aetiology: part 2 mike akroyd, 4 th july 2014. aims illustrate how aetiology fits into mrcpsych: ...
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AETIOLOGY: PART 2
Mike Akroyd, 4th July 2014
Aims
Illustrate how aetiology fits into MRCPsych: Paper 1 and beyond
Explore aetiological factors of older adult and child psychiatric illness (General adult covered in part 1 – handouts
available from Mandy if anyone needs one)
Objectives
“By the end of this session I will be able to...” Identify aetiological factors involved in
older adult and child psychiatric disorder Answer some exam questions on the above
Older adults
Dementia Delirium
Alzheimer’s disease
c.50-60% of dementia Also commonest presenile dementia Identified genetic and environmental
factors?
Alzheimer’s disease – Genetic
Illness Gene Comments
Early onset familial Alzheimer’s disease
Presenilin 1 Chromosome 14
Presenilin 2 Chromosome 1
Amyloid precursor protein
On chromosome 21 – hence increased risk in Down’s syndrome
Late onset Alzheimer’s disease
Apolipoprotein E4(ApoE4)
Increases risk of developing disease
Heterozygotes (1 copy)
= 3 x risk Homozygotes (2
copies)= 10 x risk
Other alleles (E1,E2,E3) do not increase risk
Ubiquilin 1 Candidate gene
Alzheimer’s disease – Environmental No direct causality Possibility of interactions with genetic
factors
Alzheimer’s disease – Environmental Low educational attainment History of head injury Cerebrovascular disease History of depression High homocysteine levels Diabetes mellitus
(Aluminium exposure? – weak evidence)
?Damage making brain more vulnerable to neurodegeneration
Alzheimer’s disease – Environmental Some protective factors:
Use of NSAIDS Reduce risk by <50% Effect on APP metabolism
HRT Statins? Cognitive/physical activity in mid-life
‘Use it or lose it’
Other neurodegenerative disorders Dementia with Lewy bodies
15-20% dementias A ‘synucleinopathy’
(Like Parkinson’s diesease) Main feature is abnormal aggregation of α-
synuclein Association with ApoE4 Environmental factors not established
Other neurodegenerative disorders Parkinson’s disease
c.1% of over 55s Mostly idiopathic Rare autosomal dominant form
Mutations in α-synuclein, UCHL1, NR4A2, LRRK2 Rare autosomal recessive form
Mutations in parkin, DJ1, Pink1 Environmental risk factors
Toxin exposure, solvents, CO, well water Smoking and ?caffeine protective
Other neurodegenerative disorders Frontotemporal dementias
2nd most common cause of presenile dementia 7% of later life dementia Largely unknown aetiology
(aetiologies – several diseases within this umbrella: e.g. Pick’s; lobar atrophy; semantic dementia; MND + dementia)
1/3 have a 1st degree relative with FTD Familial FTD subgroups - autosomal dominant
inheritance Chromosome 17 – FTDP-17 Tau protein processing
Other neurodegenerative disorders Huntington’s disease
Single gene, autosomal dominant Complete penetrance New mutations are rare Chromosome 4p – encodes Huntingtin
Trinucleotide repeat CAG (encodes Glutamine) Normal = <30 repeats Huntington’s = >36 repeats ‘Anticipation’
Expansion increases in offspring Earlier age of onset
Vascular dementia
20-25% of dementias Prevalence increases with age
Roughly doubles with every 5 years of age Risk factors same as for other vascular
disease Smoking, diabetes, hyperlipidaemia
Other aetiological factors
Trauma Head injury Repeated trauma – dementia pugilistica
Organic Infections (HIV, vCJD, neurosyphillis) Metabolic (dialysis, hypo/hyperthyroidism,
Cushing’s) Deficiencies (B12, Folate) Toxins (alcohol, heavy metals, solvents) Normal pressure hydrocephalus
Delirium
15-30% of patients on medical/surgical wards
Increased risk in Older adults Existing dementia
Delirium
Medication Opiates, anticholinergics, sedatives, digoxin, diuretics, lithium, steroids
Physical illness Infections, hypo/hyperglycaemia, organ failure, thiamine deficiency, electrolyte imbalance
Neurological Tumour, head injury, infection, epilepsy
Toxins Alcohol, opiates, carbon monoxide
Don’t forget... Constipation, pain
Child and Adolescent
ADHD ASD Eating disorders
ADHD
Using DSM-IV ADHD criteria, UK prevalence = 3%
Using ICD-10 hyperkinetic disorder criteria = 1.7%
M:F = 3:1
Increasing prevalence Increased recognition?
