A report on rosuvastatin’s role in alleviating behavioral problems in autism spectrum disorder with a SYNaptic GTPase-Activating Protein 1 mutation

Disrupting the balance between excitatory and inhibitory neurotransmission in the developing brain has been causally linked with intellectual disability (ID) and autism spectrum disorders (ASD). Excitatory synapse strength is regulated in the central nervous system by controlling the number of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). De novo genetic mutations of the synaptic GTPase-activating protein (SynGAP) are associated with ID and ASD. SynGAP is enriched at excitatory synapses and genetic suppression of SynGAP increases excitatory synaptic strength. However, exactly how SynGAP acts to maintain synaptic AMPAR content is unclear. We show here that SynGAP limits excitatory synaptic strength, in part, by suppressing protein synthesis in cortical neurons. The data presented here from in vitro, rat and mouse cortical networks, demonstrate that regulation of translation by SynGAP involves ERK, mTOR, and the small GTP-binding protein Rheb. Furthermore, these data show that GluN2B-containing NMDARs and the cognitive kinase CaMKII act upstream of SynGAP and that this signaling cascade is required for proper translation-dependent homeostatic synaptic plasticity of excitatory synapses in developing cortical networks.

We studied the correlation between the caregiver's feelings of burden and the cognitive, behavioral and functional impairment of demented patients. We attempted to show the influence of caregiver's feelings of burden on their perception of the patients' functional status and to establish the predictors of feelings of burden. Twenty-five probable Alzheimer disease patients (NINCDS-ADRDA criteria) were assessed on cognitive measures and functional status (DAFS). The caregiver's index of burden (CIB), obtained from an adapted version of the Zarit Burden Interview, was correlated with the caregiver's report on the patient's instrumental activities of daily living (IADL) and physical self-maintenance functions (ADL); total and partial DAFS scores, and patient's cognitive and behavioral problems rated with the Functional Dementia Scale (FDS). The CIB correlated with the caregiver's report on the patient's behavioral disturbances (r = 0.71, p < 0.001) and physical self-maintenance activities (r = 0.62, p < 0.001), but not with cognitive impairment, IADL and the DAFS. The patients showed better functional performance in the direct assessment than in that reported by their caregivers (mainly in shopping, feeding, dressing, and ambulation). Thus, burden may foster a growing intolerance of the caregiver, inducing an underestimation of the patient's actual functional competence. The caregiver's report on the patient's behavioral problems was the best predictor of feelings of burden (P = 19,9, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: In recent decades, a steady increase in the prevalence of autism spectrum disorders around the world has been reported. It is known that autism spectrum disorders requires early diagnosis and medical intervention. By identifying the risks of autism spectrum disorders, doctors can help the child and family get qualified help as soon as possible. Given the variety of functional disorders in autism spectrum disorders, these patients require special rehabilitation programs and therefore physicians planning work in the field of physical therapy and medical rehabilitation should be oriented in this problem.&#x0D; AIMS: To determine the level of awareness of the problem of autism spectrum disorders among doctors of different specialties planning to work in the field of physical and rehabilitation medicine.&#x0D; MATERIAL AND METHODS: A survey was conducted on the KCAHW questionnaire of 105 doctors of 8 medical specialties who underwent primary retraining in the cycle "Physical and Rehabilitation Medicine" at the Department of Physical Therapy, Sports Medicine and Medical Rehabilitation of the Russian Medical Academy of Continuous Professional Education.&#x0D; RESULTS: According to the results of filling out the KCAHW questionnaire, the median of correct answers was 14 [7; 19] out of 19 possible, which is the average value of the level of knowledge about autism spectrum disorders. Our research shows that there is a lack of knowledge in the relationship between autism and epilepsy and mental retardation, as well as the relationship between the disease and poor nutrition. Among the respondents, there was also a misunderstanding about the age of the child at which the first signs of autism spectrum disorders can be suspected: 60 (57.1%) of the survey participants correctly determined that autism begins in childhood, 35 (33.3%) of the surveyed doctors believed that autism occurs in infancy, and 10 (9.5%) people indicated the neonatal period.&#x0D; CONCLUSION: The KCAHW questionnaire is a reliable tool for assessing health care providers' knowledge of childhood autism. The conducted research allows us to conclude that doctors are not sufficiently knowledgeable in the field of knowledge about autism spectrum disorders. The totality of all the respondents' answers indicates the importance of additional information about modern research on the problem of autism spectrum disorders for all doctors planning further work in the field of physical and rehabilitation medicine.

