Prevention of schizophrenia

Introduction
In arguing for increased research funding, attention is often drawn to the finding that schizophrenia accounts for 2.3% of the total burden of disease (disability adjusted life years, DALYs) in established market economies (Murray and Lopez, 1996). How is it that, despite 1.4 - 2.8% of national health care being devoted to the direct costs of schizophrenia, the burden of disability is still so high? What would the burden of schizophrenia be if funds were unlimited and optimal treatments (medication, psychosocial interventions, service mix, etc.) were delivered consistently?

Most commentators would concede that the burden would still be inevitable. In other words, a substantial proportion of the DALYs associated with schizophrenia are ‘unavertable’ in terms of secondary and tertiary prevention. An alternative, and more ambitious, approach to averting DALYs is to reduce the incidence of a disorder. This section will discuss issues related to primary prevention in general and then speculate on directions for future research related to schizophrenia.

The science of prevention
In its simplest form, primary prevention aims to reduce the incidence of a disease.

Prevention strategies can be directed at different target populations (Gordon, 1983; Mrazek and Haggerty, 1994): (i) universal preventive interventions are aimed at the general population regardless of risk status/susceptibility status; (ii) selective preventive interventions target particular population subgroups, who may be more susceptible to a disorder but who are still symptom free; (iii) indicated prevention is targeted at individuals who have the early features or subclinical manifestations of a disorder.

Universal interventions have strengths and weakness that relate to the features of both the exposure (the risk-modifying variable, be it genetic, epigenetic or an interaction between the two) and the disorder. This approach alleviates the need to identify a minority of individuals who are ‘high-risk’  -  the focus of much current research in the prevention of schizophrenia. If we can identify such individuals, and if we can reduce their risk, then this is a highly desirable goal. However, if we cannot identify high-risk individuals, we need to consider alternative strategies.

Geoffrey Rose (1992) has emphasized that population-based interventions are best suited to risks that are distributed throughout the population, albeit not in equal measure. Those at high risk of disease, seemingly an obvious target for preventative action, may in fact be relatively rare. Those at medium risk may be more common and, therefore, may account for a much higher proportion of disease.

For example, if a large proportion of the community is exposed to a small risk, then population-based interventions may avert more illness (greater number of cases prevented) than interventions based on the rare, high-risk individuals. Rose (1992) then introduced the concept of the ‘prevention paradox’  -  a preventive measure that brings large benefits to the community but which offers little to the majority who are, themselves, at low risk. Indeed, the intervention may mean that such individuals have to give up something; hence the paradox. For example, many population-based interventions (e.g.  vaccination,  wearing a seatbelt)  bring little direct benefit to the individual, but individuals are willing to accept them because they cause little inconvenience. Inconvenience is weighed against the frequency of the undesirable outcome and its severity.

John McGrath
Queensland Centre for Schizophrenia Research, Wolston Park Hospital, Wacol, Australia

