Reducing Risk of Getting Schizophrenia

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Reducing Risk of Getting Schizophrenia
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Cannabis

• Over 30 published scientific research papers
  linking marijuana to schizophrenia
• Regular cannabis users by age 15 are four times
  as likely to have a diagnosis of schizophreniform
  disorder at age 26 than controls. (Arseneault et
  al 2002)

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Interaction with pre-existing psychosis
Cannabis
T1
No pre-existing psychosis
Pre-existing psychosis
2.2
54.7
T3
American Journal of Epidemiology, 2002
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Action

• Elimination of cannabis use would reduce the
  incidence of schizophrenia by approximately 8
• Discourage cannabis use in adolescence under the
  age of 18
• Discourage cannabis use in adolescence with FH
• Discourage cannabis use in adolescence with
  schizotypal traits.

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Urbanicity

• Individuals who spent their first 15 years of
  life in a highly urban area were nearly three
  times as likely to be diagnosed with
  schizophrenia, compared with people who grew up
  in rural areas. (Pedersen CB and Mortensen PB
  2001).
• A fifth to a third of individuals exposed to both
  the urban upbringing and the genetic risk
  factors attract the disorder because of their
  coparticipation. (van Os et al 2004)

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Do genes enhance urban risk? (n7076)
FH
?29.1, df1, P0.003
FH-
Population density
Am J Psychiatry, 2004
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Action

• Living outside a city before age 15 may reduce
  chances of getting schizophrenia
• Avoid raising up children in dense urban
  environment especially if FH

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Dysfunctional families

• Risk of getting schizophrenia (for children
  genetically predisposed to schizophrenia) can be
  up to eight times higher in high stress
  "dysfunctional families" vs. low stress
  households (Tienari et al 2004)

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Action

• Attempt to keep stress levels in the family
  environment at a relatively low level. Learn how
  to manage stress well. Stress Information.

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Pregnancy Infections

• Mothers who suffer from flu, viruses and other
  infections during the first trimester of
  pregnancy are at significantly increased risk of
  schizophrenia - up to seven times higher than
  children who are not exposed to flu/viruses
  during the first trimester of pregnancy. (Brown
  et al 2004)

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Action

• Become pregnant only after (at least several
  weeks after) taking a vaccination shot. Make
  extra efforts to avoid exposure of mother to
  influenza and other viruses during pregnancy.

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Obstetric Complications

• Risk for schizophrenia is four times higher for
  children who suffer from hypoxia during
  childbirth (Dalman BJP 2001)

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Action

• For reduced risk of children with schizophrenia,
  mothers should make extra efforts to avoid any
  possible delivery complications and to be in the
  best possible hospital environment in case
  complications do occur.

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Paternal Age

• Children born to fathers aged over 50 could be as
  much as four times more likely to develop
  schizophrenia than those born to fathers aged 21
  to 24(Rasmussen et al 2004 BMJ)

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Action

• For reduced risk of children with schizophrenia,
  men may choose to have children while they are
  younger (under 40) rather than older.

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PREVENTION upon indicators of developmental
vulnerability
mission Impossible

• the great majority of preschizophrenia children
  scoring well within the normal range.
• predictive value will be too low for the purpose
  of screening and prevention.

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Prepsychotic Expression of Illness
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Continuity Prediction
Psychotic symptom
7000
1 year
5500
Psychotic disorder
2 years
4700
Hanssen, Bak et al, 1998
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CIDI ratings at T1 as independent predictors of
being incident patient at T3
Hanssen et al, 2000
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The number of people screening positive for
subclinical psychotic experiences who needed to
be treated to prevent one case of full-blown
psychoticdisorder
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• Early intervention in the general population is
  not feasible, at least not on the basis of the
  subclinical psychosis screening criterion.
• The answer is increase Prevalence from 1 to say
  50 . Then PV will be 50 .

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Making schizophrenia more predictable but for
fewer patients
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Sample Enrichment Strategy

• most widely used approach but possibly also the
  worst understood.
• the predictive value of any factor, whether it be
  schizotypal symptoms, sex, color of the eyes, or
  any other random variable, would have been at
  least 50

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Predictors of schizophrenia dividing the high
risk ill group from other high-risk participants
Johnstone et al 2004 BJP
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Filter model of psychotic symptoms and psychotic
disorder
5. Psychiatric hospital
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ASPIS (N 2000)

• SCHIZOTYPY
• COGNITION
• GENES

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Endophenotypes for Schizophrenia
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Candidate genes for Schizophrenia
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Effect of COMT genotype on Schizotypal Dimensions

• COMT GENOTYPE
• VAL / VAL
• DOPAMINE
• VAL / MET
• MET / MET

• SCHIZOTYP. PHENOTYPE
• POSITIVE
• NEGATIVE
• DISORGANIZED
• PARANOID

Stefanis et al. 2004 Biol. Psychiatry
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COMT GENOTYPE EFFECT ON NEGATIVE SCHIZOTYPY ASPIS

• Young conscripts (n542) with lower level of
  dopamine transmission in PFC, score
  significantly higher on negative schizotypal
  items, related to social isolation and
  indifference for social contact.

Stefanis et al. 2004 Biol. Psychiatry
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DOPAMINE Tuning Cognitive Performance

• Low levels of dopamine transmission in PFC
  associated with increased inconsistency of
  response (noise) during cognitive tasks

Stefanis et al. American Journal of Psychiatry
(in press)
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