Century of Schizophrenia is Enough

Jane Kelly1 and Robin M. Murray1

As Charles Pull's comprehensive review indicates, after a hundred years of investigation, schizophrenia remains a chronically unsatisfactory disease. Even as he outlines the supposed strengths of the concept, Prof. Pull reminds us that there are no pathognomonic symptoms of schizophrenia and that those individuals who receive the diagnosis have very different characteristics and widely varying outcome. Although Prof. Pull indicates that the use of standardized interviews and operational definitions enables trained clinicians to make the diagnosis reliably, there now exists a ''Tower of Babel'' of different operational definitions, some of which, such as the DSM criteria, are modified with confusing regularity. Consequently, the number of individuals diagnosed as schizophrenic varies by a factor of three depending on which definition is used [1]. The borders of some definitions are quite arbitrary; for example, according to ICD-10, if an illness lasts for 29 days, it is not schizophrenia, if it lasts for 32 days then it is schizophrenia. Most importantly, there is no sharp boundary between the phenomena of schizophrenia and manic-depressive psychosis; indeed, so many patients fall between the two psychotic categories, that an intermediate form, the so-called schizoaffective psychosis, had to be invented.

It has become increasingly clear that there is overlap in genetic predisposition to schizophrenia and affective psychosis [2-4]. Pull also notes that abnormalities in biological markers such as eye tracking and event-related potentials are found in other psychotic conditions. Furthermore, the meta-analysis of Elkis et al [5] has shown that lateral ventricular enlargement, the most consistent abnormality in those diagnosed as schizophrenic, is also found in affective psychosis. The fact that neither genetic predisposition nor biological abnormalities are specific for schizophrenia undermines the Kraepelinian concept of schizophrenia as a discrete disease entity.

In our view, therefore, 100 years of schizophrenia is enough. But what should we replace it with? Murray et al [6] pointed to the evidence that a number of developmental risk factors have been established for early-onset psychosis. These include obstetric complications and late winter/spring birth [7], as well as psychomotor and speech delay, inability to play and poorer cognitive performance [8]. Other patients, conventionally diagnosed as schizophrenic, have no developmental risk factors, often have symptoms of, or relatives with, affective disorder, and many become ill following social adversity. Murray et al [6] sought to divide the traditional category of schizophrenia into neurodevelopmental (or congenital) and adult-onset

1Institute of Psychiatry, Maudsley Hospital, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

cases; the latter had much in common with affective psychosis. This proposal deliberately harks back to views which were commonplace 100 years ago [9], but were displaced by the stultifying disease concept of dementia praecox/schizophrenia.

The existence of a neurodevelopmental form of psychosis received further support from latent class analyses [10,11], and from a twin study [12]. However, the neurodevelopmental adult-onset distinction has similar/difficulty to the Kraepelinian system in dealing with cases on the borders between the categories; that is, some psychotic patients appear to have both neurodevel-opmental impairment and socially reactive/affective characteristics. Furthermore, it has become clear that neurodevelopmental risk factors are not specific to schizophrenia. Thus, obstetric complications [7], childhood impairments [13] and cerebral ventricle enlargement [5] are also risk factors for affective psychosis, although the effect size is not so great as for schizophrenia.

A more plausible ''dimensional'' version of this idea is that there exists a spectrum of psychosis which is under the influence of two major aetio-logical effects. The first, ''neurodevelopmental impairment'', operates across psychosis but has maximal effect in chronic cases with an early onset and poor outcome. Such cases tend to be male and have a history of obstetric complications or of a family member with a similar illness; they are likely to have shown poor childhood function and to have structural brain abnormalities. The second effect arises when ''social adversity'' acts on genetic predisposition to affective psychosis to produce an acute psychosis. The effect of this factor is maximal at the acute onset—good outcome pole of psychosis; such cases tend to have good premorbid function and to be female, and generally show less evidence of structural brain abnormality. Thus, at the extreme poles of a continuum of psychosis, neurodevelopmental and social/affective aetiologies predominate respectively; however, in many of the intervening cases, both aetiological factors are operating.

Might a classification based on such dimensional concepts have more biological validity than the Kraepelinian system? A number of factor analytical studies of the symptoms shown by psychotic patients have produced three psychotic dimensions or syndromes (positive, negative, and disorganization) and two affective syndromes (mania and depression). Sham et al [14] showed that the positive and negative syndromes had pronounced, but different, developmental antecedents, while mania and depression did not; disorganization appeared to be a hybrid, being predicted by the combination of low IQ and a family history of mania.

One of the main purposes of classification is to predict outcome. How would a dimensional classification system work in this regard? Van Os et al [15], who studied the clinical characteristics of some 700 chronic psychotic patients, found that a four-dimensional model (positive, negative, manic and depressive dimensions) best fitted the data. They then compared the ability of dimensional and categorical representations of the patients' psychopathology to predict outcome; the dimensional approach had greater predictive power than conventional diagnostic categories.

In summary, we agree with Charles Pull that neither symptoms nor biological markers are specific to schizophrenia. While Pull looks to a day when more specific markers for schizophrenia will validate the concept and facilitate its diagnosis, we consider that this is an illusion. We are more impressed by the evidence that not only biological markers but also risk factors for psychosis operate across diagnostic categories. Indeed, not only are dimensions more closely related to risk factors than categories, but dimensions are also more useful in predicting outcome of psychosis. In short, psychotic patients should be distinguished by differences of degree rather than of kind, as a function of overlapping dimensions of psychopathology [16]. Professor Pull's article is a valiant eulogy for a concept which should be buried with the twentieth century.

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