The cause of psychosisKwame McKenzie MD
Searching for answers for my    patients+
I wanted to know       What is the cause of psychosis?       Eventual aim to prevent it.+
What does the webb say?       Website of Canada’s largest mental health        research institution is enigmatic…       ...
Two camps+     Biological            Social     Professional   view   Community
Biological camp+
Genetics – highly heritable+
Genetics                  Multiple genes may                   be involved                  These may be                ...
Obstetrics                    Obstetric problems                     common                    Non specific risk factor ...
Obstetrics+     Winter and spring births more likely to develop schizophrenia        could be due to viral infection or ...
Infections+   Reports vary some show link between foetal exposure to flu and later risk of     schizophrenia others do no...
Changes in structure       Biological insult to the        developing brain leads        to problems later on.       Dec...
Changes in function     Problems in dopaminergic pathways in the      limbic system and parts of the pre-frontal      cor...
Social camp+
Childhood       A number of social factors increase the risk of developing        schizophrenia:           Separation fr...
Stress       Increased rates of schizophrenia if you:           live in neighborhoods that are stressful           have...
Urban environment and mental illness    Increased rates not due to drift     alone    Being born and brought up in a cit...
Stress of Migration increases risk of    schizophrenia. Cantor Graae and Selten    2005+
Racism psychosis risk factor    for psychosis                 Estimated prevalence of psychosis                           ...
Social model       Schizophrenia is the result of trauma and stress which        impact on the child or adult and lead to...
50:50+
Half full or half empty?+
Trade-offs are opportunities+
Models of causation+
Miasma theories       Prior to modern medicine disease attributed to        spiritual or mechanical causes.        elemen...
sanitising slums       Early public health built on what came before –        miasma and humours etc       Risk place ba...
Germ theory       Undermined by           Cartesian revolution – mind and body dichotomy           Discovery of bugs wh...
Epidemiological triangle       Mono-causal germ theory has problems        Exposure does not always lead to illness      ...
Web of causation     Epidemiological triangle useful for infectious      disease     Problematic for chronic illnesses o...
Multi-level causation       Susser & Susser – public health and psychiatrist        come together       Chinese box / Ru...
Multilevel causation of psychosis                             Environmental                       Interpersonal           ...
Russian dolls       molecular level       metabolic patho-physiology       individual level       group level       s...
4 D model     Risk factors act at different levels     Individual – eg bullying     Ecological – eg Urban upbringing  ...
Causation models build on each    other and are not in competition.    Trade-offs are a chance to think    in a different ...
The interest is in the    interactions+
Urban environment and mental illness       Urban environment changes the        exposure to risk factors       Malnutrit...
Urban environment       Impact on schizophrenia risk        dependent on genetic risk       No genetic risk no increased...
Incidence of psychosis by ethnicity and    social cohesion     Predicted incidence rate (per 100,000                      ...
+
Social and biological are not    two solitudes+
A new science       Mind not the Brain       Epi-genetics not genetics       Social impacts on biological mechanisms+
How does all this cause mental illness   Mental illness lies in the mechanisms we use to    adapt   Biology and psycholo...
Development of brain depends on    environment       Development of brain and mind depend on        environmental stimula...
Environment changes molecular function       Epi-genetics refers to the reversible regulation        of various genomic f...
Early neglect has a longer-term trajectory    Early neglect and other environmental insults that     impact on stress sig...
Trajectory then medicated by social    world       Sensitive periods reflect the chronology of        development of psyc...
Vicious cycle can develop       Likelihood and severity of symptoms also reflect        sensitization       Early life a...
van Os and Kapur Lancet    2009       A mixture of dopamine dysregulation and        aberrant assignment of salience to s...
Searching for answers for my patients       Causes of psychosis are multi-level       Problems is mind not the brain    ...
Thank you+
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Plenary Presentation: Kwame McKenzie, M.D., Medical Director at Centre for Addiction and Mental Health, Toronto, Canada

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Plenary Presentation: Kwame McKenzie, M.D., Medical Director at Centre for Addiction and Mental Health, Toronto, Canada

  1. 1. The cause of psychosisKwame McKenzie MD
  2. 2. Searching for answers for my patients+
  3. 3. I wanted to know  What is the cause of psychosis?  Eventual aim to prevent it.+
  4. 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. 5. Two camps+  Biological Social  Professional view Community
  6. 6. Biological camp+
  7. 7. Genetics – highly heritable+
  8. 8. Genetics  Multiple genes may be involved  These may be inherited or sporadic genetic changes  Strongest evidence for two genes  dysbindin and+ neuregulin
  9. 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. 10. Obstetrics+ Winter and spring births more likely to develop schizophrenia  could be due to viral infection or vitamin D
  11. 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. 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. 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
  14. 14. Social camp+
  15. 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. 16. Stress  Increased rates of schizophrenia if you:  live in neighborhoods that are stressful  have numerous daily hassles+
  17. 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. 18. Stress of Migration increases risk of schizophrenia. Cantor Graae and Selten 2005+
  19. 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. 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
  21. 21. 50:50+
  22. 22. Half full or half empty?+
  23. 23. Trade-offs are opportunities+
  24. 24. Models of causation+
  25. 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. 26. sanitising slums  Early public health built on what came before – miasma and humours etc  Risk place based not due to individuals.+
  27. 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. 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. 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. 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+
  31. 31. Multilevel causation of psychosis Environmental Interpersonal Individual+ Genetic molecular 31
  32. 32. Russian dolls  molecular level  metabolic patho-physiology  individual level  group level  societal+
  33. 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. 34. Causation models build on each other and are not in competition. Trade-offs are a chance to think in a different way.+
  35. 35. The interest is in the interactions+
  36. 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. 37. Urban environment  Impact on schizophrenia risk dependent on genetic risk  No genetic risk no increased risk of urban environment  Impact growing+
  38. 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
  39. 39. +
  40. 40. Social and biological are not two solitudes+
  41. 41. A new science  Mind not the Brain  Epi-genetics not genetics  Social impacts on biological mechanisms+
  42. 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. 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. 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. 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. 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. 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. 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. 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
  50. 50. Thank you+

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