or even for years as the only premonitory signs of an immi- nent mental disorderâ. The first systematic analyses of the prodrome of schizophrenia were conducted ...
SPECIAL ARTICLE
Early detection of schizophrenia: current evidence and future perspectives HEINZ HÄFNER, KURT MAURER Schizophrenia Research Unit, Central Institute of Mental Health, J5, D-68159 Mannheim, Germany
Research into the early course of schizophrenia has identified a prepsychotic prodromal stage (mean duration: 4.8 years) and a psychotic prephase (mean duration: 1.3 years). Comparisons of individually matched samples have demonstrated prodromal symptoms common to schizophrenia and moderate to severe depression. It is not until positive symptoms emerge that psychosis and mood disorders become distinguishable from each other. In both disorders the prodromal stage early produces functional impairment and related social consequences. Hence, early intervention is of great public health relevance. This intervention is targeted at manifest symptoms and not at the underlying, still unknown disease process. Cognitive-behavioural therapy at the prepsychotic prodromal stage seems to favourably influence the short-term illness course. In the psychotic prephase, a combination with low-dose antipsychotics seems to have some efficacy. The aim of early recognition by the instruments discussed in this paper is to permit the identification of the largest possible proportion of at-risk persons as early as possible and their referral to appropriate treatment. Key words: Schizophrenia, prodromal symptoms, depression, early recognition, early intervention
In the last two decades, widespread attention has been accorded to the insight that, in psychosis, the first contact with mental health services is frequently preceded by a period of evolving disorder whose duration is of several years (1-5). Early recognition and early intervention have fanned hopes of preventing or postponing psychosis onset, reducing severity of illness or at least ameliorating the personal and social consequences involved. In the wake of the pioneering work of McGorry and his Melbournebased group, early recognition and intervention centres for psychosis have sprung up in many countries (6). Kraepelin (7) already described “minor changes in mood, which may be recurrent or persist for weeks, months or even for years as the only premonitory signs of an imminent mental disorder”. The first systematic analyses of the prodrome of schizophrenia were conducted by Sullivan (8) and Cameron (9,10), with the aim of initiating early intervention, but these attempts failed. After World War II, Conrad (11) and Docherty et al (12) proposed stage models of evolving illness, but these models could not be adequately replicated (13) and failed to offer an opportunity for developing effective approaches to early intervention. In the past two decades, a series of instruments for the early recognition of schizophrenia have been developed. Their aim was the identification of persons at a high enough risk for psychosis to permit diagnostic discrimination and justify early intervention. Because populationbased prospective studies of onset and early illness course are impractical, due to the low incidence rate of schizophrenia and the high frequency of an uncharacteristic type of onset, these instruments were developed on the basis of retrospective studies. The psychopathological phenomena that can be used for early diagnostic discrimination and/or for predicting the onset of a psychotic episode in practice include: a) characteristic prodromal signs and symptoms; b) neuropsychological deficits assessed in cognitive tests (14); c) characteristics of the illness course. 130
Potent biological markers that would facilitate the early recognition of psychotic disorders are not yet available. In the Edinburgh high-risk study (15) and the Melbournebased early-intervention programme (16), high-risk probands who transited to psychosis showed a significant volume reduction in the hippocampus-parahippocampus area in comparisons with high-risk probands without transition to psychosis. This finding of high theoretical interest, however, cannot yet be harnessed in practice.
RECONSTRUCTING THE EARLY COURSE OF SCHIZOPHRENIA AND ITS CONSEQUENCES In the ABC Schizophrenia Study (3), we studied a population-based sample of 232 patients with a first episode of schizophrenia spectrum disorder (ICD-9: 295, 297, 298.2, 298.4), aged 12 to 59 years, compared with age- and sexmatched healthy individuals from the study area. The patients were assessed using the Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses (IRAOS) (17). On the basis of these data, we defined two stages in the early illness course, which have implications for risk identification and intervention: a) a prepsychotic prodromal stage, from the first sign of illness until the first psychotic symptom, with a mean duration of 4.8 years (median 2.33); b) a psychotic prephase, from the first positive symptom until first admission, with a mean duration of 1.3 years (median: 0.8 years), 1.1 years until the climax of the first episode plus 2 further months until first admission. Lower medians than means reflect a preponderance of shorter durations. Eighteen percent of the cases had an acute type of onset of four weeks or less, 15% a subacute type of four weeks to one year, and 68% a chronic type of one year or more. Only 6.5% of onsets occurred with positive symptoms alone (18). Table 1 gives an overview of selected studies on the World Psychiatry 5:3 - October 2006
Table 1 Mean duration of the prephase of schizophrenia from onset (first sign, first psychotic symptom) until first contact or first admission in selected studies (modified from 26) Authors
N
Duration from first sign (years)
Gross (1) (Germany, 1969)
290
3.5
Lindelius (19) (Sweden, 1970)
237
Huber et al (2) (Germany, 1979)
502
Loebel et al (20) (USA, 1992)
70
Beiser et al (21) (Canada, 1993)
70
McGorry et al (4) (Australia, 1996) Lewine (22) (USA, 1980) Häfner et al (3) (Germany, 1995) Johannessen et al (23) (Norway, 1999) Ho et al (24) (USA, 2003) Köhn et al (25) (Germany, 2003)
200
4.4 3.3 2.9 2.1 2.1
97 232
1.0 1.0 1.4 1.9
4.8
43 156
Duration from first psychotic symptom (years)
1.1 2.2
2.7
1.4
5.9
duration of untreated illness (DUI) and/or untreated psychosis (DUP). Results on DUI differ more markedly, because of the difficulty of precisely defining illness onset and the lack of suitable assessment instruments in a majority of studies. In about three-quarters of cases, schizophrenia onset occurs with slowly mounting depressive and negative symptoms involving increasing functional impairment and cognitive dysfunction (27). DUP, assessed in a great number of studies, depends on the conspicuousness and velocity of symptom accumulation, help-seeking behaviour and the availability of appropriate mental health services (28-30). DUP can be shortened by improving the last two factors. An awareness programme educating and alerting both the population and health services of a region in Norway presumably helped to reduce DUP from 2.5 years to 0.5 years (31). In a majority of studies, a prolonged DUP turned out to be a predictor of an unfavourable illness course (4,20,3236). It was associated with a more severe course of the first episode and all the consequences associated with the latter (e.g., greater risks, more inpatient days, higher costs) (35-37). A small number of studies have also reported sustained neuropsychological deficits, higher scores on negative symptoms and disorganization, and an unfavourable functional outcome (38-40). It is still an unsettled question whether a prolonged DUP is also associated with more psychotic relapses, as reported by several authors (32,41), because long-term follow-ups are rare.
Table 2 The ten most frequent earliest signs of schizophrenia (independent of the course) reported by the patients (modified from 3) % Total (n = 232)
% Men (n = 108)
% Women (n = 124)
Restlessness
19
15
22*
Depression
19
15
22*
Anxiety
18
17
19*
Trouble with thinking and concentration
16
19
14* 20*
Worrying
15
19
Lack of self-confidence
13
10
15*
Lack of energy, slowness
12
18
15*
Poor work performance
11
12
10*
Social withdrawal, distrust
10
18
12*
Social withdrawal, communication
10
18
12*
*Significantly more frequent in females, p