ADHD – Genetics
Heritability = 60-90% Parents and siblings = 8 x increased risk Genes for dopamine receptors
implicated DAT1 (Dopamine transporter) DRD4 (Dopamine receptor)
ADHD – Birth & pregnancy
Prenatal
Maternal smoking – dose-dependent relationship with ADHD
Maternal cocaine use may increase risk
Maternal stress – increased serum cortisol – may increase risk
Perinatal
Very low birth weight = 2 x risk
Birth complication = increased risk (difficult to quantify)
ADHD – Environmental
No evidence for food additives increasing overactivity
Some evidence for lead intoxication and zinc deficiency
ADHD – Social
Chronic exposure to difficult early environment Eg. severe social deprivation increases risk
No evidence that parenting in normal range causes ADHD Parenting can alter course/prognosis
Maternal psychopathology and low socioeconomic status associated with ADHD
No association between large family size or paternal antisocial behaviour and ADHD
Autistic Spectrum Disorders
Lifetime prevalence of ASD = 1% Lifetime prevalence of autism =
0.1-.0.3% Autism: M:F = 4:1
ASD – Genetics
Heritability > 90%, MZ concordance up to 90%
Chromosomes 2, 7, 15 Siblings of probands with autism show
increased risk of range of cognitive abnormalities Supports idea of wider phenotype Siblings of probands:
Risk of autism 5%
Risk of ASD c.10%
Risk of autistic traits 20-30%
ASD – Birth & Pregnancy
Children with autism more likely to have suffered birth trauma
ASD – Organic
Organic brain disorder Larger brain volumes than controls Hypoactivation of amygdala,
frontotemporal areas 1/3 have high peripheral 5HT levels Associated with Fragile X, Rett
syndrome, tuberous sclerosis
No evidence for relationship between autism and schizophrenia
Eating disorders
Anorexia – 0.7% of female pupils/students M:F = 1:10-20
Bulimia – c.1% of women 16-40 M:F = 1:10
ED – Genetics
Anorexia MZ concordance = 55%; DZ concordance =
5% Bulimia
MZ concordance = 35%; DZ concordance = 30%
(Higher heritability in anorexia) 1st degree relatives of people with
anorexia Increased risk of any ED
ED – Genetics
Family history of other illnesses/traits increase risk of ED
Family history of:
Associated with anorexia
Associated with bulimia
Depression
Substance misuse
(especially alcohol)
Perfectionism
Obesity
ED – Family influences
NICE recommend FT in anorexia Parenting
Low contact, high expectation, parental discord, physical or sexual abuse
“Enmeshment, over-protectiveness and lack of conflict resolution” – Minuchin, 1978
Anorexia dissipates family tensions Family attitudes to:
Body shape, exercise, food (“family dieting”)
ED – Other
Social Western societies Occupational/recreational need for certain
body shape Competitive riding, ballet
Pre-morbid personality Low self-esteem Anxiety disorders Anorexia – perfectionism Bulimia – obesity, early menarche
Which of the following theories suggests that schizophrenia occurs when individuals who are vulnerable to the disease undergo a life stress which precipitates the initial episode ?
a. Kindling effect
b. Abberant connectivity
c. Neurodevelopmental hypothesis
d. Stress-diathesis model
e. Social model
A mother wants to know what is the risk of schizophrenia in her son who smokes cannabis?
a. Four-fold increase in risk
b. Two-fold increase in risk
c. Four-fold decrease in risk
d. Two-fold decrease in risk
e. No association between cannabis and schizophrenia
Which of the following does not increase the risk of developing bipolar disorder?
a. Family history of depression
b. Family history of schizoaffective disorder
c. Family history of schizophrenia
d. Cyclothymic personality
e. Family history of bipolar disorder
Which of the following is not a vulnerability factor for depression as described by Brown and Harris?
a. Lack of confiding relationship
b. Loss of parent before age of 11
c. Not working outside the home
d. Having 3 or more children under the age of 14
e. None of the above
A person who feels like he has lost his place is society due to being made redundant goes on to commit suicide. According to Emile Durkheim what type of suicide would that be?
a. Anomic
b. Altruistic
c. Egoistic
d. Fatalistic
e. Holistic
Which of the following risk factor is likely to be causative in a young man diagnosed with schizophrenia?
a. Alcoholism
b. HLADR2 gene
c. Being a migrant
d. Having lost his mother before the age of 14
e. Living alone
Which of the following genes has no association with Alzheimer’s disease?
a. DRD4b. Ubiquilin 1c. Presenilin 2d. APPe. ApoE
Protective factors for development of Alzheimer’s disease do not include:
a. Use of aspirinb. Cognitive activityc. High serum homocysteined. Use of HRTe. None of the above factors are
protective
In families with Huntington’s disease, the illness tends to present earlier in successive generations. This phenomenon is known as:
a. Heritabilityb. Penetrancec. Expectationd. Anticipatione. Incidence
ADHD is associated with increased maternal serum:
a. Dopamineb. Cortisolc. Serotonind. Testosteronee. GABA
Heritability in autism is thought to be
a. 15%b. 30%c. 50%d. 75%e. 90%
Autism is not associated with:
a. Fragile X syndromeb. Tuberous sclerosisc. Angelman syndromed. Rett syndromee. Birth complications
Which of the following aetiological factors favours a diagnosis of bulimia over anorexia?
a. History of perfectionist traitsb. Family history of depressionc. History of obesityd. Enmeshed parenting stylee. History of sexual abuse
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