Autistic Spectrum Disorder

Autism spectrum disorder is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction along with restricted, repetitive patterns of behavior, interests, or activities.

2. Epidemiology

Comorbidity in ASD is the rule, not the exception ^[2]:

Comorbidity	Approximate Prevalence	Notes
Non-ASD developmental disorder	~83%	Especially language disorders (expressive and receptive)
Intellectual disability (ID)	~31% meet criteria for ID; ~23% borderline	Previously thought ~70% had ID; revised downward with broader ASD definition
Genetic/chromosomal disorders	~10%	Fragile X, tuberous sclerosis, Down syndrome, etc.
Psychiatric disorders	Up to 70% over lifetime	Anxiety (~40%), ADHD (~30–60%), depression (~12–20%), OCD, tic disorders
Epilepsy	~20–30%	Higher in those with co-occurring ID; bimodal onset (early childhood & adolescence)
Sleep disturbances	~50–80%	Insomnia, circadian rhythm abnormalities (↓ melatonin production)
GI symptoms	~30–50%	Constipation, food selectivity, abdominal pain
Motor difficulties	Common	Hypotonia, dyspraxia, motor stereotypies

High Yield — Comorbidity

Always screen for comorbid conditions in ASD. The psychiatric comorbidities (especially anxiety, ADHD, and depression) are often more amenable to treatment than the core ASD features themselves, and treating them can dramatically improve quality of life.

3. Risk Factors

4. Anatomy and Functional Neuroanatomy

Understanding the neuroanatomy helps explain why the clinical features of ASD occur. ASD is fundamentally a disorder of brain connectivity and neural network organisation rather than a single focal lesion.

Region	Abnormality	Functional Consequence
Prefrontal cortex	Altered cortical thickness and columnar organisation	Impaired executive function (planning, cognitive flexibility, working memory) → contributes to rigidity and perseveration
Fusiform gyrus (fusiform face area)	Reduced activation during face processing	Difficulty recognising faces and reading facial expressions → social communication deficits
Amygdala	Early overgrowth (toddlers), then possible atrophy in adults	Abnormal emotional processing, fear conditioning, and social salience detection
Superior temporal sulcus (STS)	Reduced activation	STS is critical for perceiving biological motion, gaze direction, and vocal prosody → poor reading of social cues
Cerebellum	Reduced Purkinje cell numbers, structural anomalies	Motor coordination difficulties, possibly contributes to repetitive behaviours and cognitive processing
Corpus callosum	Often reduced in size	Impaired interhemispheric connectivity
White matter tracts	Abnormal diffusion tensor imaging (DTI) metrics	Reflects aberrant long-range connectivity

5. Etiology and Pathophysiology

ASD etiology is incompletely understood but is best conceptualised as a multifactorial, polygenic condition with contributions from genetic, neurobiological, psychological, and environmental factors ^[2].

5.1 Biological Factors

5.2 Psychological Factors (Cognitive Theories)

These are not "causes" of ASD but rather cognitive frameworks that attempt to explain the pattern of deficits and strengths seen in ASD ^[2]:

Factor	Mechanism
Obstetric complications (prematurity, perinatal hypoxia, low birth weight)	May act as "second hits" on a genetically predisposed brain ^[2]
Maternal valproate use	Disrupts fetal brain development (altered neuronal migration, apoptosis); well-established dose-dependent risk ^[2]
Advanced paternal age	Increased de novo mutations in sperm; altered epigenetic imprinting ^[2]
Prenatal infections	Maternal immune activation → fetal neuroinflammation ^[2]
Maternal migration around pregnancy	?Stress, ?↓immunity to endemic infections, ?vitamin D deficiency ^[2]

The Biopsychosocial Model of ASD

ASD is best understood as arising from polygenic genetic vulnerability interacting with prenatal/perinatal environmental exposures, leading to aberrant neurodevelopmental trajectory (abnormal synaptogenesis, pruning, and connectivity), which produces the cognitive phenotype (impaired ToM, executive dysfunction, WCC), which in turn manifests as the behavioural phenotype (social communication deficits + RRBs). The psychological theories describe how the brain processes information differently; the neurobiology describes why.

6. Classification

ASD (299.00) is a single diagnostic entity with specifiers ^[1]:

Specifier	Options
Severity level	Level 1: "Requiring support"
	Level 2: "Requiring substantial support"
	Level 3: "Requiring very substantial support"
With/without intellectual impairment	e.g., ASD with accompanying intellectual impairment
With/without language impairment	e.g., ASD with accompanying language impairment
Associated conditions	e.g., associated with a known medical/genetic condition (Fragile X, tuberous sclerosis) or environmental factor (valproate exposure)
Associated with another neurodevelopmental, mental, or behavioural disorder	e.g., associated with ADHD, anxiety disorder
With catatonia	A rare but important specifier

Under Pervasive Developmental Disorders (F84) ^[2]:

ICD-10 Code	Diagnosis	Key Features
F84.0	Childhood autism	Classical autism with all 3 domains manifesting before age 3 ^[2]
F84.1	Atypical autism	Does not meet full temporal or symptomatic criteria for childhood autism ^[2]
F84.2	Rett syndrome	Female-only, MECP2 mutation, progressive encephalopathy after 6 months of normal development ^[2]
F84.3	Other childhood disintegrative disorder	Normal development followed by regression of acquired skills ^[2]
F84.4	Overactive disorder with mental retardation and stereotyped movements	Poorly defined category
F84.5	Asperger syndrome	Autistic features WITHOUT delay in language or cognitive development ^[2]
F84.8/9	PDD-NOS	Residual category

7. Clinical Features

The clinical presentation of ASD varies enormously across the spectrum. Features are organised into the two DSM-5 core domains plus associated features. For each feature, the underlying pathophysiological/cognitive basis is explained inline.

These must be present across multiple contexts (not just one setting).

Feature	Description	Pathophysiological Basis
Reduced social approach / sharing of interests	Diminished initiation of social interaction; does not spontaneously share enjoyment or interests with others (e.g., a toddler who finds a bug but doesn't bring it to show a parent)	↓ Social motivation (mesolimbic reward pathway dysfunction) → social stimuli are less intrinsically rewarding → less drive to seek social engagement
Failure of normal conversational turn-taking	One-sided conversations, monologues about topics of interest, difficulty maintaining the "volley" of dialogue	Impaired ToM → cannot gauge what the listener knows/wants to hear; executive dysfunction → difficulty shifting topics; WCC → over-focus on own interest
Reduced sharing of emotions and affect	Flat or incongruent emotional expression; may not respond to others' emotional cues (e.g., does not comfort a crying friend)	Impaired affective ToM + mirror neuron dysfunction → difficulty recognising and resonating with others' emotional states
Abnormal social approach behaviours	May approach others in odd ways (too close, too formal, too blunt)	Impaired understanding of social norms and pragmatic rules

Age-specific manifestations ^[2]:

Infants/toddlers: Reduced social smiling, poor eye contact, lack of anticipatory reaching, absence of joint attention (not following a point, not pointing to share interest — a critical early red flag, typically emerges 9–14 months), lack of showing/bringing objects.
Preschool: Not responsive to other people's feelings; lack of pretend/social play; unable to share pleasure; does not point out objects to another person ^[2].
School-age: Inability to join in play with peers (occasionally disruptive); easily overwhelmed by social stimulation; extreme reactions to invasion of personal space ^[2].
Adolescents: Socially naïve, not as independent as peers; difficulty making and maintaining peer friendships ^[2].

Feature	Description	Pathophysiological Basis
Poor eye contact	Reduced, absent, or unusual eye contact (either avoidance or overly intense staring)	Multiple factors: amygdala hyperactivation in response to direct gaze (gaze feels threatening) + reduced fusiform face area activation (faces are not processed as socially salient) + reduced social reward from faces
Abnormal body language and gestures	Reduced use of pointing, waving, nodding, head-shaking; gestures may be clumsy or absent	Impaired mirror neuron system → difficulty acquiring and using communicative gestures through observation and imitation
Flat, monotonous, or unusual prosody	Speech may be robotic, sing-song, overly formal, or have unusual rhythm/volume	Difficulty modulating suprasegmental features of speech (prosody is a right-hemisphere / subcortical function); reduced understanding of prosodic cues in others (STS underactivation)
Reduced facial expressiveness	Limited range of facial expressions; expressions may be incongruent with emotional context	Mirror neuron dysfunction + impaired emotional regulation
Poor integration of verbal and nonverbal communication	Words say one thing, body language says another; or cannot "read" when someone's words and body language are mismatched	WCC / poor multimodal integration; difficulty integrating information across modalities

Feature	Description	Pathophysiological Basis
Difficulty adjusting behaviour to social context	Same behaviour at a funeral as at a party; too formal with peers, too casual with authorities	Impaired ToM → cannot read contextual social demands; executive dysfunction → difficulty flexibly adapting
Difficulty sharing imaginative play	Absent or reduced pretend play (e.g., does not feed a doll, does not play "house")	Pretend play requires ToM (imagining the doll is "real" and has needs) + creative flexibility
Apparent lack of interest in peers	Preference for solitary play; or desire for friendship but inability to form/maintain it	↓ Social motivation in some; impaired social skills preventing friendship formation in others (different subgroups)
Difficulty understanding unwritten social rules	Does not grasp concepts like personal space, turn-taking in games, "reading the room"	Impaired implicit social learning (relies on explicit teaching of rules that neurotypical children absorb implicitly)

