9.7.1 Neurodevelopmental disorders

Autism spectrum disorder

Definition and classification

Autism spectrum disorder is defined by persistent difficulties in social communication and interaction together with restricted, repetitive behaviour, arising from highly heritable polygenic risk with some environmental contribution.

• The International Classification of Diseases, 11th revision (ICD-11), replaced the pervasive developmental disorder subtypes with one spectrum diagnosis.

• Diagnosis requires both domains, onset in the developmental period and clinically significant effects on functioning.

ICD-11

• Two domains each have their own listed manifestations: social communication and reciprocal interaction (including poor integration of speech with non-verbal cues), and restricted, repetitive, inflexible behaviour.

• No severity grade is given for autism itself, and ICD-11 uses qualifiers for intellectual development, functional language and loss of skills instead.

• A severity grade belongs only to a separately coded disorder of intellectual development.

• No fixed age of onset is set: onset lies in the developmental period, and features may become fully apparent only when social demands exceed capacity.

Developmental presentations and differential diagnosis

Tap to enlarge

Epidemiology

• Prevalence is about 1% worldwide (roughly 1 in 100) and 1 to 2% in UK studies.

• Sex ratio is about 3 boys to 1 girl (3 to 4:1), revised down from older clinic samples as under-recognition of autistic girls has been corrected.

• Autistic girls generally show less prominent restricted, repetitive interests and behaviours, as ICD-11 describes, and camouflaging can hide their needs.

Aetiology

Genetics

• Heritability is about 80 to 90%, making autism one of the most heritable psychiatric conditions, far above depression and anxiety.

• Monozygotic twin concordance is roughly 60 to 90%: high but below 100%, so the genetic contribution is strong but incomplete.

• Sibling recurrence is about 15% (10 to 20%), roughly ten times the population rate, on a multifactorial rather than Mendelian basis.

• Inherited genetic loading, shown by an affected sibling or twin concordance, is the strongest known risk factor, raising risk tenfold or more and outweighing every environmental factor.

• Fragile X syndrome is the commonest known single-gene cause, because it is relatively common and a large proportion of affected boys meet criteria for autism.

Environmental and perinatal factors

• Cerebellar pathology is associated with autism: vermal hypoplasia of lobules VI and VII on imaging, and reduced Purkinje cells at post-mortem.

Cognitive theories

Tap to enlarge

• Cognitive empathy, working out what another person thinks, is impaired in autism, while affective empathy, responding emotionally to their feelings, is relatively preserved.

Presentation and assessment

• Regression of words or social skills often happens between 15 and 24 months, and the National Institute for Health and Care Excellence (NICE) advises autism team referral for such regression before age 3.

• Diagnosis is usually possible in the preschool period, by about 4 years, although features may appear in infancy and milder cases are recognised later.

• Good eye contact, affection, pretend play or usual language milestones do not exclude autism.

• Hearing must be formally assessed first in a young child without spoken language, because deafness mimics autism; a passed newborn screen does not exclude later hearing loss.

• No structured tool, such as the Autism Diagnostic Observation Schedule, confirms or excludes autism on its own, and genetic tests are used on clinical indication rather than routinely.

Co-occurring conditions

Psychiatric

• Anxiety disorders are the most common co-occurring psychiatric condition, ahead of depression, disruptive behaviour, tics and psychosis.

• Attention deficit hyperactivity disorder is found in roughly 30 to 50% of clinical samples, more often than tics, conduct disorder, psychosis or obsessive-compulsive disorder, and both diagnoses can be made together.

• Without intellectual disability (formerly Asperger syndrome), anxiety and depression are the most frequent co-occurring conditions, well ahead of psychotic, bipolar, substance use and eating disorders.

Developmental and physical

• In epilepsy with autism, generalised tonic-clonic seizures predominate, and focal seizures with impaired awareness are less frequent.

Management

Principles

• Medication treats coexisting problems such as irritability, not the core social communication and repetitive behaviour features, and agents proposed for core features have failed in randomised trials.

• NICE advises against drugs, exclusion diets, secretin, chelation or hyperbaric oxygen for autism itself.

