1. Aetiology: Part 1
Mike Akroyd, 9th May 2014

2. Aims Illustrate how aetiology fits into MRCPsych:
Paper 1 and beyond
Explore aetiological factors of general adult psychiatric illness
(Old age and child in part 2, in 2 weeks)

3. Objectives “By the end of this session I will be able to...”
Describe basic aetiological concepts
Apply aetiological factors to the biopsychosocial model
Identify aetiological factors involved in general adult psychiatric disorder
Answer some exam questions on the above

4. Why aetiology? We want to understand causes of mental disorder
Identification of at-risk individuals
Suggestion of management approaches
Possibility of preventive interventions
Patients (or parents...) want to know “am I to blame?”
...and it accounts for c.12/200 questions in Paper 1...

5. Aetiological theory Two broad categories of explanatory model
Reductionist
Understand causation by tracing back to simpler stages
E.g. schizophrenia caused by faulty neurotransmission in specific part of brain
(narrow) medical models
Non-reductionist
Problems relate to wider issues
E.g. schizophrenia caused by patient’s family
Sociological models

6. Aetiological factors Genetic Psychological Psychodynamic Social
Political
Environmental
Behavioural
Developmental

7. Biopsychosocial formulation
Predisposing
Genetics IQ
Personality
Family
Social class
Marital status
Precipitating
Illness
Drugs
Traumatic event
Unemployment
Divorce
Perpetuating
Chronic illness
Withdrawal
Hopelessness
Ongoing unemployment

8. Basic aetiological terms
Heritability
“Proportion of liability to a disorder in a population that is accounted for by genetic effects”
How much of the aetiology is likely to be accounted for by genetics?
(As opposed to environment)
Expressed in percentage term
Applied to population, not individual
Derived from difference in concordance between MZ and DZ twins

9. Heritability estimate
Disorder
Heritability estimate
Schizophrenia
80%
Major Depression
40%
Bipolar Affective Disorder
Generalised Anxiety Disorder
30%
Panic Disorder
Phobia
35%
Alcohol Problem/Dependence
60%

10. Basic aetiological terms
Not everything that runs in families is genetic...
Religion, Football team
Equally, not everything passed on shows itself
Concept of penetrance
Likelihood that having a particular genotype results in manifestation of associated characteristic.
Relatively few conditions fully penetrant.

11. Basic statistical concepts
Lifetime prevalence
Risk
Relative risk

12. Lifetime prevalence
What proportion of people will develop a given illness in their lifetime?
Lifetime prevalence of schizophrenia = 1%
1 in 100 will develop schizophrenia in their lifetime

13. Risk Risk = Chance = Probability
Probability that a given event will occur
In a given timeframe
What is the probability that a person will develop schizophrenia across their lifetime?
1/100 develop schizophrenia
Risk = 0.01

14. Relative risk
Ratio of risk in a group exposed to a certain risk, compared to a group not exposed.
i.e. Risk in exposed group
Risk in unexposed group
If relative risk =1, no difference between groups
If relative risk >1, exposed group more likely to develop disorder
If relative risk <1, exposed group less likely

15. Relative risk Cannabis use and schizophrenia
Lifetime prevalence (risk) of schizophrenia = 1/100
Risk in cannabis users = 5/200
Relative risk of schizophrenia in cannabis users?
5/200 = 5/200 = 5 = 2.5
1/ /

16. General Adult Aetiology
Schizophrenia
Bipolar affective disorder
Depression
Anxiety disorders
Dependency

17. Schizophrenia Bio Psycho Social Predisposing 80% HERITABILITY
Birth complications
Maternal influenza
Winter birth
Paternal age
Failure to negotiate P-S position
Family patterns
Social class
Urbanicity
Migration
Precipitating
Cannabis use
Non-specific life events
Perpetuating
Chronic illness
Withdrawal
Hopelessness
Ongoing unemployment