7.2 Domain B: Restricted, Repetitive Patterns of Behaviour, Interests, or Activities (RRBs)

At least 2 of 4 subcategories must be present (currently or by history):

Feature	Description	Pathophysiological Basis
Motor stereotypies	Hand-flapping, finger-flicking, spinning, rocking, toe-walking	Basal ganglia / cortico-striatal circuit dysfunction → repetitive motor patterns; also may serve as self-stimulation ("stimming") to regulate sensory input
Unusual use of objects	Lining up toys in rows, spinning wheels on a car (rather than playing with the whole car), flipping objects	WCC → focus on parts rather than whole; preference for predictable, repetitive sensory input
Echolalia	Immediate (parroting back what was just said) or delayed (repeating phrases from TV shows, books, or past conversations) ^[2]	Language processing differences → gestalt language acquisition (learning language in "chunks" rather than analytically building sentences from words)
Idiosyncratic language	Pronoun reversal (referring to self as "you" or "he/she" beyond age 3) ^[2]; unusual vocabulary for child's age ^[2]; stereotyped phrases	Impaired pragmatic language development; echolalic origin of pronoun reversal (echoes the pronoun used by the speaker, e.g., "Do you want a drink?" → "You want a drink")
Persistent echolalia beyond typical age	Normal toddlers may echo briefly; persistence is atypical ^[2]	As above

Feature	Description	Pathophysiological Basis
Insistence on sameness	Extreme distress at small changes (taking a different route to school, rearranged furniture, food presented differently)	Executive dysfunction (cognitive inflexibility) + anxiety in the face of unpredictability → routines provide predictability and reduce anxiety
Rigid rituals	Must follow exact sequences (e.g., specific bedtime routine, specific order of dressing)	As above; also related to need for predictability in a world that feels chaotic due to impaired social understanding
Difficulty managing change ^[2]	Transitions between activities are especially difficult	Poor cognitive flexibility (prefrontal dysfunction)
Rigid thinking patterns	Black-and-white thinking; difficulty with ambiguity; literal interpretation of language	WCC + executive dysfunction

Feature	Description	Pathophysiological Basis
Circumscribed interests	Intense preoccupation with specific topics (e.g., trains, dinosaurs, weather patterns, licence plates) that is unusual in intensity and depth ^[2]	Altered reward processing → these interests activate the dopaminergic reward system more strongly than social stimuli; WCC → ability to accumulate vast detailed knowledge in narrow domains
Preference for highly specific, narrow interests or hobbies ^[2]	May enjoy collecting, numbering, or listing ^[2]	Local processing bias → satisfaction from cataloguing and systematising
Strong attachment to unusual objects	Carrying the same piece of string, rubber band, or specific object everywhere	Need for sameness + sensory properties of the object
Tendency to talk freely only about specific topics ^[2]	Monologues on favourite subject; difficulty engaging with others' topics	Impaired ToM (doesn't recognise listener's disinterest) + intrinsic reward from the topic

This was newly added in DSM-5 as a formal criterion, reflecting strong research evidence:

Feature	Description	Pathophysiological Basis
Sensory hypersensitivity	Distress from loud noises (covering ears), certain textures (tags on clothing, food textures), bright lights, strong smells	GABAergic E/I imbalance in sensory cortices → reduced sensory gating / filtering → sensory input is experienced as overwhelming
Sensory hyposensitivity	Apparent indifference to pain or temperature; may not notice injuries	Altered sensory processing thresholds; possibly related to endogenous opioid system differences
Unusual sensory seeking	Fascination with spinning objects, lights, water flowing; sniffing objects; visual inspection of objects at unusual angles ^[2]	Seeking specific sensory input that is experienced as pleasurable or calming (self-regulatory function)
Unusual reactions to sensory stimuli ^[2]	Variable — can be hyper or hypo depending on the modality and context	Atypical sensory processing across thalamo-cortical pathways

7.3 Additional Clinical Features and Signs (Not Part of Core Diagnostic Criteria but Important)

7.4 Clinical Clues by Age Group

This is extremely high-yield for recognising ASD at different developmental stages ^[2]:

While ASD is primarily diagnosed through behavioural observation and history, clinical examination may reveal:

Sign	Significance
Macrocephaly (head circumference > 97th centile)	Present in ~20%; reflects accelerated early brain growth
Dysmorphic features	Suggest syndromic ASD (Fragile X: long face, prominent ears, macroorchidism; Tuberous sclerosis: ash-leaf spots, shagreen patches; etc.)
Hypotonia	Common associated motor finding
Absence of pointing / showing / joint attention	Core social communication deficit
Poor eye contact during examination	Not diagnostic in isolation but contributory
Motor stereotypies observed during assessment	Hand-flapping, spinning, repetitive movements
Unusual sensory behaviours	Sniffing, licking, visual inspection at unusual angles
Lack of functional/pretend play during free play observation	Plays repetitively or with parts of objects rather than symbolically
Echolalia or pronoun reversal during language assessment	Language features suggestive of ASD
Skin examination findings	Café-au-lait spots (NF1), ash-leaf macules (tuberous sclerosis), etc. — look for syndromic causes

Pathophysiological Mechanism	Cognitive Theory	Clinical Manifestation
↓ Fusiform face area activation	—	Poor face recognition, reduced gaze
↓ Mesolimbic reward to social stimuli	Social motivation theory	Reduced social initiation, preference for objects over people
Mirror neuron dysfunction	—	Impaired imitation, empathy, gesture use
Amygdala dysfunction	—	Abnormal emotional processing, difficulty reading emotions
STS underactivation	—	Poor reading of gaze, biological motion, prosody
Prefrontal dysfunction	Executive function theory	Perseveration, rigidity, poor planning
Cortico-striatal loop dysfunction	—	Motor stereotypies, rituals
Altered long-range connectivity	Weak central coherence	Local processing bias, islets of ability, difficulty seeing "big picture"
E/I imbalance (GABA/glutamate)	—	Sensory hyper/hyposensitivity, seizure risk
Serotonergic abnormalities	—	Mood/anxiety comorbidity, GI symptoms
Impaired ToM neural network	Theory of mind deficit	Cannot understand others' perspectives, poor pragmatic language

High Yield Summary

Definition: ASD = neurodevelopmental disorder with (1) persistent deficits in social communication/interaction + (2) restricted, repetitive behaviours (RRBs). DSM-5 = single entity; ICD-10 = pervasive developmental disorders.

Epidemiology: ~1% prevalence; M:F ≈ 4-5:1; high comorbidity with ID (~31%), ADHD, anxiety, epilepsy.

Aetiology: Heritability ~80-90%. Polygenic (common SNPs + rare CNVs). Environmental second hits (prematurity, valproate, paternal age). NOT caused by vaccines or parenting.

Pathophysiology: Aberrant synaptic pruning → altered connectivity (↓ long-range, ↑ local) → cognitive phenotype (impaired ToM, executive dysfunction, WCC) → behavioural phenotype.

Key Cognitive Theories: (1) Theory of Mind deficit → social communication problems; (2) Executive function impairment → rigidity, perseveration; (3) Weak Central Coherence → local processing bias, islets of ability.

Core Features — Domain A (Social Communication): Reduced reciprocity, poor nonverbal communication (eye contact, gestures, prosody), difficulty with relationships.

Core Features — Domain B (RRBs): Motor stereotypies, insistence on sameness, circumscribed interests, sensory hyper/hyposensitivity. Need ≥ 2 of 4.

Red Flags (Early): No babbling by 12mo, no gestures by 12mo, no words by 16mo, no 2-word phrases by 24mo, regression at any age, absent joint attention.

Clinical Clues by Age: Preschool (no pretend play, no pointing, language delay), School-age (echolalia, pronoun reversal, can't join play), Adolescent (socially naïve, narrow interests, speech peculiarities).

Active Recall - ASD Definition, Epidemiology, Etiology and Clinical Features

Differential Diagnosis of Autistic Spectrum Disorder (ASD)

The differential diagnosis of ASD is one of the most clinically important steps because many conditions share overlapping features — particularly social difficulties, language delay, repetitive behaviours, or behavioural problems. The key to differentiation is understanding which domains are affected and which are preserved. ASD is unique in that it affects both social communication and restricted/repetitive behaviours simultaneously; most mimics affect only one domain.

Think of it this way: when you see a child with apparent social difficulties or language delay, you need to ask — "Is this truly ASD, or is there another explanation that accounts for the presentation better?"

