AETIOLOGY: PART 1

Mike Akroyd, 9th May 2014

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)

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

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...

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

Aetiological factors

Genetic Psychological Psychodynamic Social Political Environmental Behavioural Developmental

Biopsychosocial formulation

Bio Psycho Social

Predisposing Genetics IQPersonality

FamilySocial class

Marital status

Precipitating IllnessDrugs

Traumatic event

UnemploymentDivorce

Perpetuating Chronic illness WithdrawalHopelessness

Ongoing unemployment

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

Heritability

Disorder Heritability estimate

Schizophrenia 80%

Major Depression 40%

Bipolar Affective Disorder 80%

Generalised Anxiety Disorder 30%

Panic Disorder 40%

Phobia 35%

Alcohol Problem/Dependence 60%

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.

Basic statistical concepts

Lifetime prevalence Risk Relative risk

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

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

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

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 1/100 2/200 2

General Adult Aetiology

Schizophrenia Bipolar affective disorder Depression Anxiety disorders Dependency

Schizophrenia

Bio Psycho Social

Predisposing

80% HERITABILITY

Birth complications

Maternal influenza

Winter birthPaternal age

Failure to negotiate P-S

positionFamily patterns

Social classUrbanicityMigration

Precipitating Cannabis use Non-specific life events

Perpetuating Chronic illness WithdrawalHopelessness

Ongoing unemployment

Schizophrenia – Genetics

80% heritability Complex genetic disorder Or group of disorders

Schizophrenia – Genetics

12-16%

42-50%10-15%

2%

4-5.5% 4-5.5%

Non-identical twin: 10-15%Child of 2 patients: 40%

6%

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)

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 Risk of schizophrenia

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

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

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...)

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%

Schizophrenia – Psychological Psychodynamic

Freud – Narcissism Klein – Failure to negotiate paranoid-

schizoid position

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

Schizophrenia – Precipitants

Non-specific life events precede first onset & relapses

Increased rate in preceding 3 weeks

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...)

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

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%)

BPAD

Genetics Tyrosine hydroxylase; COMT; 5HT

transporter; BDNF Social

Higher socioeconomic class; divorced/single Psychological

Cyclothymic personality predisposes Precipitating factors

Life events “Kindling effect”

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%?

Depression

Genetics 5HT transporter gene

Social 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

Depression

Environmental 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

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

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

Suicide

UK suicide rate c.1/10,000 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

Suicide – Social

Risk in: Males, unemployed, Caucasian, migrants Low social class, professionals, fall in status

Risk in: Married, with children Wartime

Durkheim: 4 types of suicide Egoistic – Not integrated Altruistic – Excessive integration Anomic – Disrupted integration Fatalistic – Escape from oppression

Suicide

50%

17%

8%

8%

3%

14%

Mental heath diagnoses associated with suicide

AffectiveSchizophreniformPersonality disorderAlcohol dependenceDrug dependenceOther

Anxiety disorders

OCD 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)

Anxiety disorders

Phobias 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

Alcohol

Alcohol dependence Heritability = c.60%

Biological sons adopted away retain risk Social learning theory Comorbid psychiatric disorder is common Rate of dependence mirrors rate of

consumption

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

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