18. Schizophrenia – Genetics
80% heritability
Complex genetic disorder
Or group of disorders

19. Schizophrenia – Genetics
Non-identical twin: 10-15%
Child of 2 patients: 40%
4-5.5%
10-15%
42-50% 2%
12-16% 6%

20. Schizophrenia – Genetics
Susceptibility genes
Neuregulin (NRG1) – strong evidence
Dysbindin (DTNBP) – strong evidence
D-Amino acid oxidase activator (G72)
Regulator of G-protein signalling-4 (RGS-4)
Disrupted in schizophrenia (DISc-1)
Metabotropic glutamate receptor 3 (GRM3)
Catechol-O-methyl transferase (COMT) (also implicated in velocardiofacial syndrome)
D-aminoacid oxidase (DAAO)
5-HT2A receptor (HTR2A)
Dopamine D3 receptor (DRD3)

21. Schizophrenia – Genetics
1st degree relatives of patients with schizophrenia
Risk of schizophrenia
Risk of schizoaffective disorder
Risk of schizotypal personality disorder
1st degree relatives of patients with schizoaffective

22. Schizophrenia – Social
Lower social class
Competing hypotheses
Low predisposing IQ, hardship?
Social drift in prodrome/illness?
Urbanicity
Migration
Higher risk in migrants
Particularly 2nd generation
UK migrants from Afro-Caribbean higher risk than indigenous UK population or non-migrating Afro-Caribbean

23. Schizophrenia – Environmental
Obstetric complications
Reported in retrospective studies
Not consistently replicated in prospective studies
Maternal influenza
2nd trimester influenza exposure
Mixed evidence
Winter birth
Effect shown in N+S hemispheres
Cannabis use
Andreasson’s Swedish military conscripts
Dose-dependent relationship
Paternal age
Some evidence

24. Schizophrenia – Organic
Metachromatic leucodystrophy
35% develop schizophrenia
Velocardiofacial syndrome (aka Di George)
Schizophreniform and affective psychosis in 30%
Huntington’s disease
Associated with schizophreniform/affective psychosis
Increased risk in epilepsy (birth of ECT...)

25. Schizophrenia – Neurological
Developmental
Distinguishable from peers at c.11
Hostility toward adults
Language delays
Poor rapport
Isolation from peers
Low IQ
Prevalence of schizophrenia in LD = 3%

26. Schizophrenia – Psychological
Psychodynamic
Freud – Narcissism
Klein – Failure to negotiate paranoid-schizoid position

27. Schizophrenia – Psychological
Family
Fromm-Reichmann - Deviant role relationships
(“schizophrenogenic mother”)
Lidz – Abnormal family patterns
“Marital skew” – one parent yields to other’s eccentricity
“Marital schism” – contrary views, divided loyalties
Bateson & Wynee – Disordered communication
“Double bind” – instruction contradicted by covert instruction
Not routinely used
Scarce data, induction of guilt

28. Schizophrenia – Precipitants
Non-specific life events precede first onset & relapses
Increased rate in preceding 3 weeks

29. Schizophrenia – Relative risks
Factor
Relative risk
Cannabis use (heavy) 6
Epilepsy
2.4 (or 9...)
Migrants
2.7
In 6 months post ‘Life Event’ 2
Winter birth
1.1
Urban birth
2.4
Cannabis use (overall)
2.5
Maternal influenza
(Up to 7...)

30. Schizophrenia – Aetiological theory
Neurodevelopmental
Leading hypothesis
Structural brain abnormalities precede symptom onset
Cognitive/social impairment in childhood
“Soft” neurological signs
Perinatal risk factors
Abberant connectivity
Inadequate integration of brain regions
Stress-diathesis model
Vulnerability from early factors
Later stressors trigger onset, determine course

31. BPAD Lifetime prevalence = c.1% Heritability = 80-85%
First degree relatives:
Risk of BPAD (7-10% vs 1%)
Risk of unipolar depression (20-30% vs 10-20%)
Risk of schizoaffective disorder
And risk of BPAD if first degree relative has:
Unipolar depression (2%) (some dispute)
Schizoaffective disorder (4.8%)

32. BPAD Genetics Social Psychological Precipitating factors
Tyrosine hydroxylase; COMT; 5HT transporter; BDNF
Social
Higher socioeconomic class; divorced/single
Psychological
Cyclothymic personality predisposes
Precipitating factors
Life events
“Kindling effect”

33. Depression Lifetime prevalence = c.10-20%
Heritability estimates vary (40-75%)
Lower MZ concordance
First degree relatives:
Risk of unipolar depression (20-30%)
Risk of BPAD 2%? 1%?

