Neurodevelopmental & Childhood-Onset Psychiatric Disorders

ADHD: diagnosis and neurobiology

Criteria. Attention-deficit/hyperactivity disorder is a persistent pattern of inattention and/or hyperactivity-impulsivity. A child needs at least 6 symptoms in a domain (at least 5 from age 17), lasting at least 6 months, with several symptoms present before age 12 and clear impairment in at least two settings such as home, school, or work. The presentation is labeled predominantly inattentive, predominantly hyperactive-impulsive, or combined.

Trouble confined to one setting (one classroom, one parent) does not meet ADHD criteria and should prompt a search for a situational, learning, or family cause.

Neurobiology and course. ADHD reflects underactive dopamine and norepinephrine signaling in prefrontal–striatal circuits that control attention, planning, and inhibition; imaging shows smaller, later-maturing frontal cortex. Heritability is about 75%. Hyperactivity tends to fade with age, whereas inattention often persists into adulthood.

ADHD pharmacology

Stimulants. Methylphenidate blocks the dopamine (DAT) and norepinephrine (NET) reuptake transporters; amphetamines also reverse the transporters and VMAT2, releasing dopamine and norepinephrine. Stimulants are first-line from age 6 alongside behavioral therapy (at ages 4–5, parent behavior training comes first) and are Schedule II drugs with misuse potential.

Nonstimulants. Atomoxetine (selective NET inhibitor) and the α2A agonists guanfacine and clonidine, which strengthen prefrontal signaling, have no abuse potential. They suit patients with substance-misuse risk, stimulant intolerance, or comorbid tics.

Autism spectrum disorder and Rett syndrome

Core features. Autism spectrum disorder (ASD) combines persistent deficits in social communication and interaction (poor eye contact, absent joint attention, limited back-and-forth reciprocity, difficulty forming relationships) with restricted, repetitive patterns of behavior (motor stereotypies such as hand-flapping, insistence on sameness, narrow intense interests, and over- or under-reactivity to sensory input), beginning in early development. Boys outnumber girls about 4:1. All toddlers are screened at 18 and 24 months (M-CHAT); vaccines do not cause autism.

Associations. Many children show accelerated early head growth (macrocephaly). About one-third have intellectual disability and roughly 20–30% develop epilepsy. Fragile X syndrome is the most common single-gene cause; tuberous sclerosis is another classic association. ASD is highly heritable, and advanced parental age raises risk.

Management. The foundation is early, intensive behavioral intervention (applied behavior analysis) with speech-language and occupational therapy. Risperidone and aripiprazole, both D2/5-HT2A–active antipsychotics, are FDA-approved for irritability and aggression associated with autism. No medication improves the core social deficits.

Rett syndrome. Rett syndrome is an X-linked dominant disorder caused by a (usually de novo) MECP2 mutation; MECP2 encodes methyl-CpG-binding protein 2, a regulator of gene expression in mature neurons. It affects almost only girls because hemizygous males typically do not survive. Development looks normal for about 6 months and stagnates at 6–18 months as head growth slows; regression follows at 1–4 years, with loss of speech and purposeful hand use, stereotyped hand-wringing, acquired microcephaly, ataxic gait, and irregular breathing (hyperventilation alternating with breath-holding). Seizures and scoliosis follow in later childhood.

Regression after normal early milestones in a girl, with hand-wringing and a falling head-circumference curve, is Rett until proven otherwise.

Intellectual disability

Definition. Intellectual disability requires deficits in intellectual functioning (IQ about 70 or below, roughly two standard deviations below the population mean of 100) and in adaptive functioning across conceptual, social, and practical domains, with onset during the developmental period. DSM-5 grades severity from mild to profound by adaptive functioning rather than IQ alone. Mild disability accounts for about 85% of cases.

Causes. Down syndrome (trisomy 21, usually sporadic maternal nondisjunction) is the most common genetic cause. Fragile X syndrome is the most common inherited cause: a CGG trinucleotide expansion of more than 200 repeats in FMR1 triggers hypermethylation that silences the gene. Affected boys have a long face, large jaw, large everted ears, hypermobile joints, mitral valve prolapse, autistic features, and macroorchidism after puberty. Fetal alcohol syndrome is the leading preventable cause. Other causes include untreated phenylketonuria, congenital hypothyroidism, congenital (TORCH) infections, and lead exposure.

Tic disorders and Tourette syndrome

Tics. Tics are sudden, rapid, recurrent, nonrhythmic movements or vocalizations that wax and wane, can be briefly suppressed, and follow a premonitory urge. All tic disorders begin before age 18.

• Tourette syndrome: multiple motor tics plus at least one vocal tic, not necessarily at the same time, for more than 1 year.
• Persistent (chronic) motor or vocal tic disorder: motor tics or vocal tics, but not both, for more than 1 year.
• Provisional tic disorder: tics present for less than 1 year.

Comorbidity and treatment. Coprolalia is uncommon (about 10–15%). Most patients have ADHD and/or OCD, often more impairing than the tics. Treatment starts with education and habit-reversal training (CBIT). If tics remain impairing, α2 agonists (guanfacine, clonidine) come next and also treat coexisting ADHD; antipsychotics (aripiprazole, haloperidol, pimozide) are the most potent tic suppressants but carry extrapyramidal risk, and pimozide prolongs the QT interval (baseline ECG).

Disruptive and elimination disorders

Oppositional defiant disorder (ODD). At least 6 months of angry or irritable mood, argumentative and defiant behavior, and vindictiveness, directed mainly at authority figures such as parents and teachers. Serious violations of other people's rights are absent. Some children progress to conduct disorder.

Conduct disorder. A repetitive pattern of violating others' basic rights or major social norms, with at least 3 qualifying behaviors in 12 months: aggression toward people or animals, destruction of property (including fire-setting), deceitfulness or theft, and serious rule violations (truancy, running away). From age 18, if conduct disorder was evident before 15, the diagnosis becomes antisocial personality disorder. Treatment is psychosocial (parent-management training, multisystemic therapy).

Disruptive mood dysregulation disorder (DMDD). Severe temper outbursts at least 3 times a week, grossly out of proportion to the trigger, with persistently irritable mood between them, for at least 12 months in at least two settings. Onset is before age 10, and the diagnosis is made only between ages 6 and 18. DMDD was introduced to curb overdiagnosis of pediatric bipolar disorder; these children tend to develop depression or anxiety, not mania.

Enuresis. Repeated voiding into the bed or clothes at least twice a week for at least 3 months in a child aged 5 or older. Primary nocturnal enuresis is most common and strongly familial, reflecting maturational delay. The bed-wetting alarm gives the most durable cure; desmopressin, an ADH analog acting on collecting-duct V2 receptors, works quickly but relapse is common when it stops. Imipramine is a rarely used third-line option.

Encopresis. Repeated passage of stool in inappropriate places in a child aged 4 or older, usually from chronic constipation with overflow incontinence. Treatment is disimpaction, maintenance laxatives, and scheduled toileting.