EURASIAN JOURNAL OF MEDICAL AND
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IF = 7.921
Volume 5 Issue 7, July 2025 ISSN 2181-287X
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CHILDHOOD AUTISM: CURRENT INSIGHTS INTO
PATHOGENESIS AND NEUROLOGICAL COMORBIDITY
Kodirova Nafisa Nizomiddin kizi
Student of Tashkent Pediatric Medical Institute,
faculty of II-pediatrics and medical biology, group № 531-2 pediatrics
https://doi.org/10.5281/zenodo.16255668
ARTICLE INFO
ABSTRACT
Received: 16
th
July 2025
Accepted: 20
th
July 2025
Online: 21
st
July 2025
Autism spectrum disorders (ASD) are complex
neurodevelopmental
conditions
with
increasing
prevalence worldwide. This review aims to summarize the
latest data on the multifactorial pathogenesis of ASD,
with emphasis on genetic, neuroimmune, and
environmental influences. Additionally, the article
explores the wide spectrum of neurological comorbidities
often observed in children with ASD, such as epilepsy,
sensory processing disorders, motor dysfunction, and
sleep disturbances. Modern trends in therapeutic
strategies and the importance of early, multidisciplinary
intervention are also discussed. The review highlights the
need for continued research into biomarkers and
personalized approaches to autism treatment.
KEYWORDS
Autism spectrum disorder, ASD,
pathogenesis, genetic factors,
neurodevelopment,
neuroinflammation,
neurological
comorbidity,
epilepsy, sensory processing
disorder, sleep disturbances,
gut-brain
axis,
early
intervention,
pediatric
neurology,
neuroimaging,
immune dysfunction.
ДЕТСКИЙ АУТИЗМ: СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О ПАТОГЕНЕЗЕ И
НЕВРОЛОГИЧЕСКОЙ КОМОРБИДНОСТИ
Кодирова Нафиса Низомиддин кизи
Студентка Ташкентского Педиатрического Медицинского Института, факультет II-
педиатрии и медицинской биологии, группа № 531-2 педиатрия
https://doi.org/10.5281/zenodo.16255668
ARTICLE INFO
ABSTRACT
Received: 16
th
July 2025
Accepted: 20
th
July 2025
Online: 21
st
July 2025
Расстройства аутистического спектра (РАС)
представляют собой сложные нейроразвивающиеся
состояния с растущей распространённостью во
всём мире. В обзоре представлены современные
данные о многофакторной патогенезе РАС с
акцентом на генетические, нейроиммунные и
экологические
влияния.
Дополнительно
рассматриваются
распространённые
неврологические
коморбидности,
такие
как
эпилепсия, сенсорные нарушения, моторные и
речевые отклонения, а также расстройства сна.
Освещаются современные терапевтические подходы
и
значение
раннего
мультидисциплинарного
вмешательства. Подчёркивается необходимость
KEYWORDS
РАС, аутизм, патогенез,
генетические
факторы,
нейроразвитие,
нейровоспаление,
неврологические
коморбидности, эпилепсия,
сенсорные
нарушения,
расстройства
сна,
ось
кишечник-мозг,
раннее
вмешательство,
детская
неврология,
EURASIAN JOURNAL OF MEDICAL AND
NATURAL SCIENCES
Innovative Academy Research Support Center
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Volume 5 Issue 7, July 2025 ISSN 2181-287X
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нейровизуализация,
иммунная дисфункция.
дальнейших
исследований
биомаркеров
и
персонализированных методов лечения аутизма.
