Predicting schizophrenia: findings from the Edinburgh High-Risk Study
Johnstone EC, Ebmeier KP, Miller P, Owens DG and Lawrie SM;
Commented by , 28 Feb 2005
Aim
It is well know that genetic factors play an important role in the etiology of schizophrenia. For example, 50% of the siblings of monozygotic twins will also be affected by this serious disorder.
However, to date it is not yet possible to predict which people at risk will finally develop the disorder. The article describes of the Edinburgh High-Risk Study in people at risk for schizophrenia, a major study in this area that was started in 1994. Its aim is to examine which individuals with a genetically determined high risk for schizophrenia finally develop schizophrenia and which do not.
Methods
The authors examined 163 young people aged 16-24 years who did not have a history of schizophrenia and who had at least two first- or second-degree relatives with schizophrenia. In such a population it was estimated that 10-15% would develop schizophrenia within 10 years.
These people were compared with a control group of 36 individuals. The participants were followed up for ten years with psychopathological assessments, magnetic resonance imaging and a neuropsychological test battery. It was assessed which baseline characteristics distinguished between high-risk individuals who did develop schizophrenia, those who did not develop schizophrenia - with or without isolated psychotic symptoms - and a healthy control group.
Furthermore, characteristics of the high-risk participants who became ill with schizophrenia should be described.
Results
While 20 people of those at risk fell will with schizophrenia within 2(1/2) years, many more subjects experienced isolated or partial psychotic symptoms. The factors that differentiated the participants who developed schizophrenia from those who did were related to schizotypal features – e.g. social anxiety and withdrawal.
Furthermore, a number of psychological tests, measures of childhood behaviour, developmental measures of ocular hypertelorism and dermatoglyphic variables, and left thalamic volume showed between groups differences.
Discussion
The authors must be lauded for conducting such a difficult study with a long follow-up of 10 years. There are some limitations that need to be discussed: It cannot be ruled out with absolute certainty whether the individuals who later developed schizophrenia were in the prodromal phase of the illness at baseline, because about half of those who fell ill had "psychotic or possibly psychotic symptoms" on entry to the study.
Furthermore, some of those who were well at the end of the study may still develop psychosis later in life. The control group may not have been ideal because they were volunteers partly selected by their willingness to continue with this ongoing study.
The main implications of the study are that importantly many more participants showed psychotic symptoms but did not fulfil the criteria for schizophrenia. Thus, only looking at those patients who finally develop the full-blown disorder is a oversimplification.
Furthermore, it may be possible to predict those of a high-risk group who will develop schizophrenia using simple measures of schizotypal features. These psychopathological instruments were better predictors than more complicated biological measures such as MRI.