Autism Spectrum Disorder and ADHD — DSM-5 Criteria, Screening, Aetiology and Treatment

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder. In DSM-5 (2013) one spectrum replaced the older DSM-IV categories of autistic disorder, Asperger disorder and pervasive developmental disorder not otherwise specified; Rett syndrome and childhood disintegrative disorder were no longer folded into it. ASD is now defined by one set of criteria in two domains: social communication deficits and restricted, repetitive behaviours.

Attention deficit hyperactivity disorder (ADHD) is a condition of developmentally inappropriate inattention, hyperactivity or impulsivity that starts early and interferes with daily life. It is considered a dysfunction of executive function, mainly a frontal-lobe activity, so patients struggle with decision making and emotional regulation as well as attention. Both disorders begin in childhood, both are diagnosed clinically with no laboratory or imaging test, and both are heritable — which is why they are tested together under neurodevelopmental disorders.

DSM-5-TR uses specifiers: current severity, with or without intellectual impairment, with or without language impairment, association with a known genetic or medical condition or environmental factor, and catatonia. DSM-5 therefore describes two domains (social communication; restricted, repetitive behaviour) — a classic exam trap when older books list more.

The American Academy of Pediatrics recommends screening all children for ASD, because early intervention may improve outcomes; its 2020 clinical report advises standardised screening at 18 and 24 months with ongoing developmental surveillance, and notes that ASD can be diagnosed as young as 18 months. Early red flags are:

• Not responding to their name by 12 months.
• Not pointing at objects to show interest by 14 months.
• Not pretend-playing by 18 months.
• Avoiding eye contact, delayed speech, repeating words or phrases, getting upset by minor changes, obsessive interests, repetitive movements and unusual reactions to sensory stimuli.

There is no laboratory test or imaging study for ASD. The evaluation includes a full developmental, medical, social and family history (prematurity, teratogen exposure, family history of developmental problems), a complete physical and neurological examination for dysmorphic features or neurocutaneous skin signs, hearing and vision tests, and structured behavioural observation. Parent questionnaires such as the Social Communication Questionnaire or Social Responsiveness Scale structure the history; the Autism Diagnostic Interview-Revised is a long parent interview used in research settings. The two validated observation tools that give structured data to confirm the diagnosis are the ADOS-2 (Autism Diagnostic Observation Schedule, Second Edition) and the Childhood Autism Rating Scale, Second Edition; ADOS-2 requires specialist training.

ASD is most likely caused by an interplay between genetic predisposition and environmental factors. Concordance is high in monozygotic twins, siblings and families, with heritability estimated at about 50%. The aetiology is multigenic and heterogeneous — hundreds of risk genes are known, and people with similar variants can have very different phenotypes. Neurobiological hypotheses include impaired neural connectivity and synaptogenesis, excitation–inhibition imbalance and neuroinflammation; the pathophysiology is still elusive.

• Prenatal associations — maternal rubella, influenza or cytomegalovirus infection, fever in pregnancy, gestational diabetes, maternal obesity, advanced parental age, assisted reproductive technologies, and exposure to valproic acid or other antiepileptic drugs.
• Vaccines do not cause autism. Robust studies found no link with thimerosal, mercury or the MMR vaccine.
• Prevalence varies with diagnostic methods. A global meta-analysis gave pooled estimates of about 1.01% in North America, 0.73% in Europe and 0.41% in Asia.

Management is individualised and multidisciplinary. The evidence base classifies focused intervention practices (for example discrete trial training, antecedent-based interventions, differential reinforcement, augmentative and alternative communication, social-skills training) and comprehensive programme models. Core elements of effective programmes are early assessment, goal setting, trained clinicians, a structured learning environment, behavioural management, family support and planned transitions.

Drugs treat target symptoms and comorbidities, not the core social deficit, and are used as part of a comprehensive plan after risks and benefits are weighed and consent is obtained. The prognosis varies: in one report 9 in 10 children diagnosed before 6 years still met criteria a year or more later. Favourable factors are higher cognitive skills at 2 years, early intervention, fewer repetitive behaviours, higher verbal IQ and family and community support.

In children, ADHD is diagnosed when there is difficulty with at least 6 of the 9 symptoms in the inattentive or the hyperactive-impulsive list (DSM-5). Symptoms must have started before age 12, lasted at least six months, be present in more than one setting (home, school, after-school activities) and cause significant impairment, without being better explained by another disorder.

• Male-to-female ratio about 2:1; prevalent in about 3–6% of adults.
• Highly heritable — greater concordance in monozygotic than dizygotic twins; siblings have about twice the general-population risk.
• Other risk factors explored: smoking in pregnancy, fetal alcohol exposure, nutritional deficiency and viral infections.
• No diet has been shown to improve ADHD. Rating scales (for children the Vanderbilt ADHD scale, which has parent and teacher components; the Brown ADD scale in adults) from multiple informants support the history.

There are no consistent findings on routine brain imaging. Research points to small anterior cingulate gyrus and dorsolateral prefrontal cortex and reduced frontostriatal activity on functional MRI, which are thought to account for deficits in goal-directed behaviour. Dopaminergic receptor numbers and noradrenergic receptor involvement have both been implicated. This is the rationale for drugs that raise dopamine and noradrenaline.

Pharmacotherapy is the mainstay, divided into stimulants and non-stimulants. Stimulants — methylphenidate and amphetamines — block dopamine reuptake at presynaptic and postsynaptic membranes; amphetamines also release dopamine directly. They are effective in about 70% of patients with a number needed to treat of about 2. Side effects include blood pressure changes, reduced appetite, sleep disturbance and risk of dependency; treating ADHD with stimulants reduces the lifetime risk of substance misuse despite the controlled status of the drugs.

Psychosocial treatment — psycho-education for family and patient and cognitive-behavioural training programmes — works best combined with medication. Differential diagnosis includes mood and anxiety disorders, substance misuse, hearing, learning and other developmental disorders; patients with hypertension may avoid stimulants.

• Red flag at 12/14/18 months (name, pointing, pretend play) → ASD.
• Core DSM-5 change → one spectrum; no Asperger or PDD-NOS.
• First-line drug in ADHD → methylphenidate or amphetamine; non-stimulant → atomoxetine.
• ADHD subtype most common → combined (about 70%).
• Vaccines and autism → no association.