1. Al-Ayadhi LY, Mostafa GA. {{Low plasma progranulin levels in children with autism}}. {J Neuroinflammation}. 2011 Sep 5;8(1):111.
ABSTRACT: BACKGROUND: Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. METHODS: Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. RESULTS: Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children. On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. CONCLUSIONS: Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.
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2. Budimirovic DB, Kaufmann WE. {{What Can We Learn about Autism from Studying Fragile X Syndrome?}}. {Dev Neurosci}. 2011 Sep 1.
Despite early controversy, it is now accepted that a substantial proportion of children with fragile X syndrome (FXS) meets diagnostic criteria for autism spectrum disorder (ASD). This change has led to an increased interest in studying the association of FXS and ASD because of the clinical consequences of their co-occurrence and the implications for a better understanding of ASD in the general population. Here, we review the current knowledge on the behavioral, neurobiological (i.e., neuroimaging), and molecular features of ASD in FXS, as well as the insight into ASD gained from mouse models of FXS. This review covers critical issues such as the selectivity of ASD in disorders associated with intellectual disability, differences between autistic features and ASD diagnosis, and the relationship between ASD and anxiety in FXS patients and animal models. While solid evidence supporting ASD in FXS as a distinctive entity is emerging, neurobiological and molecular data are still scarce. Animal model studies have not been particularly revealing about ASD in FXS either. Nevertheless, recent studies provide intriguing new leads and suggest that a better understanding of the bases of ASD will require the integration of multidisciplinary data from FXS and other genetic disorders.
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3. Charles J, Harrison C, Britt H. {{Autism spectrum disorders}}. {Aust Fam Physician}. 2011 Sep;40(9):665.
In this article we use BEACH data to examine changes in the management rate of autism spectrum disorders (ASDs) from 2001 to 2011 in children aged <18 years. We also look at encounters where autism was managed during 2006-2011.
4. Cheuk DK, Wong V, Chen WX. {{Acupuncture for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev}. 2011;9:CD007849.
BACKGROUND: Autism spectrum disorders (ASD) are characterized by impairment in social interaction, impairment in communication and lack of flexibility of thought and behavior. Acupuncture, which involves the use of needles or pressure to specific points on the body, is used widely in Traditional Chinese Medicine and increasingly within a western medical paradigm. It has sometimes been used as a treatment aimed at improving ASD symptoms and outcomes, but its clinical effectiveness and safety has not been rigorously reviewed. OBJECTIVES: To determine the effectiveness of acupuncture for people with ASD in improving core autistic features, as well as communication, cognition, overall functioning and quality of life, and to establish if it has any adverse effects. SEARCH STRATEGY: We searched the following databases on 30 September 2010: CENTRAL (The Cochrane Library, 2010, Issue 3), MEDLINE (1950 to September 2010 Week 2), EMBASE (1980 to 2010 Week 38), PsycINFO, CINAHL, China Journal Full-text Database, China Master Theses Full-text Database, China Doctor Dissertation Full-text Database, China Proceedings of Conference Database, Index to Taiwan Periodical Literature System, metaRegister of Controlled Trials and the Chinese Clinical Trials Registry. We also searched AMED (26 February 2009) and Dissertation Abstracts International (3 March 2009), but these were no longer available to the authors or editorial base at the date of the most recent search. TCMLARS (Traditional Chinese Medical Literature Analysis and Retrieval System) was last searched on 3 March 2009. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials. We included studies comparing an acupuncture group with at least one control group that used no treatment, placebo or sham acupuncture treatment in people with ASD. We excluded trials that compared different forms of acupuncture or compared acupuncture with another treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed the risk of bias in the trials. We used relative risk (RR) for dichotomous data and mean difference (MD) for continuous data. MAIN RESULTS: We included 10 trials that involved 390 children with ASD. The age range was three to 18 years and the treatment duration ranged from four weeks to nine months. The studies were carried out in Hong Kong, mainland China and Egypt.Two trials compared needle acupuncture with sham