Behaviour and emotional problems are highly prevalent in children with autism spectrum disorder (ASD). In typically developing children, attachment quality acts as a risk/protective factor for behavioural outcomes and adjustment, warranting investigation in children with ASD. We investigated the relationship between attachment and child behaviour and emotional problems in children with ASD and comorbid intellectual disability. Data were collected from parent-child dyads where children were diagnosed with ASD and ID (n=28) or other developmental disabilities (n=20). Children with ASD had higher levels of behaviour and emotional problems and more attachment difficulties than children with other developmental disabilities. Poorer attachment quality contributed uniquely to the variance in child behaviour and emotional problems. Interventions targeting behaviour and emotional problems in children with ASD may benefit from an attachment model which addresses the child's difficulty in using caregivers as a coregulatory agent of emotions.

The aim of current study was to examine the nature and prevalence of feeding problems and mealtime behavior problems in children with ASD comparing to children with other neurodevelopmental disorders (NNDs) and TD children. We also investigated the impact of intelligence quotient (IQ) and/or emotional and behavioral problems on feeding and mealtime behavior problems. Participants completed the following tests: Social Communication Questionnaire (SCQ), Child Behavior Checklist (CBCL), Brief Autism Mealtime Behavior Inventory (BAMBI) and Behavioral Pediatric Feeding Assessment Scale (BPFAS). Children with ASD showed more feeding and mealtime behavior problems including food refusal (p<.001, p<.001) and limited variety of foods (p=.014; p=.018) compared with NDDs and TD children. ASD group showed more problems in mealtime behavior (p=.034) and parent behaviors (p=.028) compared to TD group. Internalizing (p=.003) and externalizing (p=.008) problems were positively related to parent frustration during mealtime in ASD group. These results suggest that routine screening for feeding and mealtime behavior problems among children with ASD is necessary to prevent dietary inadequacies that may be associated with eating habits.

There is growing interest in the development of behavioral parent interventions targeting emotional and behavioral problems in children with autism spectrum disorders. Such interventions have potential to improve a number of child and parental well-being outcomes beyond disruptive child behavior. This systematic review and meta-analysis assesses evidence for the efficacy of behavioral parent interventions for disruptive and hyperactive child behavior in autism spectrum disorders, as well as parenting efficacy and stress. A total of 11 articles from nine randomized controlled trials were included. Sufficient data were available to calculate standardized mean difference and show favorable effects of behavioral parent interventions on parent-reported measures of child disruptive behavior (standardized mean difference = 0.67), hyperactivity (standardized mean difference = 0.31) and parent stress (standardized mean difference = 0.37); effects on parent efficacy are less clear (standardized mean difference = 0.39, p = 0.17). There were insufficient data to explore intervention effects on internalizing behavior in autism spectrum disorders, parenting behaviors, or observational and teacher-reported outcomes, providing important avenues for future research. This review adds to growing evidence of the efficacy of behavioral parent interventions for child behavior and parental well-being in autism spectrum disorders (Prospero: CRD42016033979).

Effectively serving students with autism spectrum disorders (ASDs) requires professionals to possess specialized knowledge, skills, and understanding. When students with ASDs are from culturally or linguistically diverse (CLD) families, the professionals assessing and providing services to the students need the additional dimension of how cultural and linguistic differences may affect identification, assessment, and treatment strategies.

“A developmental disability that hinders the normal functioning of the brain, affecting, in varying degrees, communication skills and social interaction. Repetitive behaviours, and different ways of learning, paying attention, or reacting to things are often distinctive signs”. This standard definition of autism fails to describe the complexity of a condition that ranges in its manifestations from severe intellectual impairment to superior cognitive skills, like in the Asperger syndrome. To comprise such diversity, autism disorders are now covered under the umbrella term “autism spectrum disorder” (ASD). In most cases, ASD manifests during the first 5 years of life, with boys significantly more likely to be diagnosed than girls. ASD usually goes together with several other problems that frequently include anxiety, sleep disorders, or epilepsy. No cure exists; treatment, such as speech therapy, just attempts to alleviate specific deficits of autistic patients. > Nothing is simple in autism. Even the real number of people affected is uncertain. Nothing is simple in autism. Even the real number of people affected is uncertain. The US CDC estimates that about 1 in 68 (or 1.5%) of children in the USA are living with ASD (http://www.cdc.gov/ncbddd/autism/data.html). The WHO has a more conservative estimate, last revised in January this year, of 1 in 160 children, based on a larger set of epidemiological surveys (http://www.who.int/mediacentre/factsheets/autism-spectrum-disorders/en/). Needless to say, most studies were conducted in developed countries, and the prevalence of ASD in many low‐ and middle‐income countries remains largely unknown. > Along the years, many potential causes have been indicated, including genetic and environmental factors, exposure to toxins during pregnancy, wide gaps between parent ages, and so on Although the general consensus is that prevalence rates are increasing globally, this point is debated too. Some analyses indicate that a large percentage of the increase in ASD owes to improved awareness and …

