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  • A Narrative Review on Irritability and Its Impact on Functional Impairment in Children and Adolescents with Autism Spectrum Disorder

  • Photo Drishya L* 2 Photo Arya Mohan 1 Photo Shaiju Dharan 3

  • 1Student, Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram
    2Assistant Professor, Department of Pharmacy Practice Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram
    3Principal/HOD, Department of Pharmacy Practice Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram.

Abstract

Irritability is a prevalent and challenging symptom in children and adolescents with autism spectrum disorder (ASD), often manifesting as temper outbursts, aggression, and low frustration tolerance. While core features of ASD include social communication deficits and restricted, repetitive behaviours, comorbid irritability can significantly exacerbate functional difficulties in daily life. Recent studies have highlighted that irritability is not only distressing for the individual but also contributes to increased caregiver stress and impedes therapeutic engagement. Importantly, it often overlaps with symptoms of anxiety, ADHD, and mood disorders, making it a complex and multifactorial issue. This symptomatology may also be a reaction to sensory sensitivities, communication barriers, or environmental stressors commonly experienced by individuals with ASD. The impact of irritability on functional impairment is multifaceted, affecting academic performance, peer relationships, family dynamics, and adaptive skills. Children and adolescents with higher irritability levels are more likely to face school exclusion, social isolation, and difficulty with self-care and community functioning. Furthermore, persistent irritability may hinder the effectiveness of behavioural and educational interventions, thereby limiting developmental progress. Interventions that target irritability, including parent training programs, behavioural therapy, and pharmacological options like atypical antipsychotics, have shown promise in improving both behaviour and overall functioning. However, more research is needed to tailor these approaches based on individual profiles and to explore the neurobiological underpinnings of irritability in ASD. Recognizing and addressing irritability as a core treatment target is essential for enhancing the quality of life and long-term outcomes for youth with autism.

Keywords

Autism, Irritability, Hyperactivity, antipsychotics.

Introduction

Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental disorder marked by ongoing difficulties with social communication and interaction, along with restricted and repetitive patterns of behavior or interests, which can differ widely in their intensity and form. Individuals with ASD may also exhibit differences in sensory processing, learning styles, and emotional regulation.

Globally, autism affects approximately one out of every 100 children, according to estimates from the World Health Organization. According to the Centers for Disease Control (CDC), roughly 1 out of every 59 children in the U.S about 1.68% are diagnosed with autism spectrum disorder (ASD) by the age of 8 [1]. In India, it is estimated that around 18 million people are living with autism. Approximately one out of every 68 children are identified as having autism spectrum disorder. The boys are more frequently affected with autism with a ratio of about 1: 3 as compared to girls.

The condition typically emerges in early childhood and can impact various aspects of daily functioning, including relationships, education, and adaptive skills. Although the precise cause of autism spectrum disorder (ASD) remains unclear, the researches suggests that it may occur as a results from a combination of genetic influences and environmental factors. Recent research has shed light on both genetic and environmental factors that may play a role in autism development, including specific gene variations like DDX53 and prenatal exposure to air pollutants such as nitric oxide. Furthermore, imbalances in the gut microbiome have been linked to changes in brain activity that affect how autistic children process emotions and sensory information. Irritability in children with autism spectrum disorder (ASD) has long been a focus of clinical research, with studies exploring both pharmacological and behavioral treatments. [2]

Autism Spectrum Disorder (ASD) can significantly affect various aspects of a child's daily life. Children with autism often struggle with communication, both verbal and non-verbal, which can make social interactions challenging. They may have difficulty in understanding social cues and expressing their emotions, leading to isolation or misunderstandings with peers and family members. Repetitive behaviour and a need for strict routines can make it hard for them to adapt to changes in their environment. Sensory sensitivities, like increased sensitivity to noises, textures, or bright lights, can lead to significant discomfort and distress in daily life. These challenges can impact their ability to engage in school activities, form relationships, or manage daily tasks like self-care or following through with instructions [3,4].

While each child experiences autism differently, these factors can affect their overall independence and quality of life. The way individuals with autism engage in daily activities can vary widely based on factors such as their age, level of support required, cognitive abilities, sensory preferences, and any additional health conditions they may have.

ROLE OF IRRITABILITY IN FUNCTIONAL IMPAIRMENT

Irritability is a frequently observed symptom in children and adolescents with autism spectrum disorder (ASD), often manifesting as temper outbursts, aggression, or low frustration tolerance. While not a core diagnostic feature, it significantly contributes to the emotional and behavioral challenges faced by individuals with ASD [5].

