Autisme

01Pathophysiology

Childhood autism is a pervasive developmental disorder rooted in atypical neurodevelopment that begins during prenatal brain formation and manifests behaviorally in early childhood. The PPDGJ-III emphasizes that abnormalities must be present before the age of 3 years, reflecting the early-onset nature of this condition.

The underlying mechanism involves disrupted neural connectivity. During normal brain development, neurons form organized networks that support social cognition, language processing, and behavioral flexibility. In autism, there is evidence of both local over-connectivity (excessive short-range synaptic connections within brain regions) and long-range under-connectivity (deficient communication between distant brain areas such as the prefrontal cortex and posterior temporal regions). This imbalance helps explain why children with autism may excel in detail-oriented tasks but struggle with integrating complex social information.

The mirror neuron system, which underpins the ability to imitate others and understand their intentions, shows functional differences in autism. This directly explains the PPDGJ-III criterion of impaired social imitative play and the difficulty in reading non-verbal cues. When vignettes describe a child who "does not imitate waving bye-bye" or "does not engage in pretend play," they are testing your understanding of this mechanism.

The amygdala and its connections to the fusiform face area are also implicated. Early amygdala overgrowth followed by arrested development contributes to impaired face processing and emotional recognition, which maps directly to the PPDGJ-III description of "inadequate appreciation of socio-emotional cues" and "lack of emotional response to others' verbal and non-verbal expressions."

Repetitive and stereotyped behaviors are linked to basal ganglia and corticostriatal circuit dysfunction, resulting in an overreliance on habitual motor programs and difficulty shifting between behavioral sets. This explains the "insistence on sameness" and distress when routines are disrupted.

Genetic factors play a substantial role, with heritability estimates exceeding 80%. However, no single gene is responsible. Hundreds of genes are implicated, many converging on pathways involved in synaptic formation, chromatin remodeling, and transcriptional regulation (e.g., SHANK3, CHD8, MECP2). Environmental modifiers such as prenatal valproate exposure and advanced paternal age act on these vulnerable genetic backgrounds.

Importantly, approximately three-quarters of children with childhood autism also have intellectual disability (mental retardation), as noted explicitly in the PPDGJ-III. However, all IQ levels can be found, and the presence of normal or high IQ does not exclude the diagnosis.

02Classification and Clinical Manifestation

The PPDGJ-III organizes the clinical features of childhood autism into three core domains, often referred to as the "triad of impairments."

Triad of Impairments

Severity and Associated Features

03Diagnostic Workup

The diagnosis of childhood autism under the PPDGJ-III is fundamentally clinical. There is no laboratory test, biomarker, or imaging study that confirms the diagnosis. The diagnostic process relies on a combination of detailed developmental history, direct behavioral observation, and exclusion of other conditions.

The best initial step when a parent raises concern about a toddler's social or communicative development is to administer the M-CHAT-R/F (Modified Checklist for Autism in Toddlers, Revised with Follow-Up). This is a parent-completed screening questionnaire designed for children between 16 and 30 months. It is not diagnostic but stratifies risk and identifies children who need formal evaluation.

The most accurate test for confirming the diagnosis is a comprehensive evaluation that includes the ADOS-2 (a clinician-administered, semi-structured observational assessment) and the ADI-R (a structured caregiver interview). The ADOS-2 is considered the gold standard observational instrument. It uses standardized "presses" for social interaction, communication, play, and repetitive behaviors to generate a diagnostic algorithm score.

A critical part of the workup is audiometry or auditory brainstem response (ABR) testing to rule out hearing impairment as a cause of language delay. This step is frequently tested: if a child presents with language delay, you must exclude hearing loss before attributing symptoms to autism.

Developmental and IQ testing should be performed in all cases, given the high rate of comorbid intellectual disability emphasized in the PPDGJ-III (approximately 75%). The result also guides educational and intervention planning.

Genetic testing (chromosomal microarray and Fragile X DNA testing) is recommended as part of the etiologic workup but does not confirm or exclude autism. Routine neuroimaging and EEG are not indicated unless there are additional clinical concerns (seizures, regression, focal neurological findings, or significant macrocephaly).

