence offering proof of concept that brain anatomy can be used to accurately distinguish adults with autism from healthy controls, and from some other neurodevelopmental disorders (ADHD). Hence further studies are required to determine if sMRI can become an aid to current diagnostic practice in young adults with ASD. Lastly we report evidence that differences in serotonin, glutamate and GABA may partially explain neuroanatomical and neurofunctional abnormalities in people with ASD, and that genetic influences on brain maturation vary across the lifespan (with 5-HT transporter polymorphisms having significant modulatory effects in children but not adults)
Autism is associated with interindividual variations of gray and white matter morphology
No full textBackground: Although many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group. Methods: We studied 183 individuals with autism and 157 nonautistic individuals (age range, 6–30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions—A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants’ GM volume and WM diffusion tensor images, and group comparisons of modality shared variances were examined. Subsequently, we performed univariate and multivariate brain-behavior correlation analyses to separately explore the relationships between brain patterns and clinical profiles. Results: One multimodal pattern was significantly related to autism. This pattern was primarily associated with GM volume in bilateral insula and frontal, precentral and postcentral, cingulate, and caudate areas and co-occurred with altered WM features in the superior longitudinal fasciculus. The brain-behavior correlation analyses showed a significant multivariate association primarily between brain patterns that involved variation of WM and symptoms of restricted and repetitive behavior in the autism group. Conclusions: Our findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism and show that the complex clinical autism phenotype can be interpreted by brain covariation patterns that are spread across the brain involving both cortical and subcortical areas
The effect of intranasal oxytocin on neural response to facial emotions in healthy adults as measured by functional MRI: A systematic review
No full textAbnormalities in responses to human facial emotions are associated with a range of psychiatric disorders. Addressing these abnormalities may therefore have significant clinical applications. Previous meta-analyses have demonstrated effects of the neuropeptide oxytocin on behavioural response to facial emotions, and effects on brain, as measured by functional MRI. Evidence suggests that these effects may be mediated by sex and the role of eye gaze. However, the specific effect of oxytocin on brain response to facial emotions in healthy adults has not been systematically analysed. To address this question, this further systematic review was conducted. Twenty-two studies met our inclusion criteria. In men, oxytocin consistently attenuated brain activity in response to negative emotional faces, particularly fear, compared with placebo, while in women, oxytocin enhanced activity. Brain regions consistently involved included the amygdala, fusiform gyrus and anterior cingulate cortex. In some studies, oxytocin increased fixation changes towards the eyes with enhanced amygdala and/or fusiform gyrus activation. By enhancing understanding of emotion processing in healthy subjects, these pharmacoimaging studies provide a theoretical basis for studying deficits in clinical populations. However, progress to date has been limited by low statistical power, methodological heterogeneity, and a lack of multimodal studies
Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder
No full textIntroduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence. Methods: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland–Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis. Results: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [−8.1%, 16.74%]; no subgroup differences χ2 = 1.24, p-value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [−0.87, 1.04]; χ2 = 0.02, p-value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used. Discussion: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed
Anatomy of the dorsal default-mode network in conduct disorder: Association with callous-unemotional traits
No full textWe recently reported that emotional detachment in adult psychopathy was associated with structural abnormalities in the dorsal 'default-mode' network (DMN). However, it is unclear whether these differences are present in young people at risk of psychopathy. The most widely recognised group at risk for psychopathy are children/adolescents with conduct disorder (CD) and callous-unemotional (CU) traits. We therefore examined the microstructure of the dorsal DMN in 27 CD youths (14-with/13-without CU traits) compared to 16 typically developing controls using DTI tractography. Both CD groups had significantly (p < 0.025) reduced dorsal DMN radial diffusivity compared to controls. In those with diagnostically significant CU traits, exploratory analyses (uncorrected for multiple comparisons) suggested that radial diffusivity was negatively correlated with CU severity (Left: rho = -0.68, p = 0.015). These results suggest that CD youths have microstructural abnormalities in the same network as adults with psychopathy. Further, the association with childhood/adolescent measures of emotional detachment (CU traits) resembles the relationship between emotional detachment and network microstructure in adult psychopaths. However, these changes appear to occur in opposite directions - with increased myelination in adolescent CD but reduced integrity in adult psychopathy. Collectively, these findings suggest that developmental abnormalities in dorsal DMN may play a role in the emergence of psychopathy
Fronto-striatal circuitry and inhibitory control in autism: Findings from diffusion tensor imaging tractography
No full textIntroduction
Repetitive behaviour and inhibitory control deficits are core features of autism; and it has been suggested that they result from differences in the anatomy of striatum; and/or the ‘connectivity’ of subcortical regions to frontal cortex. There are few studies, however, that have measured the micro-structural organisation of white matter tracts connecting striatum and frontal cortex.
Aims
To investigate differences in bulk volume of striatum and micro-structural organisation of fronto-striatal white matter in people with autism; and their association with repetitive behaviour and inhibitory control.
Methods
We compared the bulk volume of striatum (caudate nucleus, putamen and nucleus accumbens) and white matter organisation of fronto-striatal tracts using (respectively) structural magnetic resonance imaging (sMRI) and tract specific diffusion tensor imaging (DTI) measures in 21 adults with autism and 22 controls. We also assessed performance on a cognitive inhibition (go/nogo) task.
Results
Bulk volume of striatal structures did not differ between groups. However, adults with autism had a significantly smaller total brain white matter volume, lower fractional anisotropy of white matter tracts connecting putamen to frontal cortical areas, higher mean diffusivity of white matter tracts connecting accumbens to frontal cortex and worse performance on the go/nogo task. Also, performance on the go/nogo task was significantly related to anatomical variation when both groups were combined; but not within the autism group alone.
Conclusions
These data suggest that autism may be associated with differences in the anatomy of fronto-striatal white matter tracts
Selective Amygdala Hypoactivity to Fear in Boys With Persistent Conduct Problems After Parent Training
No full textBACKGROUND: Parenting interventions reduce antisocial behavior (ASB) in some children with conduct problems (CPs), but not others. Understanding the neural basis for this disparity is important because persistent ASB is associated with lifelong morbidity and places a huge burden on our health and criminal justice systems. One of the most highly replicated neural correlates of ASB is amygdala hypoactivity to another person's fear. We aimed to assess whether amygdala hypoactivity to fear in children with CPs is remediated following reduction in ASB after successful treatment and/or if it is a marker for persistent ASB. METHODS: We conducted a prospective, case-control study of boys with CPs and typically developing (TD) boys. Both groups (ages 5-10 years) completed 2 magnetic resonance imaging sessions (18 ± 5.8 weeks apart) with ASB assessed at each visit. Participants included boys with CPs following referral to a parenting intervention group and TD boys recruited from the same schools and geographical regions. Final functional magnetic resonance imaging data were available for 36 TD boys and 57 boys with CPs. Boys with CPs were divided into those whose ASB improved (n = 27) or persisted (n = 30) following the intervention. Functional magnetic resonance imaging data assessing fear reactivity were then analyzed using a longitudinal group (TD/improving CPs/persistent CPs) × time point (pre/post) design. RESULTS: Amygdala hypoactivity to fear was observed only in boys with CPs who had persistent ASB and was absent in those whose ASB improved following intervention. CONCLUSIONS: Our findings suggest that amygdala hypoactivity to fear is a marker for ASB that is resistant to change following a parenting intervention and a putative target for future treatments
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