Condition	Overlapping Features with ASD	Salient Differentiating Features ^[2]	Key Distinguishing Question
Intellectual Disability / Global Developmental Delay (ID/GDD)	Language delay, behavioural difficulties, may appear socially immature	Children with ID/GDD have developmentally appropriate social skills and communication efforts relative to their mental age ^[2]. They want to communicate and interact — they just have limited cognitive resources. In ASD, social communication is impaired disproportionately to overall cognitive level. Note: ASD and ID commonly co-occur (~31%); to make a comorbid diagnosis, social communication must be below what is expected for general developmental level ^[2].	"Does this child's social ability match their overall cognitive ability, or is it worse?"
Language Disorder (Developmental Language Disorder / Specific Language Impairment)	Delayed/absent spoken language, frustration-related behavioural problems	Despite verbal communication difficulties, there is normal non-verbal communication (gestures, pointing, facial expression), normal reciprocal social interactions, normal desire and intent to communicate, and appropriate imaginative play. There are no restricted/repetitive behaviours, interests, or activities ^[2].	"Is the child trying hard to communicate through other means (pointing, gestures, facial expressions) despite their language delay?"
Social (Pragmatic) Communication Disorder (SCD)	Difficulties with social use of language (pragmatics), trouble with conversational rules, understanding non-literal language	SCD is essentially "Domain A without Domain B" — there are social communication deficits but no restricted/repetitive behaviours. If RRBs are present (even historically), the diagnosis is ASD, not SCD. This is a DSM-5 diagnosis created specifically for this boundary ^[2].	"Are there ANY restricted/repetitive behaviours, now or historically?"
Hearing Impairment	Apparent language delay, may not respond to name, may seem to "ignore" others	Distinguished by normal social reciprocity, imaginative play, normal eye contact, and facial expressions indicative of intention to communicate ^[2]. The child shows strong nonverbal communicative intent. Audiological assessment resolves the question.	"Does the child use eye contact, gestures, and facial expressions to communicate despite not responding to sound?"
ADHD	Impaired social functioning (due to impulsivity, inattention), difficulty maintaining friendships, may seem not to listen	Social impairment in ADHD arises from impulsivity and poor self-control rather than from fundamental deficits in social understanding ^[2]. Children with ADHD have normal pragmatic language skills, normal nonverbal social behaviour, and normal imaginary play ^[2]. The social impairment is usually milder and qualitatively different. Note: ADHD and ASD frequently co-occur (30-60%); DSM-5 now allows dual diagnosis ^[2].	"Can this child engage in reciprocal social interaction when they are focused and calm?"
OCD	Repetitive behaviours, ritualistic patterns, insistence on things being "just right"	In OCD, individuals find their repetitive thoughts/behaviours distressing (ego-dystonic), whereas individuals with ASD typically do not experience their RRBs as distressing (ego-syntonic — they find them comforting or neutral) ^[2]. Social, communication, and language skills are usually normal in OCD ^[2].	"Does the child find their repetitive behaviours distressing and want to stop them?"
Schizophrenia	Social withdrawal, unusual behaviours, restricted affect, odd beliefs/interests	The prodromal state of psychosis may be associated with social impairment and atypical interests/beliefs ^[2]. Key differentiator: look for positive symptoms of psychosis (delusions, hallucinations) ^[2]. Schizophrenia has a later onset (typically late adolescence/early adulthood), episodic course, and premorbid social functioning was usually normal. DSM-5 notes: if there is a history of ASD, the additional diagnosis of schizophrenia requires prominent delusions or hallucinations for at least 1 month ^[2].	"Is there evidence of delusions, hallucinations, or formal thought disorder? Was premorbid development normal?"
Tic Disorder / Stereotypic Movement Disorder	Repetitive, purposeless motor behaviours (tics, stereotypies)	Social, language, and communication skills are typically normal ^[2]. Tics are brief, rapid, involuntary movements often preceded by premonitory urge; stereotypic movements are rhythmic and patterned but occur without the broader ASD social/communication phenotype.	"Are social communication skills intact?"
Selective Mutism	Apparent failure to communicate in certain settings, may appear socially withdrawn	The child is capable of normal speech and social interaction in comfortable settings (e.g., at home) but fails to speak in specific social situations (e.g., school). This is an anxiety-based condition. Nonverbal communication may be preserved or also inhibited. No RRBs.	"Does this child speak normally in at least one setting?"
Reactive Attachment Disorder (RAD)	Social withdrawal, reduced emotional responsiveness, lack of social reciprocity	Results from severe early deprivation/neglect. Distinguished by history of pathological care, and symptoms can improve substantially with placement in a nurturing environment. No RRBs. Language development is often delayed but pragmatic skills are present once trust develops.	"Is there a history of severe deprivation, neglect, or institutional care?"
Disinhibited Social Engagement Disorder (DSED)	Indiscriminate friendliness, unusual social approach behaviour	Also results from pathological early care. The child approaches strangers with no appropriate reticence — the opposite of ASD's reduced social approach, but can be confused because both involve "abnormal social behaviour." No RRBs.	"Is the social abnormality indiscriminate over-friendliness rather than social withdrawal/qualitative impairment?"
Childhood Disintegrative Disorder / Regression	Loss of previously acquired skills, development of stereotypies	Distinguished from ASD by a prolonged period (> 2 years) of clearly normal development before dramatic regression in multiple domains. Now subsumed under ASD in DSM-5 (with specifier "with loss of established skills") but should prompt investigation for neurodegenerative/metabolic conditions (e.g., Rett syndrome, Sanfilippo syndrome, neuronal ceroid lipofuscinosis).	"Was development clearly normal for > 2 years before regression?"
Anxiety Disorders (Social Anxiety Disorder)	Social avoidance, difficulty with peer relationships	In social anxiety, the child understands social cues and wants social connection but is paralysed by fear of negative evaluation. Social cognition (ToM) is intact or even heightened (hyper-mentalising). No RRBs. Pragmatic language is intact.	"Does the child understand social situations but avoid them due to anxiety, or does the child genuinely not understand social cues?"
Depression	Social withdrawal, reduced communication, flat affect	Later onset, episodic course. Social withdrawal is secondary to low mood and anhedonia rather than fundamental social communication impairment. Pre-morbid social functioning was typically normal. No RRBs.	"Was social functioning previously normal, and did it decline in association with mood changes?"

The Two Critical Questions in DDx of ASD

When faced with a child who might have ASD, always ask:

"Is social communication impaired disproportionately to overall developmental level?" → If social skills match cognitive level, think ID/GDD rather than ASD.
"Are there restricted, repetitive behaviours?" → If absent, consider language disorder, SCD, hearing impairment, selective mutism, RAD, or anxiety disorders instead.

If both answers are "yes," ASD is the most likely diagnosis. If only one is "yes," look carefully at alternatives.

Key Differentiating Concepts — Explained from First Principles

Feature	ASD	ID	Language Disorder	ADHD	OCD	Schizophrenia
Social communication deficit	++ (disproportionate)	+ (proportional to cognitive level)	Verbal only (nonverbal intact)	Mild, due to impulsivity	Normal	Late-onset, with psychotic features
RRBs	++	- or mild	-	-	+ (ego-dystonic)	- (may have stereotypies in chronic)
Imaginative play	Impaired	Proportional to mental age	Normal	Normal	Normal	May be impoverished
Nonverbal communication	Impaired	Proportional	Normal / compensatory	Normal	Normal	May be flat
Onset	Early developmental	Early	Early	Early	Variable	Late adolescence/adulthood
Course	Continuous	Continuous	May improve	Continuous	Episodic/chronic	Episodic
Distress from repetitive behaviours	No (ego-syntonic)	N/A	N/A	N/A	Yes (ego-dystonic)	N/A

High Yield Summary — Differential Diagnosis of ASD

Core differentiating principle: ASD = social communication deficit (disproportionate to cognitive level) PLUS restricted/repetitive behaviours. Most mimics affect only one domain.

vs ID: Social skills match cognitive level in ID; disproportionately impaired in ASD. Can co-occur — need social communication below expected for developmental level.

vs Language Disorder: Nonverbal communication and social intent are NORMAL in language disorder. No RRBs. Imaginative play preserved.

vs Hearing Impairment: Normal social reciprocity, eye contact, imaginative play despite not hearing.

vs ADHD: Social impairment in ADHD is due to impulsivity/inattention, not fundamental social cognition deficit. Normal pragmatic language, nonverbal behaviour, and imaginative play. Frequently co-occurs with ASD.

vs OCD: OCD rituals are ego-dystonic (distressing); ASD RRBs are ego-syntonic (comforting). Social/communication skills normal in OCD.

vs Schizophrenia: Later onset, episodic, positive psychotic symptoms distinguish it. DSM-5 requires prominent delusions/hallucinations for ≥ 1 month to add schizophrenia diagnosis to existing ASD.

vs Social Anxiety: Child with social anxiety understands social cues but fears negative evaluation; child with ASD doesn't intuitively understand social cues.

Always screen for comorbidities — ADHD, anxiety, ID, epilepsy, genetic syndromes — because these are often more treatable than core ASD.

Active Recall - Differential Diagnosis of ASD

References

^[2] Senior notes: ryanho-psych.md (Section 12.2 Autistic Spectrum Disorder — D/dx, Diagnostic criteria, Clinical features)

Diagnostic Criteria

ASD is a clinical diagnosis — there is no blood test, brain scan, or single investigation that confirms it. The diagnosis rests on careful behavioural observation and developmental history, judged against standardised criteria. Let's go through both major classification systems, then discuss the practical diagnostic algorithm and investigations.

DSM-5 Diagnostic Criteria for Autism Spectrum Disorder (299.00)

The DSM-5 criteria are the current gold standard and are what you need to know cold for exams ^[2]:

Criterion A: Persistent deficits in social communication and social interaction across multiple contexts, as manifested by ALL 3 of the following (currently or by history) ^[2]:

Deficits in social-emotional reciprocity — ranging from abnormal social approach and failure of normal back-and-forth conversation, to reduced sharing of interests, emotions, or affect, to failure to initiate or respond to social interactions ^[2].
Deficits in nonverbal communicative behaviours used for social interaction — ranging from poorly integrated verbal and nonverbal communication, to abnormalities in eye contact and body language or deficits in understanding and use of gestures, to a total lack of facial expressions and nonverbal communication ^[2].
Deficits in developing, maintaining, and understanding relationships — ranging from difficulties adjusting behaviour to suit various social contexts, to difficulties in sharing imaginative play or in making friends, to absence of interest in peers ^[2].