BOLALARDA AUTIZM: PATOLOGENEZ VA NEVROLOGIK KOMORBIDLIK
BO‘YICHA ZAMONAVIY YONDASHUVLAR
Kodirova Nafisa Nizomiddin qizi
Toshkent Pediatriya Tibbiyot Instituti talabasi, II-pediatriya va tibbiy biologiya fakulteti,
531-2 pediatriya guruhi
https://doi.org/10.5281/zenodo.16255668
ARTICLE INFO
ABSTRACT
Received: 16
th
July 2025
Accepted: 20
th
July 2025
Online: 21
st
July 2025
Autizm spektridagi buzilishlar (ASB) butun dunyoda keng
tarqalib
borayotgan
murakkab
nevro-rivojlanish
holatlaridir. Ushbu sharhda ASBning ko‘p omilli
patogeneziga oid so‘nggi ilmiy ma’lumotlar, xususan
genetik, neyroimmun va ekologik omillarning roli
yoritiladi. Shuningdek, maqolada bolalarda uchraydigan
nevrologik komorbidliklar, jumladan epilepsiya, sezgi
buzilishlari, harakat muammolari va uyqudagi buzilishlar
muhokama
qilinadi.
Terapiyadagi
zamonaviy
yondashuvlar va erta, ko‘p sohalik aralashuvning
ahamiyati ta’kidlanadi. Tadqiqotlar davomida autizmning
biomarkerlari
va
individuallashtirilgan
davolash
strategiyalarini rivojlantirish zarurligi ko‘rsatib o‘tiladi.
KEYWORDS
ASB,
patogenez,
genetik
omillar,
neyro-rivojlanish,
neyroinflammatsiya,
nevrologik
komorbidlik,
epilepsiya, sezgi muammolari,
uyqu buzilishi, ichak-miya o‘qi,
erta
aralashuv,
bolalar
nevrologiyasi, neyrotasvirlash,
immun tizim disfunktsiyasi.
Introduction
Autism spectrum disorders (ASD) represent a significant clinical and public health
concern, especially in pediatric neurology and psychiatry. The increasing awareness and
diagnostic capabilities have led to a rise in identified cases worldwide. As reported by the
Centers for Disease Control and Prevention (CDC) in 2023, the estimated prevalence of ASD in
the United States reached 1 in 36 children aged 8 years, a notable increase compared to
previous years [1].
ASD is characterized by impairments in social communication, restricted interests, and
stereotyped behaviors, with a wide range of symptom severity. The clinical heterogeneity of
ASD often coexists with other neurodevelopmental and neurological disorders, complicating
diagnosis and management. Understanding the multifactorial etiology and comorbidities
associated with ASD is crucial for developing effective interventions and support systems.
Pathogenesis: Genetic, Neurobiological, and Environmental Mechanisms
ASD is widely recognized as a genetically influenced neurodevelopmental condition.
Genome-wide association studies (GWAS) and whole-exome sequencing have identified
numerous gene variants associated with ASD. Among them,
CHD8
,
SCN2A
,
SHANK3
,
NRXN1
,
and
SYNGAP1
are consistently linked to synaptic transmission, neuronal excitability, and
chromatin remodeling [2,3]. These genes are critical for brain development and plasticity, and
mutations can result in altered synaptogenesis and connectivity.
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Epigenetic regulation also plays a vital role in ASD pathogenesis. DNA methylation and
histone modification patterns have been found to differ in children with ASD, suggesting that
environmental factors may alter gene expression without changing the DNA sequence. For
example, maternal stress, infection, or toxic exposures during pregnancy can affect fetal gene
expression profiles and increase autism risk.
Neuroimaging findings support atypical brain development in ASD. Studies using
magnetic resonance imaging (MRI) show that early brain overgrowth is often followed by a
deceleration in growth, especially in the frontal and temporal cortices. Abnormalities in
cortical thickness, white matter integrity, and connectivity between regions such as the
default mode network
(DMN),
salience network
, and
social brain areas
are widely
documented [4].
Furthermore,
immune dysregulation
has been increasingly implicated in ASD. Children
with ASD often show elevated levels of
pro-inflammatory cytokines
(e.g., IL-6, TNF-α),
abnormal
T-cell profiles
, and
microglial activation
, suggesting ongoing neuroinflammation
[5]. Maternal immune activation (MIA) during pregnancy—such as infection or autoimmune
disorders—has been shown to increase ASD risk in offspring, possibly through disruption of
fetal brain development.
Gastrointestinal (GI) dysfunction
is another aspect frequently reported in ASD.
