Module 3 - Childhood disorders (perinatal mental health, ADHD, conduct, autism, learning disabilities, eating disorders, PTSD) Flashcards
What is the definition of ADHD?
Inattention + Hyperactivity + Impulsivity, >6 months, pervasive, <7 years, significant impairment.
6+: Fails to sustain attention, follow-thru on instructions/work, listen, Careless errors, Avoids tasks requiring mental effort, Loses things, Easily distracted
Forgetting, Poor planning (esp. adolescents/adults)
3+: Fidgets or squirms, Leaves seat, Excess running about, Unduly noisy, Excess motor activity
1+: Blurts out answers, Fails to wait in lines / their turn
Interrupts or intrudes others, Excess talking
Co-morbidities: Conduct disorder (25-50%)
Anxiety disorder (25%) / Depressive disorder (15%)
Learning difficulties (30%), Including specific reading difficulties
Tourette’s disorder
Alcohol and substance misuse
Offending (45% young adults in prison have hyperactivity)
The symptoms of ADHD cause spiralling as people socially isolate themselves which means they are more likely to become rejected in the future and become delinquents and then isolate more, etc.
What is the epidemiology of ADHD and how do the RFs relate to pathology and function?
1% hyperkinetic disorder (narrow definition ICD10)
5% ADHD (broad definition DSM-IV)
M:F 3:1
Inner City / Low SES / Institutions
Maternal smoking (OR~2) - Dose-response
Maternal alcohol and subs misuse, Maternal stress
ADHD ~ Pregnancy/birth Cx
v. low birthweight (OR~2)
Environmental lead, organophosphates, PCBs
Nutritional deficiencies (zinc, mg) & surpluses (sugar, food additives) (– correlation, but not proven risk factor, not in NICE guidelines)
More critical comments, less encouragement, Poor coping, less sensitivity to child’s needs, Inconsistency / disagreement in parenting, Maltreatment / physical discipline, Maternal depression (possibly ~ above factors)
Romanian orphanages showed more inattention / overactivity (i/o) in 6yr olds: 30% Romanians adopted in UK at 2yr+ had sig i/o compared to 10% Romanians adopted in UK <6mo…(shows causality) and 10% UK adoptees…
But no differences re oppositional / conduct difficulties
Attachment? Lack of carer availability → child fails to draw security from predicted carer presence → disrupted development of such regulation capacity →
later impulsivity
ADHD often do poorly on executive function tests, eg. stroop, Wisconsin card sorting test. poor planning/working memory - fits in with reduced activity on fMRI during EF tasks
8x increased risk of child ADHD if parent meets ADHD criteria
Heritability (proportion of variance due to genetic differences between individuals) ~ 0.66 but no study revealed a gene variant passing stats threshold… ?due to small study samples (max 3000 cf 10,000’s cases)
DRD4 and DAT1 mainly but also:
Tyrosine hydroxylase?, DRD 2, 3, 5
COMT, especially val/val158met (↑ breakdown DA) ~ anti-social (only in ADHD) (reduced executive function too)
DA-beta-hydroxylase (DA → NA)
5HT may also modulate DA transmission
SNAP-25 (axonal growth)?
Neumann 2007 - DRD4 and DAT1 high risk alleles + smoking (OR = 9 compared to ~1 for just genetic or just environmental risk factors)
Reduced size of prefrontal cortex, reduced CBF in SPECT and reduced white matter seen, but also in siblings/parents without ADHD.
BUT maybe it’s problem with down-top instead of top-down - posterior parietal cortex signals to prefrontal cortex which stimuli to prioritise and there’s less CBF in ADHD
Also reduced blood flow and cortical volume in basal ganglia and cerebellum, areas of the brain which signal to prefrontal cortex predictions of events and therefore irregularities (DA in both…)
What is the management of ADHD?
Assessment
Hx (parents / child / school) inc comorbidity
Scales – Connors
Cognitive, ? Hearing
Psycho-education - enforce rules consistently, more praise
2nd line: ‘Stimulants’
Methylphenidate (MPH) / Dexamfetamine
Competitive blocker of DAT
Agonist on post-synaptic receptors eg. D4R
MPH clears striatum in 90min and oral gives slower kinetics so not abused?