Why ALL 3? Because ASD is defined by a pervasive social communication deficit — it's not just "shy" (which would affect only approach) or "blunt" (which would affect only reciprocity). The requirement for all three subcategories ensures that the social impairment is truly pervasive across different aspects of social functioning.

Criterion B: Restricted, repetitive patterns of behaviour, interests, or activities, as manifested by ≥ 2 of the following 4 (currently or by history) ^[2]:

Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys, flipping objects, echolalia, idiosyncratic phrases) ^[2].
Insistence on sameness, inflexible adherence to routines, or ritualised patterns of verbal or nonverbal behaviour (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food) ^[2].
Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests) ^[2].
Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement) ^[2].

Why ≥ 2 of 4? Because RRBs are heterogeneous — some individuals have prominent motor stereotypies but no sensory issues; others have intense circumscribed interests but no insistence on sameness. Requiring at least 2 subcategories ensures the pattern is sufficiently broad to distinguish ASD from isolated stereotypic movement disorder or isolated sensory processing differences.

Criterion C: Symptoms must be present in the early developmental period ^[2].

But may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life ^[2].
Why this caveat? Many individuals (especially females, those with higher IQ, and those with good language) develop "camouflaging" strategies that mask their difficulties. A university student who was a quiet loner in primary school but coped may only "decompensate" when social demands intensify (e.g., entering the workforce, forming romantic relationships). The symptoms were always there — they just weren't visible until demands exceeded capacity.

Criterion D: Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning ^[2].

Criterion E: These disturbances are not better explained by intellectual disability (ID) or global developmental delay (GDD) ^[2].

To make a comorbid diagnosis of ASD with ID, social communication should be below that expected for general developmental level ^[2].
Why this criterion? It prevents over-diagnosis of ASD in children whose social difficulties are entirely accounted for by their cognitive limitations. You need to demonstrate that the social impairment is disproportionate to their overall development.

Level	Social Communication	Restricted, Repetitive Behaviours
Level 3: "Requiring very substantial support"	Severe deficits; very limited initiation; minimal response to social overtures	Inflexibility, extreme difficulty coping with change; RRBs markedly interfere with functioning; great distress changing focus or action
Level 2: "Requiring substantial support"	Marked deficits; limited initiation; reduced or abnormal response to social overtures; even with supports in place	Inflexibility, difficulty coping with change; RRBs frequent enough to be obvious to casual observer; distress and difficulty changing focus
Level 1: "Requiring support"	Without supports, deficits cause noticeable impairments; difficulty initiating; may appear to have decreased interest in social interactions; atypical or unsuccessful responses	Inflexibility causes significant interference; difficulty switching between activities; problems of organisation and planning hamper independence

Feature	DSM-5	ICD-10
Name	Autism Spectrum Disorder	Childhood Autism (plus subtypes)
Core domains	2 (social communication + RRBs)	3 (social interaction + communication + RRBs)
Domain A requirement	All 3 subcategories	All domains impaired
Domain B requirement	≥ 2 of 4 subcategories	Present (no minimum subcategory count specified)
Sensory criterion	Explicitly included (B4)	Not explicitly listed
Age of onset	"Early developmental period" (flexible)	Before age 3 years (strict)
Subtypes	None — single spectrum with specifiers	Multiple subtypes (childhood autism, Asperger, atypical autism, etc.)
Language	Not a diagnostic criterion — used as specifier	Part of communication domain
ID exclusion	Not better explained by ID (but can co-occur if social communication below expected for developmental level)	Not explicitly stated

Diagnostic Algorithm

Assessment: The Diagnostic Evaluation in Detail

The Core Assessment (The Most Important Component)

As stated clearly in the senior notes: "Clinical interview and assessment (most important)" ^[2]. The diagnosis of ASD is made by expert clinical judgement based on a comprehensive evaluation, not by any single test. The assessment typically involves a multidisciplinary team using standardised assessment in a day hospital assessment setting ^[2].

This is the foundation of the diagnostic assessment. You are trying to establish:

Domain	What to Ask	Why
Early development	Pregnancy complications, gestational age, birth history, APGAR, neonatal period	Identify perinatal risk factors
Developmental milestones	Motor (sitting, walking), language (babbling, first words, phrases), social (smiling, joint attention, pointing, pretend play)	Identify delays and the temporal pattern of symptom emergence
Regression	Did the child lose previously acquired skills (words, social behaviours)? At what age?	~25-30% of ASD cases show regression, usually 15-24 months; severe regression warrants investigation for neurodegenerative conditions
Social communication (Criterion A)	How does the child interact with family members, peers? Eye contact? Response to name? Sharing enjoyment? Pointing? Imitation?	Map symptoms to DSM-5 Criterion A subcategories
RRBs (Criterion B)	Repetitive movements? Rituals? Insistence on sameness? Intense interests? Sensory responses?	Map symptoms to DSM-5 Criterion B subcategories
Functional impact (Criterion D)	How do these difficulties affect daily life, learning, family?	Establish clinical significance
Family history	ASD, intellectual disability, language delay, psychiatric conditions in first/second-degree relatives	Strong genetic component; familial recurrence risk
Medical history	Seizures, sleep problems, GI symptoms, hearing/vision concerns, genetic conditions	Identify comorbidities and aetiological factors
Behavioural concerns	Self-injury, aggression, tantrums, sleep, feeding, toileting	Associated features that need management

These are not "diagnostic tests" — they are structured tools that support clinical judgement:

Instrument	Type	What It Does	Key Details
ADOS-2 (Autism Diagnostic Observation Schedule, 2nd Edition)	Semi-structured, standardised direct observation	Gold standard observational assessment. The clinician creates "social presses" (opportunities for the child to demonstrate social communication) and rates the child's responses. Different modules for different ages/language levels.	Module 1: Pre-verbal/single words; Module 2: Phrase speech; Module 3: Fluent speech (children); Module 4: Fluent speech (adolescents/adults). Provides calibrated severity scores. ~40-60 minutes.
ADI-R (Autism Diagnostic Interview — Revised)	Structured parent/caregiver interview	Gold standard interview. Systematically probes for ASD symptoms across development. Covers reciprocal social interaction, communication, RRBs. Algorithm generates scores mapped to ICD-10/DSM-IV domains.	~1.5-3 hours. Best used for research; sometimes abbreviated in clinical practice.
ADOS-2 + ADI-R combination	—	Using both provides the most comprehensive assessment (observation + history) and is the research gold standard. In clinical practice, at least one should be used.	—
M-CHAT-R/F (Modified Checklist for Autism in Toddlers — Revised with Follow-Up)	Parent-report screening questionnaire	Level 1 screening tool for toddlers aged 16-30 months. 20 yes/no questions. Follow-up interview reduces false positives.	Sensitivity ~85%, specificity ~99% after follow-up. NOT a diagnostic tool — positive screen requires referral for comprehensive assessment.
SCQ (Social Communication Questionnaire)	Parent-report screening questionnaire	40-item screening tool for ages 4+. Based on ADI-R. Lifetime and current forms. Cutoff score ≥ 15 suggests need for further evaluation.	Quick (~10 min). Good for initial screening.
SRS-2 (Social Responsiveness Scale, 2nd Edition)	Parent/teacher-report rating scale	Quantifies severity of social communication deficits across a continuous dimension. Not diagnostic but useful for tracking.	Available for ages 2.5 through adult.
CARS-2 (Childhood Autism Rating Scale, 2nd Edition)	Clinician-rated observation scale	15-item scale rated during observation. Provides severity rating (mild-moderate, severe). Quick to administer.	Less specific than ADOS-2 but useful in resource-limited settings.

ADOS-2 — The 'Gold Standard' Observation Tool

Think of the ADOS-2 as creating a standardised "social laboratory." The examiner deliberately creates situations that would normally elicit social communication behaviours — for example:

Blowing up a balloon and then putting it just out of reach (does the child request? point? make eye contact?)
Starting a silly game and then suddenly stopping (does the child try to re-engage the examiner?)
Showing the child an interesting toy and gauging their response (do they share enjoyment? look back and forth between the toy and the examiner?)

The child's responses (or lack thereof) are rated on standardised algorithms that map onto DSM-5 domains.

Supporting Assessments (Post-Diagnostic)

These do not diagnose ASD but are essential for comprehensive evaluation ^[2]:

Test	Ages	What It Measures	Why It Matters
Wechsler scales (WPPSI for preschool, WISC for school-age, WAIS for adults)	2.5+	Full-scale IQ, Verbal Comprehension, Perceptual Reasoning, Working Memory, Processing Speed	Determines presence/severity of intellectual impairment (DSM-5 specifier); identifies cognitive profile (often uneven in ASD — may show VCI-PRI discrepancy); guides educational placement
Bayley Scales of Infant Development	0-42 months	Cognitive, language, motor, social-emotional, adaptive behaviour	For very young or developmentally delayed children
Non-verbal IQ tests (Leiter, Ravens)	Various	Non-verbal cognitive ability	Essential for non-verbal or minimally verbal children with ASD who cannot engage with verbally-loaded IQ tests — prevents underestimation of cognitive ability

Why an uneven IQ profile matters: Many individuals with ASD show a characteristic pattern of relative strengths in perceptual reasoning (block design, matrix reasoning — tasks benefiting from local processing/WCC) and relative weaknesses in verbal comprehension or processing speed. This profile supports the diagnosis and guides intervention.

