Elsevier

The Lancet

Volume 361, Issue 9354, 25 January 2003, Pages 281-288
The Lancet

Articles
Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison

https://doi.org/10.1016/S0140-6736(03)12323-9Get rights and content

Summary

Background

Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis.

Methods

We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31%) had developed psychosis and 52 (69%) had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people.

Findings

In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum.

Interpretation

Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.

Introduction

Psychotic disorders involve striking disturbances of thought, perception, affect, and behaviour. The major psychotic disorders, especially schizophrenia and bipolar disorder, are relatively undifferentiated during the early phase of illness, so that to distinguish them at this stage can be difficult.1 However, studies done early in the course of psychosis are essential for an understanding of the neurobiology and treatment of these disorders.

Although increasing consensus exists that the structure of the brain is abnormal in major psychotic disorders, whether these abnormalities predate onset of illness and are relatively fixed over its course, or whether they are progressive, remains controversial.2 Results of neuroimaging studies suggest that abnormalities that are qualitatively similar to those evident in established schizophrenia and bipolar disorder are apparent in patients presenting with their first episode of psychosis3, 4, 5, 6 and in individuals without psychosis with a strong familial risk of schizophrenia.7 However, results of recent longitudinal neuroimaging studies in patients with schizophrenia have shown structural changes within the same patients over time, especially in the early stages of illness.8 These two sets of findings raise the possibility that neuroanatomical abnormalities seen in patients with psychotic disorders reflect a combination of pre-existing vulnerability and changes associated with the first expression of psychotic symptoms.

We aimed to investigate this model of psychosis with MRI, to assess people at ultra high-risk of development of psychosis before and after onset of their first episode of psychosis. On the basis of our own and other work, we predicted that ultra high-risk people would show volumetric abnormalities before they became psychotic, and that these would be qualitatively similar to those seen in patients with established schizophrenia and bipolar disorder.3, 4, 5, 6 A second prediction was that there would also be progressive loss of grey matter in the medial temporal cortex associated with development of psychosis in ultra high-risk indviduals. This hypothesis was based on findings of smaller medial temporal volumes in patients with psychosis than in ultra high-risk individuals.7, 9

Section snippets

Participants

We recruited people at ultra high-risk of development of psychosis from the personal assessment and crisis evaluation (PACE) clinic in Melbourne, Australia, which manages young people at risk of this disorder.10 We used a close-in strategy to identify individuals at ultra high-risk of psychosis with a combination of trait and state factors (panel).10 This strategy identified people whose theoretical risk of becoming psychotic was 41% within a 12-month period.10 We enrolled all individuals at

Results

We enrolled 75 people for the cross-sectional comparison. All participants were aged 14–30 years and had never had an episode of frank psychosis. Of these, 23 (31%) developed psychosis during follow-up, 18 within 12 months and a further five within 24 months. The remaining 52 (69%) did not develop psychosis during the follow-up period. Follow-up was for at least 12 months: 67 (89%) people were reassessed between 12 and 18 months; maximum follow-up was 44 months. The groups did not differ by

Discussion

Cross-sectional comparison of people at ultra high-risk for development of psychosis showed striking differences in regional grey-matter volume between those who subsequently developed a psychotic illness and those who did not, even though these subgroups were clinically indistinguishable at the time of scanning. Thus, in this high-risk sample, smaller volumes of grey matter in the right prefrontal cortex, insular, and temporal cortex, the right basal ganglia, and the cingulate cortex

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