04Management and Treatment

The cornerstone of autism management is early, intensive behavioral intervention, not pharmacotherapy. The single most testable principle is that Applied Behavior Analysis (ABA) is the best-studied and most strongly recommended intervention, particularly when initiated before age 4 and delivered at high intensity (25-40 hours per week). ABA uses structured, repetitive learning trials with reinforcement to build social, communicative, and adaptive behaviors while reducing harmful or disruptive ones.

Speech-language therapy is essential for nearly all children with autism, addressing not just expressive and receptive language but also pragmatic communication (turn-taking, topic maintenance, understanding indirect language). For nonverbal children, the introduction of augmentative and alternative communication (AAC) systems, such as picture exchange systems (PECS) or speech-generating devices, is a priority. A common exam trap is assuming that AAC discourages spoken language development; it does not, and in fact often facilitates it.

Occupational therapy addresses sensory processing challenges, fine motor skills, and activities of daily living. Many children with autism have either hypersensitivity (covering ears in noisy environments) or hyposensitivity (seeking deep pressure) to sensory input.

Pharmacotherapy is strictly adjunctive and symptom-targeted. No medication treats the core features of autism (social impairment, communication deficits). The two FDA-approved medications for irritability/aggression/self-injury associated with autism are:

1. Risperidone (approved for age 5 and above): Initial dose 0.25 mg/day for children under 20 kg, 0.5 mg/day for those 20 kg or above. Titrate gradually over 2 weeks to an effective dose (typically 0.5-3 mg/day). Monitor weight, fasting glucose, lipid panel, and prolactin levels.

2. Aripiprazole (approved for age 6 and above): Initial dose 2 mg/day, titrated to 5-15 mg/day. Lower risk of weight gain and metabolic effects compared to risperidone, but akathisia (restlessness) is a notable side effect.

Melatonin is first-line for the very common comorbidity of sleep-onset insomnia, dosed at 0.5-5 mg given 30-60 minutes before the desired bedtime.

There is no role for chelation therapy, secretin, hyperbaric oxygen, or restrictive diets (e.g., gluten-free/casein-free) as evidence-based treatments. Questions that offer these as answer choices are testing your ability to identify unproven interventions.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students lose points on autism questions is by confusing language delay with autism or by selecting a diagnostic test when the answer is clinical observation. A vignette describing a 2-year-old who does not speak yet but points, makes eye contact, and plays peek-a-boo is not autism. The child has preserved social reciprocity and nonverbal communication, pointing instead toward isolated language delay or hearing impairment. Always look for the social dimension: the absence of joint attention, social smile, and emotional reciprocity is what separates autism from other causes of language delay.

A second common trap involves the age criterion. The PPDGJ-III states that symptoms must appear before age 3. If a vignette describes a child who developed completely normally until age 4 and then lost skills, think Childhood Disintegrative Disorder, not childhood autism. Similarly, if there is normal early language and cognitive development with isolated social oddity, think Asperger Syndrome.

Students also frequently err by selecting MRI or EEG as the diagnostic test. These are not routine and are not confirmatory for autism. The diagnosis is clinical. Audiometry, however, should always be performed to exclude hearing loss, and this is a commonly tested "next best step" when a child presents with language delay.

On the treatment side, the trap is selecting a medication as first-line therapy. No medication treats the core symptoms of autism. The best initial intervention is always behavioral (ABA), and pharmacotherapy is reserved for comorbid symptoms like irritability, aggression, or insomnia. If a vignette describes a child with autism who is aggressive and self-injurious despite behavioral interventions, the next step is risperidone or aripiprazole, not an SSRI or stimulant.

Finally, remember the IQ pearl from the PPDGJ-III: approximately 75% of children with childhood autism have comorbid intellectual disability, but all IQ levels can occur. A vignette of a child with autism and a normal IQ does not rule out the diagnosis, and this is a frequent distractor designed to make you second-guess yourself.