Clinical Research on Autism Spectrum Disorder, Treatments, Causes and Symptoms
Autism spectrum disorder (ASD) is a complex neurological and behavioral condition that affects a person’s social interaction, communication, interests and behavior. ASD includes a wide range of symptoms and severity levels, making each individual situation unique.
Pathogenesis of autism
The mechanism of autism development is currently not well understood. Its different forms have their own characteristics of pathogenesis.
In general, there are several critical periods in a child’s development during which the most intense neurophysiological changes in the brain occur: 14-15 months, 5-7 years, 10-11 years. Pathological processes that fall within critical periods lead to developmental disorders.
With endogenous (caused by internal factors) childhood autism, the development of the child’s psyche in the early stages occurs asynchronously. This manifests itself in a violation of the sequence of motor, speech, and emotional maturation. During the normal development of a child, more complex mental functions one by one replace simpler ones. In the case of autism, there is an “interlayering” of simple functions with complex ones, for example, babbling appears after one year along with simple words.
The pathogenesis of autism-like syndrome with chromosomal abnormalities, metabolic disorders, organic brain damage may be associated with damage to certain brain structures.
In some cases, the maturation and restructuring of cells in the cerebral cortex, hippocampus and basal ganglia are disrupted.
Computed tomography images of children with ASD reveal changes in the cerebellum, brain stem, frontal cortex, and expansion of the lateral ventricles.
Evidence of impaired dopamine metabolism in the brain in autism is provided by data from positron tomography studies and hypersensitivity of dopamine receptors in the brain structures of children with autism in some of its forms.
Causes of Autism Spectrum Disorders
The causes of the development of autism spectrum disorders (ASD) are still not fully understood. Since the 1970s, many theories have emerged to explain the origin of autism. Some of them, for example, the “cold mother” theory, were subsequently refuted.
In the modern view, ASD is a polyetiological disease, that is, its development is associated with a combination of various factors. The main reasons include:
Genetic factors
Recent studies in Russia and abroad are actively studying the genes responsible for the occurrence of ASD. According to recent data, about half of these genes are widely distributed in the population, but the manifestation of the disease depends on their interaction and the influence of environmental factors.
Structural and functional brain disorders
With the advent of magnetic resonance imaging (MRI), it has become possible to study the brain in detail. People with ASD show changes in the structure of various brain structures, such as the frontal lobes, cerebellum, limbic system and brainstem. Changes in brain size have also been noted in children with ASD compared to healthy children: at birth it is reduced, but then increases sharply during the first year of life. Poor blood supply to the brain and cases of epilepsy also often accompany autism.
Biochemical changes
Numerous studies have been devoted to the study of brain metabolic disorders involved in the transmission of nerve impulses. For example, a third of children with ASD have elevated levels of serotonin in the blood. Other studies have shown elevated levels of glutamate and aspartate in all children with autism. There is a hypothesis that autism is associated with impaired absorption of certain proteins, such as gluten and casein, and research in this direction continues.
Denial of the vaccination myth
The popular myth linking autism to vaccinations is untrue. A study suggesting a link between measles vaccinations and the development of autism was published in the late 1990s in the Lancet journal. However, 10 years later it turned out that the study data were falsified, and the article was retracted after legal proceedings.
As a result, modern science continues to explore the many factors that may contribute to the development of ASD, recognizing the complexity and diversity of causes of this condition.
Main characteristics of ASD
Social interaction
People with ASD often have difficulty in social interactions. This may manifest as a lack of awareness of social cues such as facial expressions, gestures and voice intonation. They may have difficulty forming and maintaining friendships, preferring to be alone, or may be uncomfortable in social situations.
Communication
Communication difficulties in ASD can range from complete lack of speech to difficulty holding a conversation. Some people may use unusual speech patterns, such as echolalia (repetition of words or phrases). Others may have a rich vocabulary but not understand how to use language correctly in social contexts.
Behavior and interests
Stereotyped or repetitive movements such as rocking or flapping of arms are common. People with ASD may have limited and intense interests that occupy a significant amount of their time and attention. They may experience significant distress when their routine or environment changes.
Causes and risk factors
The causes of ASD are not fully understood, but the condition is believed to be caused by a complex interaction of genetic and environmental factors. Research suggests that inherited genetic mutations may play a significant role in ASD. In addition, environmental factors during pregnancy and early childhood may also contribute to the development of the disorder.
Diagnosis and treatment
Diagnosis of ASD is usually made through observations of the child’s behavior and interviews with parents and teachers. There are several diagnostic tools, such as ADOS (Schedule of Autism Diagnostic Observation) and ADI-R (Revised Autism Diagnostic Interview), that help professionals make a diagnosis.
Treatment approaches
Although there are currently no known treatments that can completely cure ASD, there are many therapeutic approaches that can help improve the quality of life for people with the disorder.
Regenerative medicine as a promising direction
In recent years, regenerative medicine has become one of the most promising areas in the study and treatment of ASD. Regenerative medicine focuses on repairing or replacing damaged cells, tissues, and organs using a variety of techniques, including stem cells, biomaterials, and biologically active molecules.
Stem cells
Research has shown that stem cells have the potential to repair damaged neurons and improve neural plasticity. Stem cell therapy may improve cognitive function and reduce behavioral symptoms in people with ASD. However, this method is still in the clinical trial stage, and further research is needed to confirm its effectiveness and safety.
Biomaterials and molecules of biological activity
Another promising approach is the use of biomaterials and molecules that can stimulate tissue regeneration and improve neural connections. These techniques may help restore brain functions impaired in ASD and improve behavior and cognition.
Phase II clinical trial of the safety and effectiveness of intravenous cord blood infusion for the treatment of children with autism spectrum disorders
Researchers from Duke University in the US completed an open-label phase 1 safety and tolerability study in 25 children diagnosed with ASD who received autologous umbilical cord blood (UCB) and were followed for a year ( NCT02176317 ). UCB was administered as a single infusion without prior immunosuppression. The safety and tolerability profile of autologous UCB infusion in ASD was excellent. Improvements in social communication abilities were noted on the caregiver-administered Vineland II Adaptive Behavior Scales and the Pervasive Developmental Disorders Inventory (PDDBI). The clinician-administered Global Clinical Impression Improvement Scale reflected positive changes in core ASD symptoms during the 6-month post-infusion period in approximately 60% of participants, as reflected by improvements in social communication skills, receptive/expressive language, reductions in repetitive behaviors, and decreases in sensory sensitivity. . The same group continued a double-blind, randomized phase 2 trial (NCT02847182) to evaluate the safety and effectiveness of UCB compared to placebo in improving social communication abilities. Children included in the study received a single intravenous infusion of autologous (n=56) or allogeneic (n=63) UCB or placebo (n=61).The infusions were well tolerated and patients were assessed 6 months after the procedure. The results showed no evidence of improvement in social communication or other autism symptoms. However, in the subgroup of children without intellectual deficits, those receiving UCB showed significant improvements in communication skills, exploratory measures (attention to toys and sustained attention), and increases in alpha and beta electroencephalographic power.