SEs: Reduced appetite / weight / growth
Need regular height & weight checks, Sleep, Tics, Mood
Atomoxetine - NA reuptake inhibitor
Usually given if subs abuse, treatment-resistance
90% Conduct Disorder if untreated
As adults (1/3 continue to meet diagnosis)
Hyperactivity & impulsivity decreases with age
but inattention, restlessness, disorganisation…
25% anti-social personality (2° conduct disorder?)
Increased Substance misuse (2° conduct disorder?)
What is the definition of autism?
Impaired communication + impaired social interactions + restricted, repetitive, stereotypical behaviours, abnormal developmental age for chronological age
75% of individuals with autism have IQ levels < 70.
Boys-girls 4-1, before 3yo
Autistic ‘savants’ – extraordinary skills not exhibited by most persons are rare
Subgroups: Autism, Asperger’s Syndrome (Similar features to autism with impaired communication and reciprocal interaction, BUT no general delay or retardation in language or in cognitive development
Most normal IQ, boys, clumsy), Pervasive Developmental Disorder-NOS, Atypical Autism, Disintegrative Disorder
Impaired communication: Speech delay, Stereotyped and repetitive speech (eg. echolalia, idiosyncratic use of words etc.), Lack of social usage of language, Poor gesture (eg. pointing to express interest, instrumental gestures), Lack of varied spontaneous make-believe and creative play
Social interaction: Impaired reciprocal interaction, Miss social-emotional cues and lack reciprocity, Lacking ‘Theory of mind’, Literal, concrete understanding, Failure to develop peer relationships, Lack of shared enjoyment and pleasure
Behaviours: Tendency not to use objects in intended functional fashion (i.e. repetitive use, unusual sensory interests), Little imaginative play, Stereotyped motor mannerisms (i.e. hand and finger/complex mannerisms, Adherence to non functional routines/rituals
At an early age: Feeding problems, Dislike of physical contact/content to be alone ‘angel baby’, Not lifting arms to be lifted, Not snuggling down when held, Fascination with lights, spinning, TV, music, etc., Lack of curiosity, Lack of social pointing and eye contact, Motor milestones may be delayed, Babbling limited in quantity and quality
Early involvement of: Paediatrician/child psychiatrist, speech therapist, clinical/educational psychologist, vision and hearing tests, language tests (receptive-expressive language disorder instead autism? Whereas the vision and hearing problems cause developmental delay but also higher rates of autism among children with hearing and vision problems because neurological problem causes both. Romanian orphan level of deprivation?
What is the epidemiology and RFs of ASD?
Chakrabarti and Frombonne 2006: Autism 25 per 10,000, Total ASD 116/10,000
Twin studies show concordance rates in MZ twins of between 36-60%
If 2 children affected risk rises to ~25%
Personality traits in family members, rates engineers children, ‘exotic’ immigrant mothers
Past studies predicted 3-5 genes involved (now ~10?, 20 out 23 chromosomes implicated)
Medical Conditions – causative 6-10% - Tuberose Sclerosis, Fragile X, Maternal Rubella, Herpes Simplex Encephalitis (can occur at any age), Neurofibromatosis, untreated Phenylketonuria, Blindness/Deafness, Chromosomal abnormalities e.g. Downs, Turners
Increased rates of affective disorder in family members which pre-dates ASD diagnosis
Increased rates of anorexia nervosa
Traumatic birth (possibly due to neurologically compromised baby) Diet?, Pollutants, Antibiotics, Allergies, Traces of neurotoxins in preservatives, Severe deprivation
20% of ASD have non-febrile seizures under age of 3
15-20% develop seizures during adolescence
Any type of fit can be seen
Rates of abnormal EEG’s are high
What investigations can be done for autism?
