3. I wanted to know
What is the cause of psychosis?
Eventual aim to prevent it.
+
4. What does the webb say?
Website of Canada’s largest mental health
research institution is enigmatic…
“No single cause has been found for
schizophrenia, although there is a clear genetic
link. Research has given us clues in the search
for better ways to diagnose and treat the illness.”
+
5. Two camps
+
Biological Social
Professional view Community
8. Genetics
Multiple genes may
be involved
These may be
inherited or sporadic
genetic changes
Strongest evidence
for two genes
dysbindin and
+ neuregulin
9. Obstetrics
Obstetric problems
common
Non specific risk factor
with small impact on
schizophrenia risk
Hypoxia before or
during birth may impact
on brain development
increasing risk of later
schizophrenia
+
10. Obstetrics
+
Winter and spring births more likely to develop schizophrenia
could be due to viral infection or vitamin D
11. Infections
+ Reports vary some show link between foetal exposure to flu and later risk of
schizophrenia others do not
Other maternal infections have been studied but the results are not conclusive
12. Changes in structure
Biological insult to the
developing brain leads
to problems later on.
Decrease in grey matter,
enlargement of
ventricles, focal
alteration of white matter
+
13. Changes in function
Problems in dopaminergic pathways in the
limbic system and parts of the pre-frontal
cortex but other pathways and
neurotransmitters are involved
In acute psychosis increase in dopamine
synthesis, dopamine release, and synaptic
dopamine concentrations
+ Diminished brain response to new stimuli and
decreased ability to suppress brain activation
in response to repeated stimuli
15. Childhood
A number of social factors increase the risk of developing
schizophrenia:
Separation from parents for more than a year in childhood
Social adversity in childhood (more adversity more risk)
+ Psychological trauma / Bullying
Being born and brought up in a city
16. Stress
Increased rates of schizophrenia if you:
live in neighborhoods that are stressful
have numerous daily hassles
+
17. Urban environment and mental illness
Increased rates not due to drift
alone
Being born and brought up in a city
are risk factors.
The risk increases as the size of
the city increases.
Longer you live in a city when you
are young, the higher your risk for
developing psychosis
+
(Boydell and McKenzie, 2008).
17
18. Stress of Migration increases risk of
schizophrenia. Cantor Graae and Selten
2005
+
19. Racism psychosis risk factor
for psychosis
Estimated prevalence of psychosis
All Ethnic Minority Groups
4.0%
3.0%
2.0%
+ 1.0%
0.0%
No Verbal Physical* No Some Most*
only*
Racial harassment British employers discriminate
Karlsenn et al Psychological Medicine 2005 Sept 29-1-9
20. Social model
Schizophrenia is the result of trauma and stress which
impact on the child or adult and lead to a breakdown
The more social stress, the higher the risk of psychosis
Mechanisms are psychological model put forward by
Adverse experiences increase the likelihood of negative
self-esteem and induce an externalizing attributional style.
In concert with difficulties in theory of mind lead to
tendency to anticipate social encounters as a threat and
+ prevent reality testing
25. Miasma theories
Prior to modern medicine disease attributed to
spiritual or mechanical causes.
elements
humours
miasma – bad air arising out of dirt and decaying
organic matter
+
26. sanitising slums
Early public health built on what came before –
miasma and humours etc
Risk place based not due to individuals.
+
27. Germ theory
Undermined by
Cartesian revolution – mind and body dichotomy
Discovery of bugs which cause disease. Germ theory
Germ theory mono-causal approach
Cause investigation moved from the community to
the laboratory
+
28. Epidemiological triangle
Mono-causal germ theory has problems
Exposure does not always lead to illness
Generally exposure necessary but not sufficient
Epidemiological triangle approach
Disease a product of an interaction between an agent, the
host and the environment.
Host & environment determine exposure and or
susceptibility
+
29. Web of causation
Epidemiological triangle useful for infectious
disease
Problematic for chronic illnesses or degenerative
illnesses,
No specific agent or exposure but a web of
causation.
+ Complex interactions of many factors which form
interlocking chains of events.
30. Multi-level causation
Susser & Susser – public health and psychiatrist
come together
Chinese box / Russian dolls model of causation:
inter-connected but separate levels of causation
and investigation
+
33. 4 D model
Risk factors act at different levels
Individual – eg bullying
Ecological – eg Urban upbringing
Interaction …
+ Time – eg sensitive periods for cannabis use
34. Causation models build on each
other and are not in competition.
Trade-offs are a chance to think
in a different way.
+
36. Urban environment and mental illness
Urban environment changes the
exposure to risk factors
Malnutrition and infection during pregnancy
Drug use
Life events and chronic daily hassles
Social isolation
And changes the action of risk factors
+
Clustering of individuals with schizophrenia in deprived
areas occurs only in urban environments
Genetic vulnerability amplified
36
37. Urban environment
Impact on schizophrenia risk
dependent on genetic risk
No genetic risk no increased risk of
urban environment
Impact growing
+
38. Incidence of psychosis by ethnicity and
social cohesion
Predicted incidence rate (per 100,000
80
70
60
person-years)
50
40 White
BME
30
20
+ 10
0
Low Medium High
Social cohesion and trust (ward-level)
38
41. A new science
Mind not the Brain
Epi-genetics not genetics
Social impacts on biological mechanisms
+
42. How does all this cause mental illness
Mental illness lies in the mechanisms we use to
adapt
Biology and psychology that adapts to the
environment
They are problems of adaptation and
acceptance of different types of adaptation
Both lead to changes in behavior and thoughts
Our biology and psychology are linked
+
43. Development of brain depends on
environment
Development of brain and mind depend on
environmental stimulation
Normal development of neuronal connectivity
depends on impacts of environment during
sensitive periods of development
+
44. Environment changes molecular function
Epi-genetics refers to the reversible regulation
of various genomic functions, occurring
independently of DNA sequence,
Mediated through changes in DNA methylation
and chromatin structure.
Epigenetic mechanisms help us develop and
regulate gene function and mediate
+ environmental effects on genes
Other candidates – neurogenesis and
inflammation
45. Early neglect has a longer-term
trajectory
Early neglect and other environmental insults that
impact on stress signaling.
This causes impaired neuronal responsiveness
and symptoms of pre-frontal cortical dysfunction.
+
Impaired pre-frontal cortex functioning observed in
schizophrenia.
46. Trajectory then medicated by social
world
Sensitive periods reflect the chronology of
development of psychological processes in
children
Psychotic symptoms in adolescence transient and
sub-clinical
But repeated exposure to environmental risk
factors may cause persistent and more severe
+ symptoms
47. Vicious cycle can develop
Likelihood and severity of symptoms also reflect
sensitization
Early life adversity makes you more sensitive to
stress and more likely to produce sub-clinical
psychotic symptoms
Early life adversity or psycho-stimulant use leads to
altered dopamine transmission and sensitization of
+ mesolimbic system neurons linked to development
of psychotic symptoms
48. van Os and Kapur Lancet
2009
A mixture of dopamine dysregulation and
aberrant assignment of salience to stimuli,
together with a cognitive schema that attempts
to grapple with these experiences to give them
meaning, might lead to the development of
psychotic symptoms.
Alterations in affective state (depression or
mania) and some ways of thinking, such as a
+ tendency to jump to conclusions, might combine
with the dopamine dysfunction to increase the
risk of delusion formation
49. Searching for answers for my patients
Causes of psychosis are multi-level
Problems is mind not the brain
Social and biological working together
is the way forward
Where there is a difference between
two group there is a chance for new
+ knowledge
This new knowledge brings the
possibility of prevention