NEW STRATEGIES IN THE PREVENTION AND TREATMENT OF SCHIZOPHRENIA III

Reducing Risk of Getting Schizophrenia 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)  Interaction with pre-existing psychosis Cannabis T1 No preexisting psychosis Pre-existing psychosis 2.2% T3 Psychosis outcome 54.7% American Journal of Epidemiology, 2002 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.    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) Do genes enhance urban risk? (n=7076) 12 Risk schizophrenia 10 8 6 4 2 0 FH+ χ2=9.1, df=1, P=0.003 FH1 2 3 4 5 Population density Am J Psychiatry, 2004 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 +  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) Action  Attempt to keep stress levels in the family environment at a relatively low level. Learn how to manage stress well. Stress Information. 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) 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. Obstetric Complications  Risk for schizophrenia is four times higher for children who suffer from hypoxia during childbirth (Dalman BJP 2001) 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. 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) Action  For reduced risk of children with schizophrenia, men may choose to have children while they are younger (under 40) rather than older. 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.  Prepsychotic Expression of Illness Continuity: Prediction Psychotic symptom T1 ± 7000 1 year T2 Psychotic disorder ± 5500 2 years T3 ± 4700 Hanssen, Bak et al, 1998 CIDI ratings at T1 as independent predictors of being incident patient at T3 12 10 8 OR 6 4 2 0 11.1 5.2 3.1 2.1 ar va ib nd le co N Se ot Po re ss Tr ue y nt le Hanssen et al, 2000 The number of people screening positive for subclinical psychotic experiences who needed to be treated to prevent one case of full-blown psychotic disorder PV(%) Treatment Success Rate (%) NNT NNI 5 5 20 20 50 50 25 50 25 50 25 50 80 40 20 10 8 4 79 39 19 9 7 3 • 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 %. Making schizophrenia more predictable but for fewer patients 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% Predictors of schizophrenia dividing the „high risk ill‟ group from other high-risk participants Johnstone et al 2004 BJP Filter model of psychotic symptoms and psychotic disorder Filter 4: Psychiatrist referral Filter 3: GP referral 5. Psychiatric hospital 4. Mental health outpatients Filter 2: GP recognition Filter 1: Illness behaviour 3. GP recognised 2. Population attending GP 1. General population ASPIS (N = 2000)    SCHIZOTYPY COGNITION GENES Endophenotypes for Schizophrenia Schizotypy GENES Brain Structure Cognition Candidate genes for Schizophrenia Effect of COMT genotype on Schizotypal Dimensions COMT GENOTYPE  SCHIZOTYP. PHENOTYPE   VAL / VAL DOPAMINE POSITIVE NEGATIVE DISORGANIZED PARANOID   VAL / MET  MET / MET  Stefanis et al. 2004 Biol. Psychiatry COMT GENOTYPE EFFECT ON NEGATIVE SCHIZOTYPY: ASPIS  N= 112 249 181 met /met met /val val/val COMT GENOTYPE Young conscripts (n=542) 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 DOPAMINE : Tuning Cognitive Performance  Low levels of dopamine transmission in PFC associated with increased inconsistency of response (noise) during cognitive tasks N= 109 242 177 met /met met /val val/val COMT GENOTYPE Stefanis et al. American Journal of Psychiatry (in press)