This heightened irritability can interfere with daily functioning, strain social relationships, and increase caregiver stress, making it a critical focus in both clinical assessment and intervention planning. To tailor treatment appropriately, clinicians must first identify children who exhibit high levels of irritability [6,7]. This can be achieved by counting the irritable symptoms reported by caregivers using widely recognized and accessible diagnostic tools, such as the Diagnostic Interview of Children and Adolescents [8]. Recognizing the role of irritability in functional impairment among children with autism is crucial for effective support and intervention. Recent psychometric evaluations suggest that the items on the ABC-I scale capture a broader spectrum of irritability-related behaviours, including self-harm, rather than focusing primarily on mood-related symptoms like anger. [9,10]

Irritability can hinder a child's participation in social, academic, and everyday activities, frequently resulting in more behavioral challenges and a decline in their ability to function independently. It may also hinder progress in therapy and learning environments, making it harder for children to reach their full potential. Understanding this connection allows for more personalized approaches that address both emotional regulation and functional skills, ultimately improving the child’s quality of life and easing the challenges faced by families and caregivers [11]. In 2002, the NIMH's RUPP Autism Network found that risperidone was effective in lessening severe behavioral issues such as aggression, self-injury, and tantrums in a study involving 101 children diagnosed with autism. [12,13] A reduced connection between the amygdala and the ventrolateral prefrontal cortex during tasks involving fear could be a key factor in distinguishing children with autism spectrum disorder (ASD) who display disruptive behaviors from those who do not [14].

UNDERLYING CAUSES OF IRRITABILITY IN CHILDREN WITH AUTISM

Irritability in children with autism spectrum disorder (ASD) can arise from a combination of neurobiological, cognitive, and environmental factors. Here’s a breakdown of the key mechanisms:

NEUROBIOLOGICAL MECHANISMS:

  1. Brain Structure and Function:
  • Amygdala hyperactivity: The amygdala is a critical brain region responsible for detecting and processing emotional stimuli, especially those related to fear and threat. In children with autism, an overactive or dysregulated amygdala may cause them to perceive everyday situations as more stressful or threatening than they actually are. This heightened emotional sensitivity can lead to exaggerated responses, such as irritability, frustration, or sudden anger, even in relatively minor or routine situations. [15,16]
  • Prefrontal cortex dysfunction: Dysfunction in brain regions such as the ventrolateral prefrontal cortex (vlPFC), which is crucial for emotional regulation, can impair a child's capacity to manage their impulses and control emotional outbursts. When this area doesn't function optimally, the child may struggle to pause and reflect before reacting, leading to increased irritability and difficulty coping with stress or frustration [17]. This lack of regulation may make even minor challenges feel overwhelming, triggering strong behavioural responses.
  1. Neurotransmitter Imbalance:
  • Serotonin: Low serotonin levels are associated with increased aggression and irritability.
  • Dopamine: Dysregulation in dopamine pathways can affect mood regulation and behavioural control.
  • GABA/glutamate imbalance: These neurotransmitters influence excitability in the brain; an imbalance may lead to heightened arousal and poor impulse control [18].

COGNITIVE AND SENSORY FACTORS:

  1. Sensory Processing Difficulties:
    • Children with ASD often experience sensory overload (e.g, loud noises, bright lights), which can trigger irritability when they are unable to cope.
  2. Difficulty with Communication:
    • Limited verbal and non-verbal communication can lead to frustration when the child cannot express needs, wants, or discomfort manifesting as irritability. [19,20]
  3. Rigidity and Intolerance to Change:
    • Many children with ASD have a strong preference for routine. Unexpected changes can lead to anxiety and irritability due to poor cognitive flexibility. [21,22,23] The cognitive behavioural therapy is efficacious and can be considered for children’s with autism.[10]

PREVALENCE AND MANIFESTATION OF IRRITABILITY IN CHILDREN AND ADOLESCENT WITH ASD

Irritability is commonly reported among children and adolescents with autism spectrum disorder (ASD), with studies indicating that a significant proportion experience frequent temper outbursts, mood swings, and episodes of aggression or self-injury.[24]

While exact prevalence rates vary, research suggests that over half of individuals with ASD exhibit moderate to severe irritability at some point. This symptom often appears as an exaggerated response to frustration, changes in routine, or sensory overload, and can be influenced by communication difficulties or unmet needs. Its presence not only complicates the core challenges of ASD but also contributes to increased emotional and behavioural difficulties in daily life.[25,26]

TOOLS/SCALES USED TO MEASURE IRRITABILITY

Several standardized tools are used to assess irritability in children and adolescents with autism spectrum disorder (ASD), helping clinicians and researchers quantify the severity and frequency of these behaviour.[27,28] One of the most widely used instruments is the Aberrant Behaviour Checklist (ABC), particularly its Irritability subscale, which evaluates symptoms such as aggression, tantrums, mood changes, and self-injurious behaviour. Caregiver responses to each item on the ABC-I subscale are theoretically considered to reflect a single underlying factor that represents irritability in youth with ASD. [29,30]

Other tools include the Child Behaviour Checklist (CBCL), which measures a range of emotional and behavioural problems, including irritability-related items, and the Emotion Dysregulation Inventory (EDI), designed to capture emotional reactivity and regulation difficulties in neurodevelopmental conditions.[31,32] These tools are valuable for both diagnostic clarification and monitoring treatment outcomes.

