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Reducing Risk of Getting Reducing Risk of Getting SchizophreniaSchizophrenia
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CannabisCannabis
OOver 30 published scientific research ver 30 published scientific research papers linking marijuana to papers linking marijuana to schizophrenia schizophrenia
Regular Regular cannabis cannabis users users by age 15 by age 15 are are four timesfour times as likely to have a diagnosis as likely to have a diagnosis of schizophreniform disorder at age of schizophreniform disorder at age 26 than controls.26 than controls. (Arseneault et al 2002) (Arseneault et al 2002)
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CannabisCannabis
No pre-No pre-existing existing
psychosispsychosis
Pre-existing Pre-existing psychosispsychosis
Psychosis outcomePsychosis outcome
Interaction with pre-existing Interaction with pre-existing psychosispsychosis
Interaction with pre-existing Interaction with pre-existing psychosispsychosis
T1T1
T3T3
2.2%2.2% 54.7%54.7%
American Journal of Epidemiology, 2002American Journal of Epidemiology, 2002
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ActionAction
EElimination of cannabis use would reduce the limination of cannabis use would reduce the incidence of schizophrenia by approximately incidence of schizophrenia by approximately 8% 8%
Discourage cannabis use in adolescence Discourage cannabis use in adolescence under the age of 18under the age of 18
Discourage cannabis use in adolescence with Discourage cannabis use in adolescence with +FH+FH
Discourage cannabis use in adolescence Discourage cannabis use in adolescence with schizotypal traits.with schizotypal traits.
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UrbanicityUrbanicity
IIndividuals who spent their first 15 years of ndividuals who spent their first 15 years of life in a highly urban area were nearly life in a highly urban area were nearly three three timestimes as likely to be diagnosed with as likely to be diagnosed with schizophrenia, compared with people who schizophrenia, compared with people who grew up in rural areas. grew up in rural areas. ((Pedersen CBPedersen CB and and Mortensen PBMortensen PB 2001) 2001)..
A A fifth to a thirdfifth to a third of individuals exposed to of individuals exposed to bothboth the the urban upbringing urban upbringing and the genetic and the genetic risk factors attract the disorder because of risk factors attract the disorder because of their coparticipation. their coparticipation. (van Os et al 2004)(van Os et al 2004)
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1 2 3 4 5
Ris
k sc
hizo
phre
nia
Am J Psychiatry, 2004Am J Psychiatry, 2004
DoDo genes enhance urban risk? genes enhance urban risk? (n=7076)(n=7076)
DoDo genes enhance urban risk? genes enhance urban risk? (n=7076)(n=7076)
FH+FH+
FH-FH-
Population Population densitydensity
χχ22=9.1, df=1, =9.1, df=1, PP=0.003=0.003
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ActionAction
Living outside a city before age 15 may Living outside a city before age 15 may reduce chances of getting reduce chances of getting schizophrenia schizophrenia
Avoid raising up children in dense urban Avoid raising up children in dense urban environment especially if FH +environment especially if FH +
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Dysfunctional familiesDysfunctional families
Risk of getting schizophrenia (for Risk of getting schizophrenia (for children genetically predisposed to children genetically predisposed to schizophrenia) can be up to schizophrenia) can be up to eight eight timestimes higher in high stress " higher in high stress "dysfunctionaldysfunctional familiesfamilies" vs. low stress " vs. low stress households households ((TienariTienari et al 2004) et al 2004)
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ActionAction
Attempt to keep stress levels in the Attempt to keep stress levels in the family environment at a relatively low family environment at a relatively low level. Learn how to manage stress well. level. Learn how to manage stress well. Stress InformationStress Information..
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Pregnancy InfectionsPregnancy Infections
MMothers who suffer from flu, viruses and others who suffer from flu, viruses and other infections during the other infections during the first trimester first trimester of of pregnancy are at significantly pregnancy are at significantly increased risk of schizophrenia - up to increased risk of schizophrenia - up to seven timesseven times higher than children who higher than children who are not exposed to flu/viruses during the are not exposed to flu/viruses during the first first trimestertrimester of pregnancy. of pregnancy. (Brown et al (Brown et al 2004)2004)
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ActionAction
BBecome pregnant only after (at least ecome pregnant only after (at least several weeks after) taking a several weeks after) taking a vaccination shot. Make extra efforts to vaccination shot. Make extra efforts to avoid exposure of mother to influenza avoid exposure of mother to influenza and other viruses during pregnancy. and other viruses during pregnancy.
