Intranasal oxytocin therapy has been used to improve various aspects of autism spectrum disorder on the basis of tenuous results from small studies. In a randomized trial involving 290 participants 3 ...to 17 years of age with autism spectrum disorder, daily use of oxytocin did not improve measures of social interaction as compared with placebo over a period of 24 weeks.
The purpose of the study was to characterize repetitive phenomena in Williams syndrome (WS). The parents of 60 subjects with WS completed the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) or ...Children’s Y-BOCS, the Yale Global Tic Severity Scale, the Stereotyped Behavior Scale, and the Spence Children’s Anxiety Scale–Parent Version. Nineteen males and 41 females participated in the study. Six subjects (10%) had obsessions only, six (10%) had compulsions only, and eleven (18%) had at least one obsession and at least one compulsion. None of the subjects had tics. Fifty subjects (83.3%) endorsed at least one stereotypy. Increased anxiety was associated with increased severity of obsessions, but not severity of compulsions or stereotypies.
Abstract A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between ...familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.
Research associating the increased prevalence of familial autoimmunity with neuropsychiatric disorders is reliant upon the ascertainment of history of autoimmune diseases from relatives. To ...characterize the accuracy of self-report, we compared self-reported diagnoses of 18 autoimmune diseases using an online self-report questionnaire to the electronic medical record (EMR) diagnoses in 1,013 adult (age 18-70 years) patients of a primary care clinic. For the 11 diseases meeting our threshold observed prevalence, we estimated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for self-reported diagnoses under the assumption that EMR-based diagnoses were accurate. Six diseases out of 11 had either sensitivity or PPV below 50%, with the lowest PPV for dermatological and endocrinological diseases. Common errors included incorrectly self-reporting type 2 diabetes mellitus (DM), when type 1 DM was indicated by the EMR, and reporting rheumatoid arthritis when osteoarthritis was indicated by the EMR. Results suggest that ascertainment of familial autoimmunity through self-report contributes to inconsistencies and inaccuracies in studies of autoimmune disease history and that future studies would benefit from incorporating EMR review and biological measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An immune-mediated subtype of autism spectrum disorder (ASD) has long been hypothesized. This article reviews evidence from family history studies of autoimmunity, immunogenetics, maternal immune ...activation, neuroinflammation, and systemic inflammation, which suggests immune dysfunction in ASD. Individuals with ASD have higher rates of co-morbid medical illness than the general population. Major medical co-morbidities associated with ASD are discussed by body system. Mechanisms by which FDA-approved and emerging treatments for ASD act upon the immune system are then reviewed. We conclude by proposing the hypothesis of an immune-mediated subtype of ASD which is characterized by systemic, multi-organ inflammation or immune dysregulation with shared mechanisms that drive both the behavioral and physical illnesses associated with ASD. Although gaps in evidence supporting this hypothesis remain, benefits of this conceptualization include framing future research questions that will help define a clinically meaningful subset of patients and focusing clinical interactions on early detection and treatment of high-risk medical illnesses as well as interfering behavioral signs and symptoms across the lifespan.
This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and ...clinically significant anxiety (Pediatric Anxiety Rating Scale PARS score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Clinical trial registration information: Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https://clinicaltrials.gov ; NCT01302964.
Parent Description of Anxiety in Angelman Syndrome Keary, Christopher J.; Mullett, Jennifer E.; Nowinski, Lisa ...
Journal of autism and developmental disorders,
08/2022, Letnik:
52, Številka:
8
Journal Article
Recenzirano
Anxiety is being increasingly identified in Angelman syndrome (AS). Qualitative questions and quantitative assessments were used to evaluate for anxiety in 50 subjects with AS. In-person evaluations ...assessed behaviors concerning for anxiety and circumstances wherein they occurred. Caregivers completed anxiety and other behavioral rating scales. Caregiver responses were categorized and compared to items from anxiety rating scales. The most common behavioral manifestation of anxiety was “aggression.” The most common circumstance was “separation from caregiver/parent.” Subjects had elevated scores on anxiety, irritability and hyperactivity scales with lower mean scores among subjects with a maternal deletion. The Pediatric Anxiety Rating Scale best captured behaviors described by caregivers. Existing anxiety scales should be adapted for use in AS.
Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD ...can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using
CPBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two
CPBR28 PET-MRI scans. Females with ASD exhibited elevated
CPBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower
CPBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable
CPBR28 SUVR across time in both groups. Elevated regional
CPBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional
CPBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.
Brief Report: Acamprosate in Fragile X Syndrome Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.
Journal of autism and developmental disorders,
11/2010, Letnik:
40, Številka:
11
Journal Article
Recenzirano
Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). We report on the first trial of acamprosate, a drug with putative mGluR5 antagonism, in three adults with ...FXS and autism. Medical records describing open-label treatment with acamprosate in 3 patients with FXS and a comorbid diagnosis of autistic disorder were reviewed. In all three patients, acamprosate was associated with improved linguistic communication. Three patients received acamprosate over a mean 21.3 weeks of treatment. All patients showed global clinical benefit as rated with the Clinical Global Impressions-Improvement scale. Marked communication improvement was unexpected and has potential implications for the treatment of FXS, as well as idiopathic autism.
Rationale
Individuals with autistic disorder (autism) frequently exhibit significant irritability marked by severe tantrums, aggression, and self-injury. Despite advances in the treatment of this ...symptom domain in autism, there remains an ongoing need for more effective and better tolerated pharmacotherapies.
Objectives
The aim of this study is to determine the effectiveness and tolerability of paliperidone for irritability in autism.
Methods
This is a prospective, 8-week open-label study of paliperidone in 25 adolescents and young adults with autism. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) Scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Concomitant medications (except antipsychotics) were permitted if dosages were stable for ≥2 months.
Results
Twenty-one (84 %) of 25 subjects ages 12–21 years (mean 15.3 years) responded to paliperidone, based on a CGI-I Scale score of 1 or 2 (very much or much improved) and ≥25 % improvement on the ABC-I. The mean final dosage of paliperidone was 7.1 mg/day (range 3–12 mg/day). Two subjects discontinued paliperidone prior to study completion (moderate sedation,
n
= 1; nonresponse,
n
= 1). Mild-to-moderate extrapyramidal symptoms were recorded in four subjects. A mean weight gain of 2.2 ± 2.6 kg (range −3.6 to +7.9 kg) was recorded. Mean age- and sex-normed body mass index increased from 23.6 to 24.2 (
p
≤ 0.001). Mean serum prolactin increased from 5.3 to 41.4 ng/mL (
p
≤ 0.0001).
Conclusions
Paliperidone treatment was associated with significant improvement in irritability and was generally well tolerated. Larger scale, placebo-controlled studies are needed to elucidate the efficacy and tolerability of paliperidone in this population.
PDF