acupuncture and found no difference in the primary outcome of core autistic features (RFRLRS total score: MD 0.09; 95% CI -0.03 to 0.21, P = 0.16), although results suggested needle acupuncture might be associated with improvement in some aspects of the secondary outcomes of communication and linguistic ability, cognitive function and global functioning.Six trials compared needle acupuncture plus conventional treatment with conventional treatment alone. The trials used different primary outcome measures and most could not demonstrate effectiveness of acupuncture in improving core autistic features in general, though one trial reported patients in the acupuncture group were more likely to have improvement on the Autism Behavior Checklist (RR 1.53; 95% CI 1.09 to 2.16, P = 0.02) and had slightly better post-treatment total scores (MD -5.53; 95% CI -10.76 to -0.31, P = 0.04). There was no evidence that acupuncture was effective for the secondary outcome of communication and linguistic ability, though there seemed to be some benefit for the secondary outcomes of cognitive function and global functioning.Two trials compared acupressure plus conventional treatment with conventional treatment alone and did not report on the primary outcome. Individual study results suggested there may be some benefit from acupressure for certain aspects of the secondary outcomes of communication and linguistic ability, cognitive function and global functioning.Four trials reported some adverse effects, though there was little quantitative information, and at times both intervention and control groups experienced them. Adverse effects noted included bleeding, crying due to fear or pain, irritability, sleep disturbance and increased hyperactivity. None of the trials reported on quality of life.There are a number of problems with the evidence base: the trials were few in number and included only children; six of the trials were at high risk of bias; they were heterogeneous in terms of participants and intervention; they were of short duration and follow-up; they reported inconsistent and imprecise results, and, due to carrying out large numbers of analyses, they were at risk of false positivity. AUTHORS’ CONCLUSIONS: Current evidence does not support the use of acupuncture for treatment of ASD. There is no conclusive evidence that acupuncture is effective for treatment of ASD in children and no RCTs have been carried out with adults. Further high quality trials of larger size and longer follow-up are needed.
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5. Davidovic L, Navratil V, Bonaccorso CM, Catania MV, Bardoni B, Dumas ME. {{A metabolomic and systems biology perspective on the brain of the Fragile X syndrome mouse model}}. {Genome Res}. 2011 Sep 7.
Fragile X syndrome (FXS) is the first cause of inherited intellectual disability, due to the silencing of the X-linked Fragile X Mental Retardation 1 gene encoding the RNA-binding protein FMRP. While extensive studies have focused on the cellular and molecular basis of FXS, neither human fragile X patients nor the mouse model of FXS -the Fmr1-null mouse- have been profiled systematically at the metabolic and neurochemical level to provide a complementary perspective on the current, yet scattered, knowledge of FXS. Using proton high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR)-based metabolic profiling, we have identified a metabolic signature and biomarkers associated with FXS in various brain regions of Fmr1-deficient mice. Our study highlights for the first time that Fmr1 gene inactivation has profound, albeit coordinated consequences in brain metabolism leading to alterations in: i) neurotransmitter levels, ii) osmoregulation, iii) energy metabolism and iv) oxidative stress response. To functionally connect Fmr1-deficiency to its metabolic biomarkers, we derived a functional interaction network based on the existing knowledge (literature and databases) and show that the FXS metabolic response is initiated by distinct mRNA targets and proteins interacting with FMRP, and then relayed by numerous regulatory proteins. This novel « integrated metabolome and interactome mapping » (iMIM) approach advantageously unifies novel metabolic findings with previously unrelated knowledge and highlights the contribution of novel cellular pathways to the pathophysiology of FXS. These metabolomic and integrative systems biology strategies will contribute to develop potential drug targets and novel therapeutic interventions, which will eventually benefit FXS patients.
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6. Kaufman DR, Cronin P, Rozenblit L, Voccola D, Horton A, Shine A, et al. {{Facilitating the iterative design of informatics tools to advance the science of autism}}. {Stud Health Technol Inform}. 2011;169:955-9.
