Schizophrenia risk factors and causes

In order to develop a framework for primary prevention, it is important to understand terminology surrounding risk factors and causes (Susser, 1991; Kraemer et al., 1997). A risk factor can be anything that is, statistically, associated with disease.

As such, risk factors may point us towards causes but are not necessarily involved in producing an outcome or disease. Variables that correlate with outcomes but do not precede them should not be labelled risk factors, but rather sequelae, consequences or concomitants. When considering risk factors, it is also important to understand that there are risk indicators that can be epiphenomena or proxy markers of an underlying risk-modifying factor that is closely allied with cause. A major problem with a brain disease like schizophrenia is that the current knowledge base is limited and, therefore, we cannot confidently predict if a risk factor is causally related or whether it is a proxy marker.

As a result, the term 'risk-modifying factor' should be reserved for factors that appear to operate within the causal chain (contribute to the outcome). If factors that truly modify risk could be reduced, then so should the incidence of the resultant disorder. In neurodevelopmental models of schizophrenia, we are looking for distal or 'upstream' risk-modifying variables. Also, these factors may operate directly or indirectly (sometimes referred to as first- or second-order effects). Risk-modifying factors can be fixed (e.g. sex) or variable (drug abuse). They can, of course, also be protective or adverse.

In order to reduce the incidence of schizophrenia, we need to identify candidate risk-modifying variables that can themselves be modified. Ideally, the interventions should have a number of characteristics. They should be effective, in that they should reduce or eliminate the risk-modifying variable. They must be safe and acceptable to the community or susceptible individual. This involves the balance of risk and benefit, together with convenience. Finally, they must be cost effective and, ideally, cheap, especially if applied universally.

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Barriers to the primary prevention of schizophrenia

A major factor that has eroded confidence in primary prevention of schizophrenia has been a perception that we have made little progress in our understanding of the aetiology of conditions of this type. We know about many risk factors but cannot yet identify those that are powerful modifiers of risk except, perhaps, genetic influences, which we do not yet understand. The slow progress has engendered a feeling of nihilistic despair. The other factor that has hindered progress is the debate about when to start primary prevention research. Should we wait until every minute detail about aetiology and pathogenesis is unravelled before primary prevention attempts are made, or should we trust inconclusive but suggestive data? In the past, there have been some spectacular applications of primary prevention, based on either incorrect or incomplete assumptions. The miasma theory of ill health (that brackish, impure water and soil gave off noxious emanations) led to the call for improved sanitation long before microorganisms were suspected or discovered.