Background. The level of awareness of future doctors is an important factor that can further affect the quality of life of children with autism spectrum disorders. The problem has both scientific significance due to the lack of such studies in domestic science, and practical significance for identifying problem areas in the system of pediatric education. Aim. To identify the level of awareness of pediatric faculties students about autism spectrum disorders, methods for their diagnosis and treatment, technologies for non-medical intervention. Material and methods. A questionnaire, aimed at identifying the awareness of medical students about autism, methods of its diagnosis, patient routing and self-assessment of knowledge, was developed. The questionnaire included 29 questions, which could be conditionally divided into blocks: questions on knowledge about autism, action scenarios and routing, self-assessment of awareness of autism spectrum disorders, assessment of environmental components for children with such disorders, passport. Data collection was carried out using Google forms. The survey involved 408 students of pediatric faculties of 7 Russian medical universities of Kazan, Yaroslavl, Nizhny Novgorod, Krasnoyarsk, Irkutsk, Izhevsk, Kirov. The survey was conducted in December 2020. The type of research can be defined as a questionnaire survey, which was carried out in two stages (field and analytical) from December 2020 to March 2021. The survey was conducted among 14th year (144 people), 5th year (116 people) and 6th year students (125 people). The selection of subgroups was due to the specifics of the educational process: until the second semester of the 4th year, pediatric students do not study disciplines related to the problem of autism spectrum disorders, 5th year students study neurology and psychiatry, 6th year students additionally have experience in outpatient practice. The obtained data were processed using the SPSS package. Results. Officially accepted in Russia at the time of the survey, the medical interpretation of autism spectrum disorders as a group of complex disintegrative disorders of mental development was indicated by only a third (32.8%) of the medical students surveyed. Another part of the respondents (28.7%) considered autism to be a genetic disorder in the development of the nervous system due to the lack of inhibition of certain genes. The high proportion of students (21.1%) who define autism as mental retardation associated with socio-pedagogical neglect, causes concern. Senior students were more likely to give more relevant answers about the factors of autism spectrum disorders (2=22.318 at p=0.034). Only 14.2% of students were able to indicate the age of the child for screening the risk of such disorders, 19.1% correctly named the scale used for screening. 71.3% of students did not know about non-medical interventions for autism spectrum disorders, more than 90% did not have information about institutions that families with a child with autism can apply for professional help. Conclusion. Insufficient awareness of students of pediatric faculties on the problems of autism spectrum disorders, issues of screening, interventions and routing of children with autism was revealed.

As the genetics of intellectual disability (ID) and autism spectrum disorders (ASDs) are unraveled, a key issue is whether genetically divergent forms of these disorders converge on common biochemical/cellular pathways and hence may be amenable to common therapeutic interventions. This study compares the pathophysiology associated with the loss of fragile X mental retardation protein (FMRP) and haploinsufficiency of synaptic GTPase-activating protein (SynGAP), two prevalent monogenic forms of ID. We show that Syngap(+/-) mice phenocopy Fmr1(-/y) mice in the alterations in mGluR-dependent long-term depression, basal protein synthesis, and dendritic spine morphology. Deficits in basal protein synthesis can be rescued by pharmacological interventions that reduce the mGlu5 receptor-ERK1/2 signaling pathway, which also rescues the same deficit in Fmr1(-/y) mice. Our findings support the hypothesis that phenotypes associated with genetically diverse forms of ID/ASDs result from alterations in common cellular/biochemical pathways.

The aim of current study was to examine the nature and prevalence of feeding problems and mealtime behavior problems in children with autism spectrum disorder (ASD) comparing to children with other neurodevelopmental disorders (NNDs) and TD children. We also investigated the impact of intelligence quotient (IQ) and/or emotional and behavioral problems on feeding and mealtime behavior problems. Participants completed the following tests: Social Communication Questionnaire (SCQ), Child Behavior Checklist (CBCL), Brief Autism Mealtime Behavior Inventory (BAMBI) and Behavioral Pediatric Feeding Assessment Scale (BPFAS). Children with ASD showed more feeding and mealtime behavior problems including food refusal (P<0.001, P<0.001) and limited variety of foods (P=0.014; P=0.018) compared with NDDs and TD children. ASD group showed more problems in mealtime behavior (P=0.034) and parent behaviors (P=0.028) compared to TD group. Internalizing (P=0.003) and externalizing (P=0.008) problems were positively related to parent frustration during mealtime in ASD group. These results suggest that routine screening for feeding and mealtime behavior problems among children with ASD is necessary to prevent dietary inadequacies that may be associated with eating habits.