Bloods TORCH screen for prenatal infections Toxoplasma Rubella Cytomegalo virus Herpes simplex Chromosomal karyotyping CT or MRI
Mainly: Clinical assessment including full history from infancy until present by multidisciplinary ‘autism team’
Consultant child psychiatrist/paediatrician,
Educational/clinical psychologist
Speech and language therapist
Child observation
Psychometric testing
ADOS-2 Autism Diagnostic Observation Schedule
ADI-R Autism Diagnostic Interview-Revised
DISCO (Wing and Gould)
Diagnostic Interview for Social and Communication Disorders
3di (Skuse)
The Developmental, Dimensional and Diagnostic Interview
CHecklist for Autism in Toddlers (CHAT) screening (very specific but not very sensitive)
Social and Communication Disorder Checklist SCDC (Skuse 2005) 8-24 points suggests ASD
What is the management for ASD?
No known cure
Appropriate educational placement is hardest to achieve but most effective
PACT trial showed observed play and feedback from therapists reduced symptom severity at 6 month FU
Speech and language therapy, especially early and intensive, Macaton (for nonverbal children)
Medication;- risperidone, clomipramine, fluvoxamine, stimulants for comorbid ADHD (30%)
Occupational therapy for dyspraxia
Special needs education placement
Reduce unwanted behaviours and reinforce desired behaviours
Reduce impact of obsessional behaviours
Reduce destructive and aggressive behaviours
SPELL-NAS schools (few places), LOVAAS (costs £20,000), schools usually only provide few hours a week with a specialist teacher in mainstream school in a class of 30
Early symptoms tend to disappear with age , 15% symptom free as adult
Severe social/communication impairments tend to remain and the overall outlook for most autistic children is poor
Some studies have shown autistic children living independent lives and long term relationships in adulthood
Bad prognostic factors:
Regression,
Low IQ
No speech by 7 years of age, and unlikely ever to talk
What is intelligence and intellectual disability?
The mental abilities necessary for adaptation to, as well as selection and shaping of, any environmental context. According to this definition, although the behaviour that is labelled as intelligent may differ from one environmental context to another, the mental processes underlying this behaviour do not (Sternberg, 1997).
[Intelligence] . . . involves the ability to reason, plan, solve problems, think abstractly, comprehend complex ideas, learn quickly and learn from experience. It is not merely book learning, a narrow academic skill, or test-taking smarts. Rather it reflects a broader and deeper capability for comprehending our surroundings—“catching on,” “making sense” of things, or “figuring out” what to do. (p. 13)
(Linda Gottfredson1997)
Spearman (1927): Proposed intelligence composed of:
general factor (g) (high correlations >0.9)
Specific factors (s)
Salthouse 2004: g = reasoning, memory, spatial ability, vocabulary, processing speed* *= affected by age
Sternberg Triarchic Theory: Assess
Information processing skills
- encode, combine, compare information
Experience
- past exposure & practice, learning with repetition
Context
-intelligence manifest in situations
Successful intelligence requires three abilities:
Analytical abilities: those taught in schools, reasoning
Creative abilities: news ways of addressing issues & concerns
Practical abilities: used in everyday situations: work , social/professional interactions etc; mostly not taught, learned by observation
Gardner: Linguistic (sensitivity to words), Logical-mathematical (abstract, identifying problems, seek explanations), spatial (accurately perceive world and recreate), musical (sensitivity to musical tones), bodily-kinaesthetic (graceful expression of body), intrapersonal (use own emotions to guide), interpersonal (identify other’s emotions and intentions and act on them), naturalist (identify other animals and explain relationship between them) BUT is kinaesthetic really cognitive? and lots of these intelligences correlate
IQ (Stanford-Binet) = mental age/chronological age x100
40-50% genetics, Pregnancy & childbirth – foetal growth, intrauterine infections, birth complications etc Family and quality of care (eg. institutional rearing decreases IQ), Schools & peer group – attitudes to work. Jefferis 2002: social class had bigger impact on IQ than birth weight. BUT lots of variablity still, eg. 76% concordance in identical twins reared apart and then 55% fraternal twins raised together but 1:3 children increase IQ by 30 points over 17 years. Community – socioeconomic deprivation, cohort effects, etc ID associated with other disorders, esp. ASD (OR=33), ADHD (OR=8.4), ADHD increases in prevalence with severity of ID (13% in mild, 30% in severe) Maternal physical health reported as less than good - OR=3.8
Mild ID in 2% population (IQ=70-35, semi-skilled work but still often require little support, often low socio-economic status and lower than average IQ in siblings but 14% CNS disorder) moderate (35-50, can do unskilled work without supervision and can live with little support)
Severe ID 0.4% population, i.e. 10 times higher than if IQ normally distributed (20-35) (minimum speech, assisted self-help skills, little difference between high and low socio-economic status and often average IQ in siblings but more 72% CNS disorder) Profound (<20) and often barely able to communicate own emotions. Often seizures and lower life expectancy.