Domain	What Is Assessed	Clinical Significance
Receptive language	Understanding of words, sentences, instructions, complex language	Often more impaired than expressive language in ASD (receptive > expressive delay) ^[2]; guides intervention targets
Expressive language	Vocabulary, grammar, sentence construction	Determines language level specifier
Pragmatic language	Social use of language: conversational rules, topic maintenance, narrative, understanding non-literal language	The hallmark language deficit in ASD — pragmatic difficulties even when structural language is intact
Speech	Articulation, fluency, voice	May have co-occurring speech sound disorder
Augmentative and alternative communication (AAC) needs	Whether the child would benefit from PECS, sign language, communication devices	For minimally verbal children

Domain	What Is Assessed	Clinical Significance
Sensory profile (e.g., Sensory Profile 2)	Sensory processing patterns across modalities	Identifies sensory hyper/hyposensitivities; guides sensory strategies and environmental modifications
Fine motor skills	Handwriting, manipulation, dexterity	Dyspraxia/motor difficulties common in ASD; impacts school performance
Adaptive behaviour (e.g., Vineland Adaptive Behavior Scales)	Communication, daily living skills, socialisation, motor skills in real-world settings	Adaptive function often lower than IQ in ASD; critical for determining support needs and educational placement
Self-care skills	Dressing, feeding, toileting	Identifies areas needing intervention

Remember: there is no diagnostic biomarker for ASD. Medical investigations are performed to:

Identify treatable comorbid conditions (hearing loss, epilepsy, metabolic disorders)
Identify aetiological factors (genetic syndromes)
Exclude medical mimics

Investigation	Indication	Key Findings / Interpretation
Audiological assessment (OAE, ABR, behavioural audiometry)	All children undergoing ASD evaluation	Rule out hearing impairment as a cause of apparent social/communication difficulties. Even partial hearing loss can mimic some ASD features. Must be done before concluding that communication deficits are due to ASD.
Genetic testing	Recommended for all children with confirmed ASD	—
— Chromosomal microarray (CMA)	First-tier genetic test	Detects copy number variants (CNVs) — deletions and duplications. Diagnostic yield ~10-20% in ASD. May identify 16p11.2, 15q11-13, 22q11.2, 22q13.3 (Phelan-McDermid) and other pathogenic CNVs.
— Fragile X testing (FMR1 trinucleotide repeat)	All children with ASD + ID (especially males)	Most common single-gene cause of ASD and ID. Positive result has implications for genetic counselling (X-linked).
— Whole exome sequencing (WES) / Whole genome sequencing (WGS)	Increasingly recommended, especially if CMA negative and clinical suspicion high; syndromic features present	Detects single nucleotide variants (SNVs) and small insertions/deletions. Higher diagnostic yield than CMA alone (~10-30% additional). Identifies mutations in genes like SHANK3, CHD8, PTEN, SCN1A.
— Targeted gene testing	If clinical features suggest specific syndrome (e.g., MECP2 for Rett syndrome, PTEN for macrocephaly + ASD, TSC1/2 for tuberous sclerosis)	Confirms specific syndromic diagnosis; implications for medical management and surveillance.
EEG	If clinical suspicion of seizures (staring spells, regression, unusual episodic behaviours); not routine	Epilepsy occurs in ~20-30% of ASD (higher with co-occurring ID). May show epileptiform discharges. Important: electrical status epilepticus in sleep (ESES) can cause regression mimicking ASD (Landau-Kleffner syndrome).
MRI Brain	Not routine. Indicated if: macrocephaly/microcephaly, focal neurological signs, regression, tuberous sclerosis suspected, seizures	May show structural anomalies (tuberous sclerosis: cortical tubers, subependymal nodules; brain malformations). Not useful as a diagnostic test for "idiopathic" ASD.
Metabolic screening	If regression, failure to thrive, organomegaly, unusual features, consanguinity, or specific clinical suspicion	May include plasma amino acids, urine organic acids, acylcarnitine profile, mucopolysaccharide screen. Metabolic disorders are rare causes of ASD phenocopy (e.g., PKU, Smith-Lemli-Opitz, creatine deficiency syndromes).
Lead level	If pica behaviour or environmental exposure risk	Lead poisoning can cause developmental regression and behavioural disturbance
Thyroid function	If clinical features suggest hypothyroidism; more relevant in Down syndrome	Untreated hypothyroidism can impair development
Wood's lamp examination	If tuberous sclerosis suspected	Ash-leaf macules (hypomelanotic macules) fluoresce under UV light; tuberous sclerosis is associated with ASD in ~50%
Vision assessment	If concerns about visual behaviour	Rule out visual impairment; cortical visual impairment can co-occur with ASD

When to Order Genetic Testing

Current guidelines (ACMG, AAP) recommend chromosomal microarray as a first-tier test for ALL children diagnosed with ASD, regardless of the presence of dysmorphic features. The rationale:

~10-20% will have a pathogenic CNV identified
Even "non-syndromic" appearing children may have identifiable genetic causes
Results change genetic counselling (recurrence risk for siblings)
Some genetic findings have medical surveillance implications (e.g., PTEN → cancer surveillance; TSC → renal/cardiac monitoring)
Increasingly, WES/WGS is also being recommended as a first- or second-tier test given falling costs and higher yield

EEG and MRI Are NOT Routine

A very common mistake is ordering EEG and MRI Brain on every child diagnosed with ASD. These are not routine and should only be performed when there is a specific clinical indication (seizures, regression, focal signs, macrocephaly, syndromic features). In the absence of these indications, the yield is very low and the procedures can be distressing for the child (especially MRI, which may require sedation).

The exception: if there is language regression (loss of previously acquired words, especially around 18-24 months), EEG should be strongly considered to rule out Landau-Kleffner syndrome (acquired epileptic aphasia with ESES pattern on sleep EEG) — a treatable condition.

The diagnostic assessment integrates multiple sources of information:

Source	Weight	Role
Clinical judgement (expert clinician)	Highest	The final arbiter. No instrument replaces expert clinical assessment.
Developmental history (parents/caregivers)	Very high	Only source for early development, regression, symptom onset. Parents know their child best.
Direct observation (ADOS-2 / clinical observation)	Very high	Shows current presentation in a standardised context. A child may behave differently in clinic than at home/school.
Standardised instruments (ADOS-2, ADI-R, etc.)	High	Structure the assessment, ensure systematic coverage, provide severity metrics. But can be false-negative (especially in high-masking females or very young children).
Collateral information (school reports, teacher questionnaires)	Moderate-High	Critical for assessing behaviour across settings (Criterion A requires deficits "across multiple contexts").
Cognitive/language/OT assessments	Moderate	Characterise the profile, identify comorbidities, guide intervention — but do not diagnose ASD themselves.
Medical investigations	Low for ASD diagnosis; variable for aetiology	Do not diagnose ASD. Identify comorbidities, aetiological factors, and treatable conditions.

The diagnosis is ultimately a pattern recognition exercise by an experienced clinician who synthesises all available data against the DSM-5/ICD criteria. There is no single score on any instrument that "confirms" ASD — and equally, a "negative" ADOS-2 does not rule it out if the clinical picture is otherwise compelling.

High Yield Summary — Diagnosis of ASD

DSM-5 Criteria: Criterion A (all 3 subcategories: social-emotional reciprocity + nonverbal communication + relationships) + Criterion B (≥ 2 of 4: stereotypies + sameness + fixated interests + sensory) + Criterion C (early developmental period) + Criterion D (functional impairment) + Criterion E (not better explained by ID/GDD).

ICD-10: 3 domains (social interaction + communication + RRBs), onset before age 3.

Assessment is multidisciplinary ^[2]: clinical interview and assessment is MOST IMPORTANT. Day hospital assessment by MDT. Includes education assessment, IQ test, OT assessment, speech therapist assessment ^[2].

Gold standard instruments: ADOS-2 (observation) and ADI-R (parent interview). Screening: M-CHAT-R/F (toddlers 16-30 months).

Medical investigations: Audiological assessment (ALL children); chromosomal microarray (ALL confirmed ASD); Fragile X testing (ASD + ID); EEG and MRI only if specific indication (seizures, regression, focal signs, macrocephaly); metabolic screen if regression or syndromic features.

No biomarker exists — ASD remains a clinical diagnosis based on expert judgement integrating history, observation, and standardised assessment.

Active Recall - ASD Diagnostic Criteria, Algorithm, and Investigations

Management of Autistic Spectrum Disorder (ASD)

Non-Pharmacological Interventions (The Mainstay of ASD Management)

Non-pharmacological interventions are always the first-line and foundation of ASD management. Medications are adjuncts only ^[2].