Psychosocial interventions

• Early behavioural intervention can substantially improve language, social, adaptive and cognitive skills, but restricted, repetitive behaviours, above all repetitive sensorimotor behaviours, change least.

• Social stories (Carol Gray) are individualised narratives that explain to a verbal autistic child what will happen in a specific upcoming situation and why.

Antipsychotics

• Risperidone and aripiprazole have the strongest randomised trial evidence for irritability, aggression and self-injury in autistic children and adolescents.

• They are a cautious, targeted, time-limited adjunct for severe behaviour, used once causes have been sought and behavioural approaches have failed or cannot be delivered.

• A paediatrician or psychiatrist names the target behaviour, reviews early at 3 to 4 weeks and stops at 6 weeks if there is no clinically important response.

• Prescribing either drug for irritability in autism is therefore off-label in the UK unless a separate licensed indication applies.

Antidepressants

• Antidepressant evidence for restricted and repetitive behaviours depends on age: placebo-controlled trials of selective serotonin reuptake inhibitors in autistic children are negative, with activation and more adverse effects.

• Small adult trials suggest modest benefit, and behavioural approaches come first.

Sleep

• Melatonin is the first-line medication for persistent sleep-onset insomnia in autistic children once a behavioural sleep plan has failed, backed by trial evidence, a UK licence and a circadian rationale.

• The licensed prolonged-release product covers ages 2 to 18, starting at 2 mg and increasing to 5 mg or 10 mg as needed.

Outcome

• Autism is lifelong, although abilities, presentation and support needs change, and some people later fall below the diagnostic threshold.

• Coexisting illness contributes to premature mortality, so depression, self-harm and suicidality should be assessed rather than put down to autism.

ADHD in children and adolescents

Definition and diagnostic criteria

Attention deficit hyperactivity disorder (ADHD) is developmentally excessive inattention, hyperactivity-impulsivity or both, causing impairment across settings.

• Language impairment is not one of the diagnostic criteria.

• ICD-11 requires several symptoms of inattention, hyperactivity-impulsivity or both, beyond expectations for age and intellectual development; difficulty waiting a turn is an impulsivity feature.

• Symptoms persist for at least six months, occur across multiple settings and impair functioning, with no better explanation; ICD-11 does not set a fixed numerical symptom threshold.

• Significant symptoms must have been present before age 12, although they may first come to clinical attention in adulthood.

Presentations and classification

ICD-11 uses three main presentations: predominantly inattentive, predominantly hyperactive-impulsive and combined.

The presentation reflects the currently predominant symptoms and may change over time.

Epidemiology

• ADHD is about four times commoner in boys in UK school-age community samples.

• Males predominate at every age, but the excess narrows from about 2:1 in children to about 1.6:1 in adults.

• The inattentive presentation is relatively commoner in girls, who may be missed until demands increase.

• The relative age effect means the youngest pupils in a school year are more likely to be diagnosed, so clinicians judge developmental maturity rather than comparing a child with older classmates.

Course and comorbidity

• Motor hyperactivity wanes earliest with maturation, while inattention and impulsivity persist longer. In adolescence, visible overactivity may become inner restlessness.

• About 40 to 50% still meet full diagnostic criteria as young adults, and many of the rest keep impairing subthreshold traits.

• Oppositional defiant disorder is the commonest coexisting psychiatric disorder, at roughly 30 to 50%.

• ADHD carries higher risks of educational failure, injury, substance use and offending. Registry studies link medicated periods with fewer accidents and convictions.

Aetiology

• Candidate genes such as DRD4 and DAT1 are not diagnostic tests.

• The prenatal smoking association is partly confounded by shared familial factors.

• The frontostriatal network is the circuit most consistently implicated: the lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate nucleus and putamen. Imaging shows underactivation during inhibitory control and attention tasks.

• The neurochemistry centres on dopamine and noradrenaline, including the locus coeruleus, in frontostriatal and prefrontal circuits, not on serotonin.

• No scan or cognitive profile establishes the diagnosis.