This paper describes a usability evaluation study of an innovative first generation system (Data Dig) designed to retrieve phenotypic data from the large SFARI data set of 2700 families each of which has one child affected with autism spectrum disorder. The usability methods included a cognitive walkthrough and usability testing. Although the subjects were able to learn to use the system, more than 50 usability problems of varying severity were noted. The problems with the greatest frequency resulted from users being unable to understand meanings of variables, filter categories correctly, use the Boolean filter, and correctly interpret the feedback provided by the system. Subjects had difficulty forming a mental model of the organizational system underlying the database. This precluded them from making informed navigation choices while formulating queries. Clinical research informatics is a new and immensely promising discipline. However in its nascent stage, it lacks a stable interaction paradigm to support a range of users on pertinent tasks. This presents great opportunity for researchers to further this science by harnessing the powers of user-centered iterative design.
7. Olmos-Serrano JL, Corbin JG. {{Amygdala Regulation of Fear and Emotionality in Fragile X Syndrome}}. {Dev Neurosci}. 2011 Sep 1.
Fear is a universal response to a threat to one’s body or social status. Disruption in the detection and response of the brain’s fear system is commonly observed in a variety of neurodevelopmental disorders, including fragile X syndrome (FXS), a brain disorder characterized by variable cognitive impairment and behavioral disturbances such as social avoidance and anxiety. The amygdala is highly involved in mediating fear processing, and increasing evidence supports the idea that inhibitory circuits play a key role in regulating the flow of information associated with fear conditioning in the amygdala. Here, we review the known and potential importance of amygdala fear circuits in FXS, and how developmental studies are critical to understand the formation and function of neuronal circuits that modulate amygdala-based behaviors.
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8. Reddy A, Graves C, Augustyn M. {{Parents Seek Early Intervention Services for a Two-Year-Old Without Autism}}. {J Dev Behav Pediatr}. 2011 Sep 7.
CASE:: Sam is a 27-month-old boy who you have followed since birth. He lives with his parents in a small resort town approximately 90 miles outside a major city. Both his parents are professionals in their late 30s and have been highly involved in his care since birth. At the 12-month visit, they were concerned about his difficulty regulating. He was not sleeping through the night and had significant difficulty with baths. His physical examination and growth were normal. His eye contact was good, although it was difficult to see him smile. He had 1 or 2 words and was beginning to walk independently.At the 15-month checkup, they continued to be concerned about his poor regulation. He napped sporadically, and he was very difficult to take out on errands as he did not like his car seat. He now had approximately 10 single words, was using his fingers to point and very clearly waved « bye bye » as soon as you entered the room.At the 18-month checkup, they state that he has not yet learned the word « no. » He will follow a 1-step command when he wants to but now has 15 single words without any combinations. He points for his needs and to show them something. He has become increasingly « shy » around strangers and prefers to play with one other child as opposed to a larger group. He does not like loud noises and prefers to go barefoot constantly. His physical examination was again normal as was his growth. He is referred for a full hearing evaluation, which is also normal. The family was referred to early intervention, and he began receiving speech and language therapy and occupational therapy for his sensory challenges as well as a play group.At the 24-month checkup, his language continued to consist of single words-now approximately 30. When the parents do not understand what he wants, he will often tantrum and has started banging his head on the floor when frustrated. He has no repetitive behaviors and is starting to demonstrate imaginative play. Bath time has becoming increasingly challenging because he does not like the sensation of soap and the water temperature must be « just right. » You refer the child to a Developmental and Behavioral Pediatrician for evaluation and at 28 months he is seen. During his testing visit, he had decreased eye contact and followed his own agenda but improved significantly as testing progressed. As he got more comfortable, he began making good eye contact, social referenced, and exhibited joint attention with his parents and the examiner. He did not meet criteria for an autism spectrum disorder or specifically pervasive developmental disorder-not otherwise specified (PDD-NOS). He was given a diagnosis of mixed receptive and expressive language delay and disruptive behavior disorder with sensory processing problems.The parents come to you a month after their evaluation visit asking you to give him a « listed diagnosis of PDD-NOS » that could be removed when he turns 3 years so that he may qualify for increased hours of services-up to 15 hours per week-as well as applied behavioral analysis therapy. A behavioral therapist through early intervention has told the family that he would benefit from this increased intervention, specifically applied behavioral analysis but the only way he can receive it is with a « medical diagnosis » on the autism spectrum. What do you do next?