  1. Functional Impairment in Autism Spectrum Disorder (ASD)

Autism Spectrum Disorder (ASD) is a condition that impacts how a person interacts with others, communicates, and behaves. However, beyond these core features, individuals with ASD often face significant challenges in everyday functioning.[33] These are referred to as functional impairments, which can affect their independence, education, employment, and social relationships.

  • Social Functioning: People with ASD often find it difficult to understand social cues,    maintain conversations, or develop meaningful relationships. This can lead to isolation, misunderstanding, and difficulty participating in group settings such as school or work.[34,35]
  • Communication Challenges: Functional impairments also include trouble with both verbal and non-verbal communication. Some individuals may speak very little or not at all, while others may struggle with the subtleties of language, such as sarcasm or tone of voice.[36].
  • Executive Functioning Deficits: Executive functioning refers to a set of cognitive skills, such as working memory, adaptability, and self-regulation, that are essential for managing daily tasks and behaviour. Individuals with ASD may find it hard to plan, organize, or shift between tasks. These challenges can make academic or work-related responsibilities particularly difficult. [37,38]
  • Adaptive Skills: Adaptive functioning refers to the ability to carry out daily life activities, like dressing, cooking, managing money, or using public transport. Many individuals with ASD may have delays in these areas, requiring support even in adulthood.
  • Emotional and Behavioural Regulation: ASD can also affect how a person manages emotions and responds to stress. Unexpected changes in routine or overwhelming sensory experiences can trigger anxiety, cause outbursts, or lead to social withdrawal [39,40].

 Functional impairment in ASD is diverse and varies from person to person. These challenges often continue across the lifespan, affecting independence and quality of life. Early intervention, skill-building programs, and supportive environments can help individuals with ASD improve their functional abilities and lead more independent, fulfilling lives.[35,40]

Functional impairment refers to the reduction or inability to perform typical or expected tasks in various areas of life due to physical, psychological, or emotional challenges. These impairments can affect multiple domains, including:

  • Social Impairment: Difficulty in forming or maintaining relationships, engaging in social activities, or communicating effectively with others. This can manifest as withdrawal from friends or family, trouble with social cues, or feeling disconnected in social situations.[50,47]
  • Academic Impairment: Struggles with learning, concentration, completing assignments, or attending school regularly[45]. This may result in poor academic performance, failure to meet developmental milestones, or challenges in acquiring new knowledge and skills.
  • Family Life Impairment: Disruptions in fulfilling family roles or responsibilities. This can include issues with communication, conflict, caregiving responsibilities, or difficulty contributing to family dynamics due to mental or physical health issues.[41,42]
  • Occupational Impairment: Difficulty performing at work, which may include poor job performance, absenteeism, or challenges in fulfilling job duties. This can stem from mental health problems, physical health conditions, or lack of necessary skills.

The severity and scope of the impairment can differ significantly from person to person, depending on factors such as the type of condition, its duration, and the level of support available. For example, a person with a mild anxiety disorder may experience occasional difficulty in social situations, whereas someone with severe schizophrenia may struggle with maintaining employment, forming relationships, or even managing daily hygiene. Functional impairment not only affects the individual's quality of life but may also place a burden on caregivers, families, and support systems.[44]

Functional impairment in autism is multidimensional rooted in motor control, sensory processing, brain-network disruptions, inflammatory/gut mechanisms, and often compounded by under-recognized medical/mental comorbidities. The latest evidence supports holistic, transdisciplinary assessments and supports as essential for improving real-life functioning and quality of life in autistic individuals.

Functional Domains affected by irritability in Children and Adolescents with Autism Spectrum Disorder (ASD)

Table 1 : Domains affected by irritability in autism spectrum disorder

DOMAIN AFFECTED

MANIFESTATION OF IRRITABILITY

FUNCTIONAL IMPAIRMENT OBSERVED

SUPPORTING EVIDENCE

Emotional Regulation

Frequent temper outbursts, low frustration tolerance

Difficulty adapting to changes; mood dysregulation

Linked to amygdala hyperactivity and poor coping strategies

Social Functioning

Aggression toward peers, poor social reciprocity

Social withdrawal, peer rejection

Limits formation of relationships and social learning

Academic Performance

Inattention, refusal to comply, disruptive classroom behaviour

Decreased academic achievement; increased disciplinary actions

Teachers may report learning disruptions
 

COMMON DOMAINS AFFECTED IN ASD CHILDREN

In children with autism spectrum disorder (ASD), several key domains of functioning can be affected, though the severity and impact vary significantly from one child to another. Some of the most common domains affected in children with ASD include:

1. Social Communication and Interaction

Children with Autism Spectrum Disorder (ASD) often exhibit significant challenges in social communication and interaction. They may struggle with social reciprocity, making it difficult to engage in typical back-and-forth conversations, interpret social cues, or express interest in others’ emotions or viewpoints.[46] Nonverbal communication can be challenging, making it harder for children to understand or use gestures, facial expressions, eye contact, and body language. As a result, many children may struggle to initiate social interactions and may seem distant or unresponsive to others, including peers, adults, and family members.