REFERENCES

  • Barker DJP (1992) Fetal and Infant Origins of Adult Disease. London: British Medical Journal.
  • Bebbington P, Wilkins S, Jones P et al. (1993) Life events and psychosis: initital results from the Camberwell Collaborative Psychosis Study. British Journal of Psychiatry 162, 72 - 79.
  • Bennedsen BE (1998) Adverse pregnancy outcome in schizophrenic women: occurence and risk factors. Schizophrenia Research 33, 1 - 26.
  • Brown AS, Susser ES, Butler PD, Richardson AR, Kaufmann CA, Gorman JM (1996) Neurobiological plausibility of prenatal nutritional deprivation as a risk factor for schizophrenia. Journal of Nervous and Mental Disease 184, 71 - 85.
  • Fatemi SH, Emamian ES, Kist D et al. (1999) Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Molecular Psychiatry 4, 145 - 154.
  • Gordon R (1983) An operational classification of disease prevention. Public Health Reports 98, 271 - 282.
  • Harrison G, Glazebrook C, Brewin J et al. (1997) Increased incidence of psychotic disorders in migrants from the Caribbean to the United Kingdom. Psychological Medicine 27, 799 - 806.
  • Hennekens CH, Buring JE (1987) Epidemiology in Medicine. Boston, MA: Little, Brown.
  • Hornig M, Weissenbock H, Horscroft N, Lipkin WI (1999) An infection-based model of neurodevelopmental damage. Proceedings of the National Academy of Sciences of the USA 96, 12102 - 12107.
  • Kraemer HC, Kazdin AE, Offord DR, Kkessler RC, Jensen PS, Kupfer DJ (1997) Coming to terms with the terms of risk. Archives of General Psychiatry 54, 337 - 343.
  • Kuller LH (1999) Circular epidemiology [see comments]. American Journal of Epidemiology 150, 897 - 903.
  • LaMantia A (1999) Forebrain induction, retinoic acid, and vulnerability to schizophrenia: insights from molecular and genetic analysis in developing mice. Biological Psychiatry 46, 19 - 30.
  • Last JM (1988) A Dictionary of Epidemiology. New York: Oxford University Press.
  • Lipska BK, Jaskiw GE, Weinberger DR (1993) Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology 9, 67 - 75.
  • Lucas A, Morley R, Cole TJ (1998) Randomised trial of early diet in preterm babies and later intelligence quotient. British Medical Journal 317, 1481 - 1487.
  • Mallard EC, Rehn A, Rees S, Tolcos M, Copolov D (1999) Ventriculomegaly and reduced hippocampal volume following intrauterine growth-restriction: implications for the aetiology of schizophrenia. Schizophrenia Research 40, 11 - 21.
  • Marcelis M, Navarro-Mateu F, Murray R, Selten J-P, van Os J (1998) Urbanization and psychosis:a study of 1942 - 1978 birth cohorts in the Netherlands. Psychological Medicine 28, 871 - 879.
  • McDonald C, Murray RM (2000) Early and late environmental risk factors for schizophrenia. Brain Research Reviews 31, 130 - 137.
  • McGorry PD, Jackson HJ (1999) The Recognition and Management of Early Psychosis: a Preventive Approach. Cambridge: Cambridge University Press.
  • McGrath JJ (1999) Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophrenia Research 40, 173 - 177.
  • McGrath J, Castle D (1995) Does influenza cause schizophrenia? A five year review. Australian and New Zealand Journal of Psychiatry 29, 23 - 31.
  • McGrath J, McGlashan TH (1999) Improving outcomes for recent-onset psychoses: disentangling hope, speculation and evidence. Acta Psychiatrica Scandinavica 100, 83 - 84.
  • McGrath JJ, Welham JL (1999) Season of birth and schizophrenia: a systematic review and metaanalysis of data from the Southern Hemisphere. Schizophrenia Research 35, 237 - 242.
  • Mednick SA, Schulsinger F, Venables PH (1981) The Mauritius Project. In: Prospective
  • Longitudinal Research: An Empirical Basis for the Primary Prevention of Psychosocial Disorders, Mednick SA, Baert A, eds. Oxford: Oxford University Press, pp. 314 - 316.
  • Mednick SA, Parnas J, Schulsinger F (1987) The Copenhagen High-Risk Project, 1962 - 86. Schizophrenia Bulletin 13, 485 - 495.
  • Mortensen PB (2000) Urban - rural differences in the risk for schizophrenia. International Journal of Mental Health 29, 101 - 110.
  • Mortensen PB, Pedersen CB, Westergaard T et al. (1999) Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340, 603 - 608.
  • Mrazek PJ, Haggerty RJ (1994) Reducing Risk for Mental Disorders: Frontiers for Preventive Intervention Research. Washington, DC: National Academic Press.
  • Murray CJ, Lopez AD (1996) The Global Burden of Disease. Boston, MA: Harvard School of Public Health.
  • Raine A, Venables PH, Mednick SA (1997) Low resting heart rate at age 3 years predisposes to aggression at age 11 years: evidence from the Mauritius Child Health Project. Journal of the American Academy of Child and Adolescent Psychiatry 36, 1457 - 1464.
  • Rantakallio P, Jones P, Moring J, von Wendt, L (1997) Associations between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: A 28- year follow-up. International Review of Epidemiology 26, 837 - 843.
  • Rose G (1992) The Strategy of Preventive Medicine. Oxford: Oxford University Press.
  • Sacker A, Done DJ, Crow TJ (1996) Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies. Psychological Medicine 26, 279 - 287.
  • Salvatore M, Morzunov S, Schwemmle M, Lipkin WI (1997) Borna disease virus in brains of North American and European people with schizophrenia and bipolar disorder. Bornavirus Study Group. Lancet 349, 1813 - 1814.
  • Sartorius N, Henderson AS (1992) The neglect of prevention in psychiatry. Australian and New Zealand Journal of Psychiatry 26, 550 - 553.
  • Schulsinger F, Parnas J, Mednick S, Teasdale TW, Schulsinger H (1987) Heredity - environment interaction and schizophrenia. Journal of Psychiatric Research 21, 431 - 436.
  • Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P (1994) Folic Acid Metabolism and Mechanisms of Neural Tube Defect. Chichester, UK: Wiley.
  • Susser E, Neugebauer R, Hoek H et al. (1996) Schizophrenia after prenatal famine: further evidence. Archives of General Psychiatry 53, 25 - 31.
  • Susser EB, Brown A, Matte TD (1999) Prenatal factors and adult mental and physical health. Canadian Journal of Psychiatry 44, 326 - 334.
  • Susser M (1991) What is a cause and how do we know one? A grammar for pragmatic epidemiology. American Journal of Epidemiology 133, 635 - 648.
  • Tarrant CJ, Jones PB (1999) Precursors to schizophrenia: do biological markers have specificity? Canadian Journal of Psychiatry 44, 335 - 349.
  • Tienari P, Wynne LC, Moring J et al. (1994) The Finnish Adoptive Family Study of schizophrenia. Implications for family research. British Journal of Psychiatry Suppl. 20 - 26.
  • Torrey EF, Miller J, Rawlings R, Yolken RH (1997) Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophrenia Research 28, 1 - 38.
  • Tsuang MT, Stone WS, Faraone SV (2000) Towards the prevention of schizophrenia. Biological Psychiatry 48, 349 - 356.
  • van Os J, Fahy TA, Bebbington P et al. (1994) The influence of life events on the subsequent course of psychotic illness. A prospective follow-up of the Camberwell Collaborative Psychosis Study. Psychological Medicine 24, 503 - 513.
  • Wahlbeck K, Forsen T, Osmond C, Barker DJ, Eriksson JG (2001) Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood. Archives of General Psychiatry 58, 48 - 52.
  • Welham J, McLachlan G, Davies G, McGrath J (2000) Heterogeneity in schizophrenia; mixture modelling of age-at-first-admission, gender and diagnosis. Acta Psychiatrica Scandinavica 101, 312 - 317.

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