34. Depression Genetics Social 5HT transporter gene
Risk in unemployed, divorced, separated
Risk if poor social support, isolation
Brown & Harris – 3 factors in women
Not working outside the home
Lack of confiding relationship
3+ children under 14

35. Depression Environmental Organic Precipitating factors
Loss of parent before 11
Family discord, separation, divorce
Childhood sexual abuse
Organic
Risk in HIV, MS, endocrine disorders
Iatrogenic: L-Dopa, methyldopa, ß-blockers, steroids
Precipitating factors
Kindling

36. Depression – Psychological
Relationship with parents
Non-caring/overprotective
Attachment problems (e.g. maternal depression)
Personality
High need for approval
Neuroticism (Eysenck)
Beck’s cognitive triad
1. Self: negative self-perception
2. World: hostile, demanding
3. Future: expectation of suffering, failure

37. Depression – Psychological
Freud, Abraham
Disturbance of oral phase predisposes
Real/imagined loss of an object
Object introjected (defence)
Invokes love and hate
Anger toward lost object directed inwards
Seligman
Learned helplessness

38. Suicide UK suicide rate c.1/10,000 Genetics Organic
Men (17/100,000) > Women (5/100,000)
Genetics
Positive family history increases risk
Organic
Associated with: Epilepsy; MS; AIDS; Huntington’s
Low 5-HIAA in CSF of completed suicide
Presynaptic marker of 5HT function

39. Suicide – Social Risk in: Durkheim: 4 types of suicide
Males, unemployed, Caucasian, migrants
Low social class, professionals, fall in status
Married, with children
Wartime
Durkheim: 4 types of suicide
Egoistic – Not integrated
Altruistic – Excessive integration
Anomic – Disrupted integration
Fatalistic – Escape from oppression

40. Suicide

41. Anxiety disorders OCD PTSD Prevalence = c.2-3%; 35% in 1st degree
Risk in single
35% premorbidly anankastic
Freud: Regression to anal phase
PTSD
Women > Men
Risk in single/divorced/widowed; withdrawn, low SE
Risk in alcohol misuse, previous childhood trauma
Precipitated by
Interpersonal violence (assault, rape, combat)
External locus of control (natural disaster)

42. Anxiety disorders Phobias Panic disorder
31% of 1st degree relatives will have a phobia
‘Prepared learning’ – some evolutionary benefit
E.g. snakes
Conditioning
Development of phobia following stressor
Panic disorder
Heritability = c.30-40%
1st degree relatives c.3x more likely

43. Alcohol Alcohol dependence Heritability = c.60% Social learning theory
Biological sons adopted away retain risk
Social learning theory
Comorbid psychiatric disorder is common
Rate of dependence mirrors rate of consumption

44. Drugs 4 factors contribute to drug use 1. Availability of drugs
2. Vulnerable personality
School record, truancy, thrill-seekers, impulsivity
3. Social environment
Condoned use, unemployment, homelessness
4. Pharmacological factors
Not every user becomes an abuser
Risk if create positive feeling or alleviate stress

45. 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 ?
Kindling effect
Abberant connectivity
Neurodevelopmental hypothesis
Stress-diathesis model
Social model

46. A mother wants to know what is the risk of schizophrenia in her son who smokes cannabis?
Four-fold increase in risk
Two-fold increase in risk
Four-fold decrease in risk
Two-fold decrease in risk
No association between cannabis and schizophrenia

47. Which of the following does not increase the risk of developing bipolar disorder?
Family history of depression
Family history of schizoaffective disorder
Family history of schizophrenia
Cyclothymic personality
Family history of bipolar disorder

48. Which of the following is not a vulnerability factor for depression as described by Brown and Harris?
Lack of confiding relationship
Loss of parent before age of 11
Not working outside the home
Having 3 or more children under the age of 14
None of the above

49. 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?
Anomic
Altruistic
Egoistic
Fatalistic
Holistic

50. Which of the following risk factor is likely to be causative in a young man diagnosed with schizophrenia?
Alcoholism
HLADR2 gene
Being a migrant
Having lost his mother before the age of 14
Living alone