Non-syndromic (ID solely, 50 genes) or syndromic (400 genes implicated)
Eg. Down’s syndrome, Fragile X, Tuberous sclerosis, William’s syndrome, Turner’s syndrome, Duplication and inverted duplication of chromosome 15q11-q15, Neurofibromatosis, Inborn errors of metabolism, [autosomal recessive] eg phenylketonuria, galactoseamia, homocystinuria etc, Cerebral palsy, Intrauterine infections, toxins etc
2) Perinatal e.g. neonatal jaundice, unusually obstetric complications.
3) Post-natal e.g. meningitis, trauma, etc, Poor countries: poor nutrition, iodine deficiency, infectious disease,
What are the symptoms, signs and genetics of Down’s syndrome?
Small head, Round face, Upslanting eyes & Epicanthic folds, Large fissured tongue, Low set ears, Short stature
Single palmar crease & Incurved little fingers, Hypotonia, Cardiac & GIT malformations, Risk onset deafness, leukaemia, Alzheimer disease
1 in 600 births, older mothers increase risk,
Commonest single cause severe Gen LD (accounts for up to 33% cases). IQ range 30- 70.
95% extra chromosome 21 from non-disjunction, 4% translocations, familial, 1% mosaics
Preschool – may have sensory sensitivities (eg to sounds), School age: hyperactivity and impulsivity marked, Autistic features – abnormalities in social reciprocity and interest in people, social withdrawal, stereotyped repetitive behaviours, Adolescents: risk depression, obsessive compulsive behaviour
What are the symptoms, signs and genetics of Tuberous sclerosis?
Skin lesions- areas of hypopigmentation (Woods light)
Adenoma sebeceum, 4-6 yrs, red and raised
Shagreen patch, lumbersacral region, raised and orange peel like
Epilepsy- infantile spasms
CT scan periventricular calcified tubors from 4 yrs
severity of learning difficulty linked to severity of seizures; <50% have ID
Cognitive: dyspraxia, speech delay, dyscalculia.
Childhood: ADHD in 50%; inattention in 90%
Association with autistic features in up to 50%
Emotional disorders may arise in adolescence, poor peer relationships.
Prevalence ~ 1 in 6 000, Autosomal dominant; but 2/3 cases from de novo mutations, Two genes can cause the disorder,
TSC1 chromosome 9q34 - codes hamartin
TSC2 chromosome 16p13 - codes tuberin
Hamartomas found in any tissue; Neural abnormalities: cortical tubers, cortical dysplasia, white matter abnormalities, subependymal giant cell astrocytomas.
Big variation in severity
What are the signs, symptoms and genetics of fragile X syndrome?
Minimal below 10yrs more pronounced as get older, large head with high forehead, Prominent ears, Mid facial hypoplasia and prognathism, Macroorchidism in adolescence, Connective tissue problems, Joint laxity, Flat feet, Occasionally mitral valve prolapse, Epilepsy in 23% often ceases in adolescence
Commonest heritable form of mental retardation
1 per 4000 males, partial phenotype in 1per 8000 females, Deficiency or absence of fragile X mental retardation protein 1 (FMR1), Expansion of CGG trinucleotide repeats in FMR1 gene on X chromosome at Xq27.3, normal 5-20; F-X ~200 repeats prevents the FMR1 protein being made, transcription inhibited
Unaffected mothers have 50-199, children have 10% chance of full blown syndrome, higher in known families:- 60-80%
Learning difficulties, profound to mild but on average
Boys IQ most < 50, Girls IQ ~ 60-80, Cognitive deficits – short-term visuo-spatial memory deficits, impaired motor planning, repetitive & impulsive interactional style., Speech –autistic style of conversation, Immature expressive syntax, Perseverative language, Social anxiety, shyness with gaze avoidance, Mood disturbance, anxiety, Often inattentive, restlessness, fidgety, Rate of autism 5% in Frag-X population and vice versa in autistic population
What are the signs, symptoms and genetics of Williams syndrome?