1. Behavioural Interventions [2]

What it is: ABA is a systematic approach based on principles of operant conditioning (Skinner). Desired behaviours are reinforced (positive reinforcement), and maladaptive behaviours are reduced through structured techniques. EIBI is ABA delivered intensively (20–40 hours/week) to young children (typically < 5 years).
Why it works from first principles: Children with ASD do not learn social and communication skills implicitly through observation and social immersion the way neurotypical children do (due to impaired social motivation, mirror neuron dysfunction, and theory of mind deficits). ABA breaks down complex social behaviours into small, teachable components and explicitly teaches each one through structured practice and reinforcement. It essentially creates an explicit learning pathway to replace the impaired implicit learning pathway.
Evidence: The strongest evidence base of any ASD intervention. Meta-analyses show improvements in IQ, language, adaptive behaviour, and social skills, especially when started before age 3.
Key techniques within ABA:
- Discrete Trial Training (DTT): Structured, one-to-one teaching in a controlled setting. Teacher gives an instruction → child responds → consequence (reinforcement or correction). Repeated systematically.
- Natural Environment Teaching (NET): Uses naturally occurring situations (playtime, mealtimes) to teach skills in context, improving generalisation.
- Pivotal Response Training (PRT): Targets "pivotal" areas (motivation, self-management, responsiveness to multiple cues) that produce cascading improvements across many behaviours.
Indication: All young children with ASD, especially those with significant developmental delays. The earlier and more intensive, the better.
Limitations/Controversies: Very resource-intensive (expensive, time-consuming). Some autistic self-advocates criticise overly rigid ABA as attempting to enforce "neurotypical" behaviour at the cost of the child's wellbeing; modern ABA has evolved towards more naturalistic, child-led approaches. Quality of the ABA provider matters enormously.

2. Communication Interventions

3. Educational Support [2]

4. Family Support [2]

This is a cornerstone that is often under-emphasised in medical education but is critical in clinical practice:

5. Other Interventions [2]

Pharmacological Interventions [2]

Cardinal Rule

No medications cure ASD or treat its core symptoms ^[2]. All pharmacotherapy is symptom-targeted for comorbid or associated features. Always combine with non-pharmacological interventions.

The approach is: identify the target symptom → choose the appropriate medication → monitor response and side effects → adjust or discontinue ^[2].

Medication	Details	Mechanism	Indication	Key Side Effects / Monitoring
Risperidone ("risper-i-done" — an atypical/second-generation antipsychotic)	FDA-approved for irritability associated with ASD in children aged 5-16 years ^[2]	D2 and 5-HT2A receptor antagonism → reduces aggression, tantrums, self-injury by modulating dopaminergic and serotonergic pathways in the mesolimbic and mesocortical circuits	Significant irritability, aggression, tantrums, self-injurious behaviour not responding to behavioural interventions ^[2]	Weight gain (significant — metabolic syndrome risk), sedation, hyperprolactinaemia (galactorrhoea, gynaecomastia, menstrual irregularities), extrapyramidal symptoms (EPS), metabolic monitoring required (weight, BMI, fasting glucose, lipids, prolactin). Tardive dyskinesia risk with long-term use.
Aripiprazole (Abilify — "a-rip-IP-ra-zole")	FDA-approved (endorsed by FDA) for irritability associated with ASD in children aged 6-17 years ^[2]	Partial D2 agonist and 5-HT2A antagonist. Acts as a "dopamine stabiliser" — reduces dopaminergic activity where it is excessive (reducing aggression/irritability) but maintains activity where it is needed.	Same as risperidone ^[2]	Weight gain (less than risperidone but still significant), akathisia (restlessness — can be distressing and misinterpreted as worsening agitation), insomnia, nausea, EPS. Lower prolactin elevation risk than risperidone. Metabolic monitoring still required.

Why atypical antipsychotics for irritability? Irritability and aggression in ASD are thought to involve dysregulation of dopaminergic and serotonergic circuits (particularly mesolimbic and orbitofrontal pathways). Blocking D2 receptors dampens the excessive dopaminergic drive behind aggression, while 5-HT2A blockade further modulates mood and impulse control. Aripiprazole's partial agonism makes it a "gentler" modulator.

Important prescribing principles:

Always try behavioural interventions first — medication is for when behavioural approaches alone are insufficient.
"Start low, go slow": Begin at the lowest dose and titrate gradually.
Regular review: Attempt dose reduction or discontinuation periodically to assess ongoing need.
Monitor metabolic parameters: Weight, height, BMI, fasting glucose, fasting lipids at baseline, 3 months, then at least 6-monthly.

Contraindications / Cautions:

Known hypersensitivity
Caution in patients with diabetes or metabolic syndrome (worsened by weight gain)
Caution with QTc-prolonging medications (risperidone can prolong QTc)
Avoid in neuroleptic malignant syndrome history

Comorbid ADHD occurs in 30-60% of individuals with ASD ^[2]. Treatment follows standard ADHD guidelines but with additional caution:

Medication	Details	Mechanism	Indication	Key Considerations in ASD
Methylphenidate (Ritalin, Concerta)	First-line stimulant for ADHD	Blocks dopamine and noradrenaline reuptake in the prefrontal cortex → improves executive function, attention, and impulse control	ADHD symptoms in ASD (high energy levels, inability to focus) ^[2]	Less effective in ASD+ADHD than in ADHD alone (~50% response rate vs ~70%). Higher rate of side effects in ASD: irritability, emotional lability, social withdrawal, tics, appetite suppression, insomnia. Start at lower doses than in ADHD alone.
Atomoxetine (Strattera)	Non-stimulant; selective noradrenaline reuptake inhibitor (NRI)	Increases noradrenaline in prefrontal cortex → improves attention and executive function	Alternative when stimulants are ineffective, poorly tolerated, or contraindicated; when comorbid anxiety is present (atomoxetine may also help anxiety)	GI upset, sedation, mood changes. Takes 4-6 weeks for full effect. Advantage: no abuse potential, continuous coverage (no wearing off).
Guanfacine (Intuniv)	Alpha-2A adrenergic agonist	Stimulates alpha-2A receptors in prefrontal cortex → strengthens prefrontal network signalling, improving attention and reducing hyperarousal	Useful when impulsivity/hyperactivity predominates; good adjunct to stimulants	Sedation, hypotension, bradycardia. Useful for managing hyperarousal, sleep onset difficulties, and tic-related ADHD.
Clonidine	Alpha-2 adrenergic agonist (less selective than guanfacine)	Similar to guanfacine	Sometimes used for hyperactivity, sleep, and tics	More sedating than guanfacine; hypotension risk; rebound hypertension if stopped abruptly.

Contraindications for methylphenidate: Uncontrolled hypertension, structural cardiac disease, pheochromocytoma, hyperthyroidism, concurrent MAOI use, severe anxiety (stimulants may worsen), psychosis, tic disorders (relative).

Medication	Details	Mechanism	Indication	Key Considerations in ASD
SSRIs (Fluoxetine, Sertraline, Escitalopram)	Selective serotonin reuptake inhibitors	Block serotonin reuptake at the presynaptic terminal → increase serotonergic transmission → improve mood, reduce anxiety, reduce obsessional/repetitive behaviours	Comorbid anxiety disorders, depression, or obsessive-compulsive features ^[2]	Behavioural activation (agitation, restlessness, disinhibition) is more common in ASD than in neurotypical individuals. Start at VERY low doses and titrate slowly. Monitor for suicidality in adolescents (black box warning). SSRIs may help control of repetitive behaviour in some cases ^[2].
Fluoxetine	Most studied SSRI in children/adolescents	As above	FDA-approved for depression (age 8+) and OCD (age 7+) in general paediatric population; used off-label for anxiety/repetitive behaviours in ASD	Long half-life (good for adherence); activating profile; drug interactions via CYP2D6 inhibition.
Sertraline	Also well-studied	As above	Similar indications	Shorter half-life; fewer drug interactions; GI side effects common.

Why SSRIs for repetitive behaviours? Serotonergic abnormalities are well-documented in ASD (hyperserotonemia). The repetitive behaviours in ASD share neurobiological overlap with OCD (cortico-striatal-thalamo-cortical circuit dysfunction). SSRIs modulate this circuit via serotonergic enhancement. However, the evidence for SSRIs reducing core RRBs in ASD is mixed — they are more consistently helpful for comorbid anxiety/OCD/depression ^[2].

Contraindications for SSRIs: Concurrent MAOI use (serotonin syndrome risk), known hypersensitivity, caution in bipolar disorder (can precipitate mania).

Sleep problems affect 50-80% of children with ASD and significantly impact daytime behaviour, learning, and family QoL.

Intervention	Details	Mechanism	Indication
Sleep hygiene	Consistent bedtime, dark/quiet room, screen reduction before bed, regular wake time, sensory-comfortable bedding	Reinforces circadian rhythm entrainment; reduces sensory-driven wakefulness	First-line for all sleep problems
Melatonin	Exogenous melatonin (0.5-10 mg at bedtime)	Individuals with ASD have documented abnormalities in melatonin synthesis (reduced melatonin levels, altered ASMT gene). Exogenous melatonin restores circadian signalling and promotes sleep onset.	Sleep onset insomnia refractory to sleep hygiene. Well-studied in ASD. Generally safe, well-tolerated. FDA does not regulate as drug (classified as supplement in US); available on prescription in HK.
Prolonged-release melatonin (Slenyto — paediatric formulation)	EMA-approved for insomnia in ASD (ages 2-18)	Addresses both sleep onset and sleep maintenance (delayed release maintains melatonin levels through the night)	Sleep onset + sleep maintenance difficulties

