Does a Shortened DUP Lead to a More Favourable Illness Course and Better Outcome

This important question stems from a hope of reducing the adverse consequences of the disorder by shortening the untreated early illness period. But objections have been raised against the implied causal association: ''is the link due to a common underlying factor, such as a more severe form of the illness with functional impairment after an insidious onset, more negative symptoms, more paranoid ideation?'' [74]. At any rate, it has been known since Kraepelin's days that an insidious onset with a long prodromal phase featuring negative symptoms and impairments is a clinical indicator of a poor illness course. In contrast, a highly acute onset without a prodromal stage seems to be associated with a favourable illness course as an intrinsic factor of the disease process. Verdoux et al. [95] have shown that demographic and clinical factors that predict a poor prognosis may also be associated with delayed presentation to psychiatric services.

Evidence for the assumption that shortening the early illness stages (DUP, DUI) ameliorates the further illness course could only be obtained in randomized controlled intervention studies among patients at early stages of their illness. Because of the unresolved problems posed by early recognition and reliably predicting psychosis risk, the studies were based on conventional definitions of high psychosis risk. The study conducted by McGorry et al. [70], which was based on 59 ultra-high-risk (UHR) probands, showed that, after one year of targeted cognitive behavioural therapy and low doses (on average 1.3 mg pro die) of risperidone, 7.1% of the fully compliant patients transited to psychosis, compared with 29.4% of the not fully compliant index cases and 35.7% of the controls, who had received unspecific therapy. Lewis et al. [96], in a study in which high-risk probands at the prodromal stage received cognitive behavioural therapy and social support, also found significant differences in outcome between the index cases and controls.

Table 1.3 Changes in brain morphology at the prodromal stage of schizophrenia according to selected studies

Brain

Before or at first

Study

Subjects

imaging

psychotic episode

At follow-up

Johnstone 162 psychotic risk;

MRI

High-risk subjects:

High-risk subjects

et al. [89]

18.1% psychotic

reduced

show reductions

Lawrie

(11.6%

hippocampal and

in temporal lobe

et al. [90]

schizophrenia),

thalamic volumes,

volumes; with

33% partly psychotic

changes occur

approaching

Risk period: 6 years

before psychosis

psychosis

anomalies

increase

Hoff

50 first episode

MRI volumetry

First episode:

No significant

et al. [71]

schizophrenics

structural

correlation of

25 controls

anomalies

DUP with

severity of

either cognitive

or structural

brain deficits

Fannon

37 first-episode

MRI

First episode:

No association

et al. [91]

schizophrenics

smaller brain

between DUP

Risk period: 1 year

volumes and

and any changes

cortical grey matter

volumes and larger

lateral and third

ventricle

Ho

156 DSM-IV

MRI grey and

First episode: no

No association

et al. [20]

schizophrenia

white

association between

between DUP

Risk period: 2 years

volumetric

DUP and volumetric

and MRI

(1 episode)

and surface

measures of the

anomalies

anatomy

brain

measurement

Pantelis

75 ultra-high-risk

MRI volumetry

High-risk cases:

Psychotic cases:

et al. [92]

(UHR) cases;

brain changes

reduction in

31% psychotic

appear before

grey matter

Risk period: 1 year

psychosis and

volume and left

further changes

caudate and

occur

hippocampus

Copolov

32 first episodes

MRI volumetry

High-risk subjects:

15 of 39 psychotic:

et al. [93]

with

hippocampus

hippocampus

no progression

schizophrenia;

*10% volume

of hippocampus

39 UHR cases

reduction

reduction

Risk period: 1 year

Malla

114 first episodes

CT

First episode: modest

Chronic cases:

et al. [94]

(schizophrenia or

enlargement of

sylvian fissure

schizophreniform)

sylvian fissure

significantly

and ventricle; no

larger

association with

DUP

CT, computed tomography; DUP, duration of untreated psychosis; UHR, ultra high risk.

CT, computed tomography; DUP, duration of untreated psychosis; UHR, ultra high risk.

Hence, appropriate early intervention administered to high-risk individuals from the late prepsychotic stage onwards can succeed in delaying the onset of a psychotic episode. This effect is analogous to that in relapse prevention in schizophrenia. But will early intervention also help to reduce negative symptoms and functional impairment enduringly?

In view of the independent courses of the negative-impairment dimension and the positive-symptom dimension over time, shortening the prodromal stage characterized by negative symptoms or DUI as a whole seems more promising than reducing the purely positive symptoms. In this context it should be kept in mind, as mentioned above, that in the first psychotic episode unspecific and negative symptoms also increase simultaneously with positive symptoms [18]. The aim of early intervention is not only to reduce the most enduring component of the illness, but also to try to reduce or even prevent the early social consequences, which decisively codetermine the social course of the disorder and the kind of life patients will be able to lead. This is why diagnostic recognition and prediction of schizophrenia as early as the prodromal stage are so important.

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Letting Go, Moving On

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