- Facial Features. All the children have a facial similarity, referred to as ‘elfin’ features. They include a wide mouth, with large, slack bottom lip; very retrousse nose with flattened bridge; slightly ‘bulgy’ cheeks; irregular teeth widely spaced; sometimes a squint.
- Early Problems. can include low birth weight, ‘late for dates’, slow weight gain - sometimes weight loss; below average growth; very slow feeding, restless sleeping, and irritability; sometimes a hernia, a squint and excessive vomiting leading to dehydration and constipation. Some babies - raised calcium level.
- Heart Problems. Supravaluvular aortic stenosis.
The incidence is approximately 1 in 7500; occurs sporadically. By 2002 over 1300 cases were known in the UK, > 90 % cases micro deletion of part of chromosome 7 at 7q11.2 which includes > 20 genes: including, Elastin-> connective tissue probs eg cardiac., Lim kinase 1 (LIMK1) expressed in brain linked to visuospatial anomalies., General transcription factor II (GTF21) linked to ID
- Low intellectual ability. Verbal and non-verbal abilities dioscrepant; verbal IQ ave 70; visuospatial skills ~2.5 SD below population norms.
Language acquisition delayed; unusual language dev, weak pragmatics of speech. - Social interactions: lack reciprocity, but may have good empathy, interested in faces.
- Hyperactivity in early years; Inattention, extreme uninhibited behaviour, excessive talking, over-friendliness with strangers; while being unable to make friends with peers. Obsessional interest in certain things: e.g. cars, trains, hoovers, wheels, etc. Fears eg heights, open stairs, uneven. Emotional immaturity & lability.
- Hypersensitivity to Noise. about 90% show great distress on hearing sudden loud noises, eg balloons bursting, fireworks, etc.
What is the management for ID?
Early detection
Parental genetic counselling and support
Early treatment e.g. for inborn errors of metabolism
Management of comorbid physical disorders eg epilepsy
Helping parents manage challenging behaviours
Treatment of psychiatric disorders – behaviourally, drugs etc
Education: special schools; mainstream- with support
What early risk factors affect mental illness as adult?
1/2 adults with mental illness had diagnosis of mental illness by 15yo, 3/4 by 18yo.
Parental psychopathology (eg postnatal depression/ substance abuse).
Genetics/ inheritance: ASD, BD, SZ, ADHD, etc.
Poverty/deprivation (may cause behavioral problems in the parents or increase the risk of child abuse)
Stressful Life Events: Parental death/divorce/frequent moves, Childhood Maltreatment
What is the Developmental Origins of Health and Disease (DOHaD)?
Barker hypothesised: quality of fetal growth and development predicts risk for range of chronic NCDs Barker’s observations formed basis of DOHaD hypothesis: intrauterine signals that compromise fetal growth also “program” tissue differentiation in a manner that predisposes to later illness - Hales 1991 shows more people with lower birth weights have impaired glucose tolerance
Associated with altered cell number, proliferation, size and altered intracellular organisation, DNA methylation and modified gene expression and signalling, altered cellular/metabolic function and appetite, lipogenesis.
South London Child Developmental Study supports maternal depression in utero increases risk child psychopathology (Pawlby 2013) and Avon Longitudinal Study of Parents and Children (ALSPAC) Glover 2002 showed untreated maternal mental illness has long lasting effectson psychological development of the child
prenatal Depression – 10-15% -> low birth weight and premature birth (Grote, 2010) -> infant cognitive, behavioural and emotional problems (O’Connor 2002), and adolescent and adult psychiatric disorders (Rice 2010)
Girls more affected than boys (Quarini et al, 2016)
Odds Ratio for offspring depression at 18 was 1.55 (95% c.i. 1.03-2.34) for girls and 0.54 (0.23-1.26) for boys. No interaction with SES