Target Symptom	First-Line Medication	Key Notes
Irritability / Aggression	Risperidone or Aripiprazole (FDA-approved) ^[2]	Monitor metabolic parameters; try behavioural interventions first
ADHD symptoms	Methylphenidate (first-line stimulant); atomoxetine or guanfacine (non-stimulant alternatives) ^[2]	Lower efficacy and higher side effect rate in ASD than ADHD alone
Anxiety / Depression	SSRIs (fluoxetine, sertraline) ^[2]	Start low, go slow; monitor for behavioural activation; may help repetitive behaviours
Repetitive behaviours	SSRIs (limited evidence); behavioural interventions preferred ^[2]	Evidence is mixed for SSRIs targeting RRBs specifically
Sleep disturbance	Melatonin (after sleep hygiene optimisation)	Well-studied in ASD; good safety profile
Seizures	Standard AEDs per seizure type	Avoid valproate in females of childbearing age
Self-injury	Behavioural approach first; risperidone/aripiprazole if severe	Functional assessment of behaviour is essential before medication

Understanding the local service landscape is important for clinical practice:

Service	Role	Age Group
Maternal and Child Health Centres (MCHC)	Developmental surveillance, initial screening, referral to CAS	0–5 years
Child Assessment Service (CAS), Department of Health	Comprehensive diagnostic assessment, post-diagnostic support, referral to intervention services	0–12 years
Early Education and Training Centres (EETCs)	Pre-school intervention (part-day programme)	2–6 years
Special Child Care Centres (SCCCs)	Full-day intensive pre-school programme for more severe cases	2–6 years
Integrated Programme in Kindergartens (IP/KG)	On-site support in mainstream kindergartens	3–6 years
Education Bureau (EDB) SEN support	Educational psychologist assessment, SEN support in mainstream schools, special school placement	School-age
Hospital Authority (HA) Child Psychiatry	Comorbidity management, medication, complex cases	All ages
NGOs (Heep Hong Society, Autism Partnership HK, SAHK, etc.)	Therapy services (ABA, SLT, OT), parent training, social groups	All ages
Social Welfare Department	Disability Allowance, respite care, supported employment, residential services	All ages

For completeness and exam awareness (not yet standard of care):

Therapy	Status	Concept
Oxytocin nasal spray	Investigational	Exploiting the role of oxytocin in social bonding; trials show inconsistent results for improving social cognition
Bumetanide (loop diuretic)	Investigational	Hypothesised to shift GABA from excitatory to inhibitory in immature neurons (correcting E/I imbalance); some positive trial results but not yet approved
Transcranial magnetic stimulation (TMS)	Investigational	Non-invasive brain stimulation targeting prefrontal/temporal regions; early-stage research
Microbiome-based therapies	Investigational	Based on gut-brain axis hypothesis; faecal microbiota transplant showed some promise in small trials
Digital therapeutics / AI-based interventions	Emerging	Wearable devices providing real-time social cue prompting; VR-based social skills training

High Yield Summary — Management of ASD

Goals: Foster acquisition of social, communicative, and cognitive skills → maximise functioning, independence, and QoL ^[2].

Approach: Individualised, based on strengths, difficulties, and developmental stage. Multidisciplinary team ^[2].

Non-pharmacological (ALWAYS first-line) ^[2]:

Behavioural: ABA/EIBI, behavioural modification, social skills training
Communication: Speech therapy, AAC (PECS, devices)
Educational: Special programmes (school-age), vocational training (older)
Family: Psychoeducation, parent training as co-therapist, counselling, genetic counselling
Other: Sensory therapy, CBT for anxiety, music therapy

Pharmacological (ADJUNCT — target symptoms, not core ASD) ^[2]:

Irritability/aggression: Risperidone or Aripiprazole (both FDA-approved)
ADHD symptoms: Methylphenidate, atomoxetine, guanfacine
Anxiety/depression/repetitive behaviours: SSRIs (fluoxetine, sertraline)
Sleep: Melatonin
Seizures: Standard AEDs

No medication cures ASD or treats core symptoms ^[2].

Prognosis: Core symptoms tend to improve over time; only minority achieve full independence; good prognostic factors = higher IQ, functional language by age 5, early intervention ^[2].

Active Recall - ASD Management

References

^[2] Senior notes: ryanho-psych.md (Section 12.2 Autistic Spectrum Disorder — Management, Prognosis)

Complications of Autistic Spectrum Disorder (ASD)

The complications of ASD are best understood not as "things that go wrong with ASD" in the way a myocardial infarction complicates coronary artery disease, but rather as the downstream consequences of living with a neurodevelopmental condition that impairs social communication and behavioural flexibility across the lifespan. They fall into several categories: psychiatric comorbidities, behavioural complications, neurological complications, physical health complications, psychosocial/functional complications, and family impact.

The key conceptual framework: ASD creates a cascading developmental trajectory — early social communication deficits → reduced social learning opportunities → impaired relationship formation → social isolation → psychiatric vulnerability → functional impairment → reduced independence. Each "complication" can be traced back to the core deficits through this chain.

1. Psychiatric Comorbidities

Psychiatric comorbidity is the rule, not the exception in ASD. Lifetime prevalence of at least one co-occurring psychiatric condition exceeds 70%. These are often the most treatable aspects of ASD and the greatest drivers of distress and functional impairment.

2. Behavioural Complications

3. Neurological Complications

Individuals with ASD have significant physical health disparities, partly due to communication barriers (can't report symptoms), behavioural barriers (can't cooperate with examinations), and systemic healthcare barriers (health services not adapted for ASD).

Complication	Prevalence	Why It Occurs
GI problems (constipation, GERD, abdominal pain)	~30-50%	Food selectivity → low-fibre diet → constipation. Serotonergic abnormalities affect GI motility (90% of body's serotonin is in the gut). Anxiety can exacerbate GI symptoms.
Feeding difficulties / Nutritional deficiency	Very common	Sensory-driven food selectivity → limited dietary variety → deficiencies in iron, zinc, calcium, vitamins. Obesity from restricted high-calorie diet.
Obesity	Increased	Food selectivity (often high-carb/processed foods), reduced physical activity (social sports difficult), medication side effects (risperidone, aripiprazole) ^[2].
Dental caries	Increased ^[2]	Oral sensory aversion → difficulty tolerating tooth-brushing. Food selectivity (sticky/sweet preferences). Difficulty cooperating with dental examinations.
Injuries	Increased	Impaired safety awareness (especially with ID), self-injurious behaviour, impulsive behaviour (if ADHD comorbid), sensory hyposensitivity to pain.
Premature mortality	2-3× population rate	Drowning (wandering + water fascination + reduced safety awareness), epilepsy-related death (SUDEP), accidents, suicide (especially in those without ID).

Mortality Risk in ASD

Studies consistently show that individuals with ASD have 2-3 times higher mortality than the general population. Leading causes include:

Epilepsy-related death (SUDEP, status epilepticus)
Drowning (wandering behaviour + water fascination + reduced safety awareness — this is a leading cause of death in young children with ASD)
Suicide (especially in ASD without intellectual disability — those with sufficient insight to recognise their social struggles but insufficient support)
Accidents/injuries
Medical complications related to co-occurring conditions

This underscores the importance of safety planning (water safety, wandering prevention, seizure management) and mental health monitoring.

5. Psychosocial and Functional Complications

These are often the most impactful complications from the patient's and family's perspective.

ASD does not only affect the individual — it profoundly impacts the entire family system ^[2]:

Domain	Impact	Why
Parental mental health	Higher rates of depression, anxiety, and chronic stress in parents of children with ASD	Grief at diagnosis, daily caregiving demands, sleep deprivation (child's sleep problems), behavioural challenges, navigating services, financial burden, social stigma
Marital/relationship strain	Higher divorce rates debated but relationship stress is well-documented	Disagreements about management, unequal caregiving burden, reduced couple time, grief process out of sync
Sibling impact	Siblings may experience neglect, parentification, embarrassment, or resilience/empathy	Parental attention directed to the child with ASD; sibling may also carry genetic risk for BAP or ASD
Financial burden	Substantial — therapy costs, reduced parental earning capacity, special schooling	ABA therapy alone can cost HK$500-1500+/hour; many therapies not covered by public health system
Social isolation of the family	Families may withdraw from social activities due to the child's behavioural difficulties or stigma	Public meltdowns, staring, judgement from others, difficulty arranging childcare

This is why family support, psychoeducation, counselling, and practical help ^[2] are not optional extras but essential components of ASD management.

Category	Key Complications	Pathophysiological Link
Psychiatric	Anxiety (~40-50%), ADHD (~30-50%), depression (~12-40%), OCD, eating disorders, psychosis	Shared neurobiology; secondary to social stress; serotonergic/dopaminergic dysfunction
Behavioural	SIB, aggression, soiling/enuresis, sleep disorders ^[2]	Communication frustration, sensory dysregulation, executive dysfunction, melatonin abnormalities
Neurological	Seizures (~25%), catatonia, motor deficits ^[2]	E/I imbalance, aberrant neurodevelopment, basal ganglia/frontal dysfunction
Physical	GI problems, feeding difficulties, obesity, dental caries, injuries, premature mortality	Sensory selectivity, medication effects, safety awareness deficits, communication barriers
Psychosocial	Social isolation, bullying, academic underachievement, unemployment, relationship difficulties, suicidality	Cascade from core social communication deficits
Family	Parental mental health, marital strain, sibling impact, financial burden	Chronic caregiving demands, grief, system navigation

High Yield Summary — Complications of ASD

Psychiatric comorbidity is the rule (> 70% lifetime): Anxiety is the most common (~40-50%), followed by ADHD (~30-50%) and depression (especially in adolescence) ^[2]. Always screen and treat comorbidities — they are often more treatable than core ASD.

Behavioural: Self-injurious behaviour, aggression, sleep disorders (~50-80%), soiling/enuresis ^[2]. Sudden behavioural change = rule out medical cause (pain, seizures, medication side effects).