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Obstetric ComplicationsObstetric Complications
RRisk for schizophrenia isk for schizophrenia isis fourfour times times higher for children who suffer from higher for children who suffer from hypoxia during childbirth hypoxia during childbirth (Dalman BJP (Dalman BJP 2001)2001)
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ActionAction
For reduced risk of children with For reduced risk of children with schizophrenia, mothers should make schizophrenia, mothers should make extra efforts to avoid any possible extra efforts to avoid any possible delivery complications and to be in the delivery complications and to be in the best possible hospital environment in best possible hospital environment in case complications do occurcase complications do occur..
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Paternal AgePaternal Age
Children born to fathers aged over 50 Children born to fathers aged over 50 could be as much as could be as much as four timesfour times more more likely to develop schizophrenia than likely to develop schizophrenia than those born to fathers aged 21 to those born to fathers aged 21 to 2424((Rasmussen Rasmussen et al 2004 BMJ)et al 2004 BMJ)
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ActionAction
For reduced risk of children with For reduced risk of children with schizophrenia, men schizophrenia, men may choose to may choose to have children while they are younger have children while they are younger (under 40) rather than older. (under 40) rather than older.
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PREVENTION upon indicators of developmental vulnerability
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: PredictionContinuity: Prediction
Hanssen, BakHanssen, Bak et al, 1998 et al, 1998
TT11
TT22
T3T3
±± 7000 7000
±± 5500 5500
±± 4700 4700
1 year1 year
2 years2 years
Psychotic symptomPsychotic symptom
Psychotic disorderPsychotic disorder
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CIDI ratings at T1 as independent predictors of being incident patient at T3
CIDI ratings at T1 as independent predictors of being incident patient at T3
HanssenHanssen et al, 2000 et al, 2000
3.1 2.1
5.2
11.1
0
2
4
6
8
10
12
OR
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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
PV(%) Treatment Success
Rate (%)
NNT NNI
5 25 80 79
5 50 40 39
20 25 20 19
20 50 10 9
50 25 8 7
50 50 4 3
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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
1. General population
Filter 1: Illness behaviour
2. Population attending GP
Filter 2: GP recognition
4. Mental health out-patients
Filter 4: Psychiatrist referral
3. GP recognised
Filter 3: GP referral
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ASPISASPIS (N = 2000)(N = 2000)
SCHIZOTYPYSCHIZOTYPY
COGNITIONCOGNITION
GENESGENES
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Endophenotypes for SchizophreniaEndophenotypes for Schizophrenia
Brain Structure Cognition
Schizotypy
GENES
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Candidate genes for Schizophrenia
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Effect of COMT genotype on Effect of COMT genotype on SSchizotypal chizotypal DDimensionsimensions
COMT GENOTYPECOMT GENOTYPE
VAL / VALVAL / VAL
DOPAMINE DOPAMINE
VAL / METVAL / MET
MET / METMET / MET
SCHIZOTYP. SCHIZOTYP. PHENOTYPEPHENOTYPE
POSITIVEPOSITIVE
NEGATIVENEGATIVE
DISORGANIZEDDISORGANIZED
PARANOIDPARANOID
Stefanis et al. 2004 Biol. Psychiatry
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COMT GENOTYPE EFFECT ON COMT GENOTYPE EFFECT ON NEGATIVE SCHIZOTYPY: ASPISNEGATIVE SCHIZOTYPY: ASPIS
Young conscripts Young conscripts (n=542) with lower (n=542) with lower level of dopamine level of dopamine transmission in PFC, transmission in PFC, score significantly score significantly higher on “negative” higher on “negative” schizotypal items, schizotypal items, related to social related to social isolation and isolation and indifference for social indifference for social contact.contact.
181249112N =
COMT GENOTYPE
val/valmet/valmet/met
SP
Q N
EG
ATIV
E S
CH
IZO
TYP
Y F
AC
TOR
Stefanis et al. 2004 Biol. Psychiatry
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DOPAMINE : Tuning Cognitive PerformanceDOPAMINE : Tuning Cognitive Performance
Low levels of Low levels of dopamine dopamine transmission in PFC transmission in PFC associated with associated with increased increased inconsistency of inconsistency of response (noise) response (noise) during cognitive tasks during cognitive tasks
177242109N =
COMT GENOTYPE
val/valmet/valmet/met
VARI
ABIL
ITY
OF R
ESPO
NSE(
CPT)
Stefanis et al. American Journal of Psychiatry (in press)
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