2. Repetitive Behaviour’s and Restricted Interests

A characteristic feautre of autism is the presence of repetitive behaviour and restricted interests in activities. Children may engage in stereotyped movements or speech, such as hand-flapping, rocking, or echolalia (repeating words or phrases). They often exhibit a strong preference for routine, displaying distress when familiar patterns are disrupted. Additionally, they may have intense, narrowly focused interests in specific topics, objects, or activities, which can dominate their attention and limit engagement in other experiences.[48,38]

3. Sensory Processing Difficulties

Sensory processing issues are common in children with ASD and can significantly affect their daily functioning. The children’s display heightened sensitivity, responding intensely to sensory inputs such as bright lights, loud sounds, or specific textures. Others may show hypo responsiveness, seeming indifferent to sensory input. Sensory-seeking behaviours, such as repetitive touching, spinning, or seeking specific tactile sensations, are also frequent and may serve as coping mechanisms or forms of stimulation.

4. Cognitive and Learning Differences

Cognitive profiles in children with ASD vary widely. Some may have intellectual disabilities, while others demonstrate average or above-average intelligence, often excelling in areas like mathematics, music, or visual-spatial tasks [49,16]. Despite these strengths, many children face challenges with abstract thinking and flexible problem-solving, which can impact their ability to grasp complex concepts or adapt to new situations.

5. Emotional Regulation

Children with ASD struggle a lot to control and manage their emotions . They may find it equally challenging to interpret others emotional states. This can lead to increased frustration and anxiety, often resulting in behavioural outbursts or meltdowns, particularly in response to stress, unexpected changes, or sensory overload [50,52].

6. Adaptive Functioning (Life Skills)

Children with ASD often face difficulties in adaptive functioning, which includes daily living skills necessary for independence. They require support and training to do their daily activities such as dressing, eating, toileting, and for maintaining personal hygiene[51,54]. As they grow older, they may also need assistance with functioning in school or workplace settings, highlighting the need for life skills interventions tailored to their individual capacities.

7. Motor Skills

Motor development can be delayed in children with ASD. Fine motor skills, such as handwriting or using utensils, and gross motor skills, like running or playing sports, may be affected. Motor stereotypies repetitive movements such as hand-flapping or spinning are also common and may serve as self-soothing behaviour’s or responses to over stimulation. [53,39]

8. Language and Speech Development Some children’s experience significant speech delays, others may develop language with unusual characteristics. These can include overly formal speech, repetitive phrases, or monotone intonation. Pragmatic language skills using language appropriately in social contexts are frequently impaired, making it difficult for children to engage in effective and meaningful communication.

CONCLUSION

Irritability is a common and often distressing feature associated with autism spectrum disorder (ASD), significantly impacting the daily lives of individuals and their families. It can present through aggression, tantrums, or emotional outbursts and is often linked to underlying challenges such as communication difficulties, sensory sensitivities, anxiety, and difficulty with emotional regulation. Understanding the root causes of irritability in children with ASD is crucial for developing effective support strategies [55]. A combination of behavioural interventions, tailored therapies, and, when appropriate, pharmacological treatments can help reduce irritability and improve overall quality of life. Continued research is essential to better understand the complex nature of irritability in ASD and to create more personalized, compassionate, and evidence-based approaches to care. The irritability can directly impair a child's ability to function in key areas of their life, including social relationships, academic performance, family dynamics, and self-regulation. This can lead to a cascade of challenges in other domains, worsening the child’s overall quality of life. Early intervention to address irritability and its underlying causes is crucial to reduce functional impairments and improve outcomes for children dealing with this issue.

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Photo
Drishya L
Corresponding author

Assistant Professor, Department of pharmacy practice, Ezhuthachan College Of Pharmaceutical Sciences, Marayamuttom, Neyyattinkara.

Photo
Arya Mohan
Co-author

Student, Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram

Photo
Shaiju Dharan
Co-author

Principal/HOD, Department of Pharmacy Practice Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram.

Arya Mohan, Drishya L.*, Shaiju Dharan, A Narrative Review on Irritability and Its Impact on Functional Impairment in Children and Adolescents with Autism Spectrum Disorder, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 3061-3071. https://doi.org/10.5281/zenodo.15715841

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