Neurological: Seizures occur in ~25%, usually by adolescence ^[2], bimodal onset. Risk increases with ID and genetic syndromes. Catatonia in ~12-17% of adolescents/adults — must recognise and treat ^[2].

Physical: GI problems, feeding difficulties, obesity, dental caries, increased injury and premature mortality (2-3×). Drowning is a leading cause of death in young children with ASD.

Psychosocial: Social isolation, bullying (4× risk), academic underachievement, unemployment (50-80%), suicidality (elevated in ASD without ID). Only a minority achieve independence in adulthood ^[2].

Family impact: Parental depression/stress, financial burden, sibling effects. Family support is an essential part of management ^[2].

Key clinical pearl: The most modifiable complications are psychiatric comorbidities, sleep disturbance, and family support — prioritise these in management.

Active Recall - ASD Complications

References

^[2] Senior notes: ryanho-psych.md (Section 12.2 Autistic Spectrum Disorder — Clinical features, Other behavioural and neuropsychiatric problems, Prognosis, Management; Section on Intellectual Disability — Other problems in patients with ID)

High Yield Summary

Epidemiology: ~1% prevalence; M:F ≈ 4-5:1; high comorbidity with ID (~31%), ADHD, anxiety, epilepsy.

Aetiology: Heritability ~80-90%. Polygenic (common SNPs + rare CNVs). Environmental second hits (prematurity, valproate, paternal age). NOT caused by vaccines or parenting.

Pathophysiology: Aberrant synaptic pruning → altered connectivity (↓ long-range, ↑ local) → cognitive phenotype (impaired ToM, executive dysfunction, WCC) → behavioural phenotype.

Core Features — Domain A (Social Communication): Reduced reciprocity, poor nonverbal communication (eye contact, gestures, prosody), difficulty with relationships.

Core Features — Domain B (RRBs): Motor stereotypies, insistence on sameness, circumscribed interests, sensory hyper/hyposensitivity. Need ≥ 2 of 4.

Red Flags (Early): No babbling by 12mo, no gestures by 12mo, no words by 16mo, no 2-word phrases by 24mo, regression at any age, absent joint attention.

High Yield Summary — Differential Diagnosis of ASD

Core differentiating principle: ASD = social communication deficit (disproportionate to cognitive level) PLUS restricted/repetitive behaviours. Most mimics affect only one domain.

vs ID: Social skills match cognitive level in ID; disproportionately impaired in ASD. Can co-occur — need social communication below expected for developmental level.

vs Language Disorder: Nonverbal communication and social intent are NORMAL in language disorder. No RRBs. Imaginative play preserved.

vs Hearing Impairment: Normal social reciprocity, eye contact, imaginative play despite not hearing.

vs OCD: OCD rituals are ego-dystonic (distressing); ASD RRBs are ego-syntonic (comforting). Social/communication skills normal in OCD.

vs Social Anxiety: Child with social anxiety understands social cues but fears negative evaluation; child with ASD doesn't intuitively understand social cues.

Always screen for comorbidities — ADHD, anxiety, ID, epilepsy, genetic syndromes — because these are often more treatable than core ASD.

High Yield Summary — Diagnosis of ASD

ICD-10: 3 domains (social interaction + communication + RRBs), onset before age 3.

Gold standard instruments: ADOS-2 (observation) and ADI-R (parent interview). Screening: M-CHAT-R/F (toddlers 16-30 months).

No biomarker exists — ASD remains a clinical diagnosis based on expert judgement integrating history, observation, and standardised assessment.

High Yield Summary — Management of ASD

Goals: Foster acquisition of social, communicative, and cognitive skills → maximise functioning, independence, and QoL ^[2].

Approach: Individualised, based on strengths, difficulties, and developmental stage. Multidisciplinary team ^[2].

Non-pharmacological (ALWAYS first-line) ^[2]:

Behavioural: ABA/EIBI, behavioural modification, social skills training
Communication: Speech therapy, AAC (PECS, devices)
Educational: Special programmes (school-age), vocational training (older)
Family: Psychoeducation, parent training as co-therapist, counselling, genetic counselling
Other: Sensory therapy, CBT for anxiety, music therapy

Pharmacological (ADJUNCT — target symptoms, not core ASD) ^[2]:

Irritability/aggression: Risperidone or Aripiprazole (both FDA-approved)
ADHD symptoms: Methylphenidate, atomoxetine, guanfacine
Anxiety/depression/repetitive behaviours: SSRIs (fluoxetine, sertraline)
Sleep: Melatonin
Seizures: Standard AEDs

No medication cures ASD or treats core symptoms ^[2].

Prognosis: Core symptoms tend to improve over time; only minority achieve full independence; good prognostic factors = higher IQ, functional language by age 5, early intervention ^[2].

High Yield Summary — Complications of ASD

Behavioural: Self-injurious behaviour, aggression, sleep disorders (~50-80%), soiling/enuresis ^[2]. Sudden behavioural change = rule out medical cause (pain, seizures, medication side effects).

Physical: GI problems, feeding difficulties, obesity, dental caries, increased injury and premature mortality (2-3×). Drowning is a leading cause of death in young children with ASD.

Family impact: Parental depression/stress, financial burden, sibling effects. Family support is an essential part of management ^[2].

Key clinical pearl: The most modifiable complications are psychiatric comorbidities, sleep disturbance, and family support — prioritise these in management.

Autistic Spectrum Disorder

1. Definition

2. Epidemiology

2.1 Prevalence

2.2 Demographics

2.3 Comorbidities

3. Risk Factors

3.1 Genetic / Family History (Strongest Risk Factor)

3.2 Prenatal / Perinatal Factors

3.3 Environmental / Social Factors

3.4 What is NOT a Risk Factor

4. Anatomy and Functional Neuroanatomy

4.1 Brain Growth Trajectory

4.2 Structural Abnormalities

4.3 Connectivity Model

4.4 Neurochemistry

4.5 Mirror Neuron System

5. Etiology and Pathophysiology

5.1 Biological Factors

5.1.1 Genetics (The Dominant Aetiological Factor)

5.1.2 Neurobiological (covered in Section 4)

5.1.3 Immune / Inflammatory Factors

5.2 Psychological Factors (Cognitive Theories)

5.2.1 Theory of Mind (ToM) Deficit

5.2.2 Executive Function Theory

5.2.3 Weak Central Coherence (WCC) Theory

5.2.4 Enhanced Perceptual Functioning (EPF) Theory

5.2.5 Social Motivation Theory

5.3 Environmental / Social Factors

6. Classification

6.1 DSM-5 Classification (Current Standard)

6.2 ICD-10 Classification (Historical, Still Referenced in HK)

6.3 ICD-11 Classification (Current, from 2022)

7. Clinical Features

7.1 Domain A: Persistent Deficits in Social Communication and Social Interaction

7.1.1 Deficits in Social-Emotional Reciprocity

7.1.2 Deficits in Nonverbal Communication

7.1.3 Deficits in Developing, Maintaining, and Understanding Relationships

7.2 Domain B: Restricted, Repetitive Patterns of Behaviour, Interests, or Activities (RRBs)

7.2.1 Stereotyped or Repetitive Motor Movements, Use of Objects, or Speech

7.2.2 Insistence on Sameness, Inflexible Adherence to Routines, Ritualized Patterns

7.2.3 Highly Restricted, Fixated Interests Abnormal in Intensity or Focus

7.2.4 Hyper- or Hypo-reactivity to Sensory Input or Unusual Interest in Sensory Aspects of the Environment

7.3 Additional Clinical Features and Signs (Not Part of Core Diagnostic Criteria but Important)

7.3.1 Language and Communication

7.3.2 Play and Imagination

7.3.3 Motor Features

7.3.4 Cognitive Profile

7.3.5 Behavioural Features

7.4 Clinical Clues by Age Group

Preschool Children [2]

School-Age Children [2]

Adolescents [2]

7.5 Signs on Examination

8. Summary Table — Linking Pathophysiology to Clinical Features

Active Recall - ASD Definition, Epidemiology, Etiology and Clinical Features

References

Differential Diagnosis of Autistic Spectrum Disorder (ASD)

Guiding Principles for Differential Diagnosis

Differential Diagnosis Table

Differential Diagnosis — Clinical Decision Flowchart

Key Differentiating Concepts — Explained from First Principles

ASD vs Intellectual Disability: The "Proportionality" Question

ASD vs Language Disorder: The "Nonverbal Communication" Test

ASD vs ADHD: "Can't" vs "Won't" vs "Doesn't Know How"

ASD vs OCD: Ego-Syntonic vs Ego-Dystonic Repetitive Behaviours

ASD vs Schizophrenia: Developmental vs Episodic

ASD vs Social Anxiety Disorder: "Doesn't Understand" vs "Understands but Fears"

Conditions Commonly Co-occurring (Not Just Differential)

Summary — DDx at a Glance

Active Recall - Differential Diagnosis of ASD

References

Diagnostic Criteria

DSM-5 Diagnostic Criteria for Autism Spectrum Disorder (299.00)

DSM-5 Severity Specifiers

DSM-5 Additional Specifiers

ICD-10 Diagnostic Criteria for Childhood Autism (F84.0)

ICD-11 Diagnostic Criteria (6A02) — Current WHO System

Comparison of DSM-5 vs ICD-10 Criteria

Diagnostic Algorithm