Neurological complications and behavioral problems in patients with phenylketonuria in a Follow-up Unit

The aim of this review is to evaluate the studies on changes in the enteric nervous system in autism spectrum disorder and to present current developments. Autism spectrum disorder is a combination of neurodegenerative disorders characterised by genetically and environmentally variable restricted social communication with impaired repetitive behaviours that negatively affect social communication. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), autism spectrum disorder is subdivided into autistic disorder, Asperger’s disorder, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. It has been reported that certain brain areas in the cerebellum, limbic system and cortex are affected in neuropathology of autism spectrum disorder. The enteric nervous system is a major component of the gutbrain axis. The enteric nervous system is composed of a network of neurons and glial cells responsible for coordinating many aspects of gastrointestinal function. The enteric nervous system is responsible for the control and coordination of local motility in the gastrointestinal tract, the movement of fluids through the mucosal epithelium, changes in blood flow and immune system interactions. Impaired communication between the gut and brain resulting in incompatibility of the gut-brain axis in people with autism spectrum disorder. Digestive problems and gastrointestinal dysfunction occur depending on these. By means of bidirectional communication on the intestine-brain axis, problems occurred in both systems may have negative effects on the systems in mutual way. People with autism spectrum disorder also have gastrointestinal problems because of changes in the enteric nervous system. More studies on the relationship between autism spectrum disorder and enteric nervous system are needed to solve these problems. As a result of these studies, improvement of gastrointestinal problems in autism spectrum disorder will improve the overall quality of life in people with autism spectrum disorder. Keywords: Autism spectrum disorder, enteric nervous system, gastrointestinal symptom

BACKGROUND: The problem of medical rehabilitation of patients with autism spectrum disorders (ASD) is extremely urgent. The prevalence of ASD among the world's population is about 1%. It is known that children with ASD are difficult to respond to psychological and speech therapy correction and drug treatment. Today, one of the pressing issues is the choice of non-drug methods of treatment. Given the variety of functional disorders in ASD, these patients require special rehabilitation programs and therefore physicians planning work in the field of physical therapy and medical rehabilitation should be oriented in this problem.&#x0D; AIMS: Of the study was to study the relevance of the ASD problem for the clinical activities of doctors of various specialties planning to work in the field of physical and rehabilitation medicine, their level of qualifications, activity and motivation in providing medical care to patients with ASD.&#x0D; MATERIAL AND METHODS: A survey was conducted on the author's questionnaire of 116 doctors of 8 medical specialties who underwent primary retraining in the cycle "Physical and Rehabilitation Medicine" at the Department of Physical Therapy, Sports Medicine and Medical Rehabilitation of the RMANPO of the Ministry of Health of Russia.&#x0D; RESULTS: The study showed that pediatricians and neurologists are significantly more likely to meet patients with ASD in their practice than doctors of other specialties (p 0.05). An analysis of the answers of all respondents indicates the importance of additional informing doctors about modern research on the problem of ASD. When asked "What sources of information about medical support for children with autism spectrum disorders would you definitely use" 81 (69.8%) respondents indicated seminars and conferences, 50 (43.1%) Russian magazines, books, textbooks, 46 (39.7%) special sites and materials of social networks, 30 (25.9%) advanced training programs in the system of continuing professional education, the rest of the doctors preferred modern foreign literature and the experience of colleagues. Absolutely all respondents indicated the need for medical rehabilitation for children with ASD, however, 28 (24.1%) respondents believe that it is necessary to consider each case of the disease individually. The majority of the respondents indicated the expediency of sanatorium-resort treatment for patients with ASD. Doctors were also asked about the need to use basic ICF kits in the rehabilitation of patients with autism: 64 (55.2%) respondents answered positively, 44 (37.9%) found it difficult to answer and 8 (6.9%) gave a negative answer. In matters of non-drug treatment of patients with ASD, the leading positions are taken by: art therapy, hydrotherapy, music therapy, physiotherapy exercises and animal therapy. However, methods with proven effectiveness in this category of patients, such as transcranial forms of brain stimulation and biofeedback, were chosen by only 65.5% of respondents. Only 34.5% of respondents indicated the possibility of using Bobath therapy, Vojta therapy and PNF therapy in patients with ASD.&#x0D; CONCLUSION: Doctors are not sufficiently knowledgeable in the field of modern methods of physical and rehabilitation medicine that can be successfully used in children with ASD. The totality of all the respondents' answers indicates the importance of additional informing doctors about modern research on the problem of ASD, as well as the need to implement educational programs that will take into account current trends in the development of physical and rehabilitation medicine for this category of patients.

Neonatal irritable sleep-wake rhythm as a predictor of autism spectrum disorders