Tap to enlarge

Assessment and differential diagnosis

• A trained specialist makes the diagnosis from a full clinical, developmental and psychosocial assessment, using accounts from parents, school and the child.

• Rating scales such as the Conners, SNAP-IV and the Strengths and Difficulties Questionnaire support assessment and monitoring but cannot confirm or exclude ADHD.

• Before medication, the clinician records height, weight, pulse and blood pressure and takes a cardiovascular history. Cardiac symptoms or disease, a murmur, or sudden death in a first-degree relative under 40 need further assessment first.

Non-drug management

• Clinicians explain ADHD to the child, family and school and agree adjustments such as shorter tasks, less distraction, movement breaks and organisational support.

• In children under 5, the first-line treatment is an ADHD-focused group parent-training programme for parents or carers.

• Under 5, medication is advised against without a second opinion from a tertiary ADHD service, even after parent training.

• A child aged 5 or over with oppositional defiant or conduct disorder symptoms is offered a group parent-training programme before medication is escalated.

• The daily report card (school-home note) is a behavioural intervention: the teacher rates classroom behaviour against set goals and parents reinforce good reports at home.

• The advised diet is a balanced diet with good nutrition and exercise, not supplements such as fatty acids, additive elimination or removal of food groups.

• Cognitive behavioural therapy can help young people with continuing impairment who have benefited from medication.

Drug treatment sequence

The National Institute for Health and Care Excellence (NICE) guideline NG87 considers medication from age 5 when impairment persists after environmental changes have been made and reviewed.

• NICE judges each stimulant by a 6-week trial at an adequate dose before moving on.

• A once-morning modified-release methylphenidate solves a missed midday dose when the drug itself works; immediate-release forms act for about 2 to 4 hours.

• In adults, a stimulant (lisdexamfetamine or methylphenidate) is first line after environmental adjustments, with atomoxetine held in reserve.

Tap to enlarge

Tap to enlarge

• Stimulants are Class B, Schedule 2 controlled drugs in UK law, even in prodrug form, while non-stimulants are not.

• Effective ADHD drugs act on noradrenaline or dopamine, so a drug without that action has no trial evidence for core symptoms, whatever its evidence elsewhere.

• Pemoline, a stimulant, lost its UK licence and was withdrawn because of serious hepatotoxicity and acute liver failure.

• Modafinil was never licensed for ADHD, is not recommended under 18 and is linked to serious skin reactions including Stevens-Johnson syndrome.

Special situations

Adverse effects and monitoring

Stimulants

• Reduced appetite is the characteristic, very common adverse effect of stimulants, which is why growth is monitored. Meal timing, extra nutritious food and dietary advice help with weight loss.

• Prolonged continuous treatment can slow weight gain and slow height gain by about 1 cm a year early in treatment, and clinicians must raise this with parents.

• Height and weight are plotted on a growth chart at each review, routinely every six months, and a fall across centiles is an early sign.

• A planned break over the school holidays allows catch-up growth when height gain has slowed, at the cost of symptoms returning. Clinicians do not promise a fixed effect on final height.

• Methylphenidate can unmask or worsen motor and vocal tics by raising synaptic dopamine.

• Sleep problems are managed by changing dose timing or preparation and by looking for other causes.

• Clinicians review secure storage and diversion, especially in adolescence, because prolonged-release forms do not eliminate misuse.

Cardiovascular checks

• Pulse and blood pressure are checked before and after each dose change and every six months.

• Blood pressure persistently above the 95th centile needs paediatric hypertension assessment.

• A routine ECG is unnecessary before stimulants, atomoxetine or guanfacine unless cardiac features or another cardiac-risk medicine indicate one.

Non-stimulants and other drugs

Outcome and transition

• In the MTA trial, medication management and combined treatment were superior for core symptoms at 14 months. Groups later converged as actual treatment drifted from randomisation, which does not prove continued medication ineffective.

• Medication is reviewed at least annually, with supervised reduction or stopping considered when appropriate.

• The Driver and Vehicle Licensing Agency is notified when ADHD or its medication affects safe driving.

• Transfer to adult services is planned around school-leaving age, usually by 18, with the adult prescriber identified early.