Altered gut microbiota composition, often termed "dysbiosis", may affect brain function
through the
gut-brain axis
. Short-chain fatty acids (SCFAs), microbial metabolites, and
immune interactions in the gut may influence neurodevelopment via systemic inflammation
and neurotransmitter regulation [6].
Environmental risk factors, while less significant than genetic ones, can act as triggers in
genetically predisposed individuals. These include
prenatal exposure to valproic acid
,
air
pollutants
,
heavy metals (e.g., lead, mercury)
, and
perinatal hypoxia
. Cumulative
exposure to multiple minor stressors may converge on common neurodevelopmental
pathways, leading to clinical manifestations of autism.
Neurological Comorbidity: Scope and Implications
Comorbid neurological conditions are reported in up to 70–80% of individuals with
ASD. Among the most prevalent are:
Epilepsy
: Occurs in 20–30% of children with ASD, particularly in those with co-
occurring intellectual disability. Seizure onset often follows a bimodal distribution—infancy
or adolescence—and may require long-term antiepileptic therapy [7].
Sleep disturbances
: Affects up to 80% of ASD patients, significantly impacting behavior
and cognitive function. Melatonin secretion abnormalities and circadian rhythm gene
mutations (e.g.,
CLOCK
,
BMAL1
) have been implicated.
Motor abnormalities
: Including
hypotonia
,
dyspraxia
,
clumsiness
, and delayed
gross/fine motor milestones, which may result from cerebellar dysfunction. Structural MRI
frequently reveals cerebellar hypoplasia, especially of the vermis [8].
Sensory processing disorders (SPD)
: Children may exhibit hyperreactivity (e.g., sound
sensitivity), hyporeactivity, or sensory seeking behaviors. SPD can manifest as distress in
crowded environments, refusal to wear certain clothes, or fascination with spinning objects.
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Cognitive impairments and developmental delays
: Nearly half of children with ASD
have below-average intellectual functioning. Executive dysfunction, impaired theory of mind,
and weak central coherence are cognitive hallmarks.
Attention-deficit/hyperactivity disorder (ADHD)
symptoms**: Present in over 50%
of children with ASD, complicating behavioral regulation and learning. Differentiation
between ASD and ADHD is important for treatment selection.
The recognition of comorbidities is essential not only for symptomatic management but
also for prognostic evaluation. For example, the presence of epilepsy and severe intellectual
disability is often associated with poorer long-term outcomes.
Therapeutic Approaches and Future Perspectives
The treatment of ASD is individualized and must address both core symptoms and
associated comorbidities.
Early intensive behavioral intervention (EIBI)
, particularly
programs based on
Applied Behavior Analysis (ABA)
, has been shown to improve social,
communication, and adaptive functioning.
Pharmacotherapy
is generally used for managing comorbid symptoms. Antipsychotics
such as
risperidone
and
aripiprazole
are FDA-approved for treating irritability and
aggression. Melatonin is often prescribed for sleep disorders, and antiepileptic drugs for
seizure control.
Emerging strategies include:
Neurofeedback therapy
and
transcranial magnetic stimulation (TMS)
, targeting
abnormal brain networks.
Probiotic supplementation
and
fecal microbiota transplantation (FMT)
for
modulating gut-brain interactions.
Oxytocin-based therapies
, aimed at enhancing social cognition.
Research into
biomarkers
(e.g., microRNAs, neuroinflammatory markers, metabolomics
profiles) holds promise for early diagnosis and subtyping.
In the long term, integration of
genetic data
,
neuroimaging
, and
behavioral
assessments
may enable precision medicine approaches in ASD.
Conclusion
Autism spectrum disorder is a multifaceted neurodevelopmental condition with a
complex interplay of genetic, neurobiological, immune, and environmental factors. The high
rate of neurological comorbidities underscores the need for comprehensive and
multidisciplinary evaluation. Advancements in genomics, neuroimaging, and systems biology
are gradually paving the way toward precision diagnostics and individualized therapies.
Continued investment in early screening, family-centered care, and translational research is
essential to improve quality of life and long-term outcomes for individuals with ASD and their
families.
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1.
Baio J. et al. Prevalence of Autism Spectrum Disorder among Children Aged 8 Years —
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IF = 7.921
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