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9. Snow J, Ingeholm JE, Levy IF, Caravella RA, Case LK, Wallace GL, et al. {{Impaired Visual Scanning and Memory for Faces in High-Functioning Autism Spectrum Disorders: It’s Not Just the Eyes}}. {J Int Neuropsychol Soc}. 2011 Sep 6:1-9.
Prior studies suggest that autism spectrum disorders (ASD) are associated with a domain-specific memory impairment for faces. The underlying cause of this problem and its relation to impaired visual scanning of faces-particularly of the eyes-remains to be determined. We recorded eye movements while 22 high-functioning ASD and 21 typically developing (TD) adolescents encoded and later recognized faces and objects from a single, nonsocial object category (electric fans). Relative to TD subjects, ASD individuals had poorer memory for faces, but not fans. Correlational analyses showed significant relationships between recognition memory and fixations. Eye tracking during encoding revealed that TD subjects made more fixations to faces than fans, whereas ASD individuals did not differ in number of fixations made to each stimulus type. Moreover, although both the TD and ASD groups showed a strong preference for fixating the eyes more than the mouth, the ASD subjects were less likely than TD subjects to scan regions of the face outside of the primary facial features (i.e., eyes, nose, and mouth). We concluded that ASD individuals have a domain-specific memory impairment for faces relative to mechanical objects and that this impairment may be related to abnormal scanning during encoding. (JINS, 2011, 17, 1-9).
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10. Tonge B, Brereton A. {{Autism spectrum disorders}}. {Aust Fam Physician}. 2011 Sep;40(9):672-7.
Background Autism spectrum disorders (ASDs) are serious neurodevelopmental disorders affecting approximately one in 160 Australians. Symptoms are apparent during the second year of life causing impairments in social interaction, communication and behaviour with restricted and stereotyped interests. Objective To increase the general practitioner’s awareness of the presenting symptoms of ASDs and their associated problems in children, screening for ASDs, and the assessment process, treatment options and outcomes. Discussion This article discusses the five red flags that are autism alerts in young children. These red flags can enable GPs to play a key surveillance role in determining which young children might require further screening and referral for an ASD assessment. Because ASDs are lifelong, neurodevelopmental disorders and symptoms change over time. Therefore the GP has an ongoing role to support, educate and advise parents, other carers and the individual with an ASD. Treatment and pharmacological interventions are also discussed.
11. Tranfaglia MR. {{The Psychiatric Presentation of Fragile X: Evolution of the Diagnosis and Treatment of the Psychiatric Comorbidities of Fragile X Syndrome}}. {Dev Neurosci}. 2011 Sep 2.
Fragile X syndrome (FXS) is the leading inherited cause of mental retardation and autism spectrum disorders worldwide. It presents with a distinct behavioral phenotype which overlaps significantly with that of autism. Unlike autism and most common psychiatric disorders, the neurobiology of fragile X is relatively well understood. Lack of the fragile X mental retardation protein causes dysregulation of synaptically driven protein synthesis, which in turn causes global disruption of synaptic plasticity. Thus, FXS can be considered a disorder of synaptic plasticity, and a developmental disorder in the purest sense: mutation of the FMR1 (fragile X mental retardation 1) gene results in abnormal synaptic development in response to experience. Accumulation of this abnormal synaptic development, over time, leads to a characteristic and surprisingly consistent behavioral phenotype of attention deficit, hyperactivity, impulsivity, multiple anxiety symptoms, repetitive/perseverative/stereotypic behaviors, unstable affect, aggression, and self-injurious behavior. Many features of the behavioral and psychiatric phenotype of FXS follow a developmental course, waxing and waning over the life span. In most cases, symptoms present as a mixed clinical picture, not fitting established diagnostic categories. There have been many clinical trials in fragile X subjects, but no placebo-controlled trials of adequate size or methodology utilizing the most commonly prescribed psychiatric medications. However, large and well-designed trials of investigational agents which target the underlying pathology of FXS have recently been completed or are under way. While the literature offers little guidance to the clinician treating patients with FXS today, potentially disease-modifying treatments may be available in the near future.
