Machine learning and brain imaging in psychosis

Abstract

Over the past years early detection and intervention in schizophrenia have become a major objective in psychiatry. Early intervention strategies are intended to identify and treat psychosis prior to fulfilling diagnostic criteria for the disorder. To this aim, reliable early diagnostic biomarkers are needed in order to identify a high-risk state for psychosis and also predict transition to frank psychosis in those high-risk individuals destined to develop the disorder. Recently, machine learning methods have been successfully applied in the diagnostic classification of schizophrenia and in predicting transition to psychosis at an individual level based on magnetic resonance imaging (MRI) data and also neurocognitive variables. This work investigates the application of machine learning methods for the early identification of schizophrenia in subjects at high risk for developing the disorder. The dataset used in this work involves data from the Edinburgh High Risk Study (EHRS), which examined individuals at a heightened risk for developing schizophrenia for familial reasons, and the FePsy (Fruherkennung von Psychosen) study that was conducted in Basel and involves subjects at a clinical high-risk state for psychosis. The overriding aim of this thesis was to use machine learning, and specifically Support Vector Machine (SVM), in order to identify predictors of transition to psychosis in high-risk individuals, using baseline structural MRI data. There are three aims pertaining to this main one. (i) Firstly, our aim was to examine the feasibility of distinguishing at baseline those individuals who later developed schizophrenia from those who did not, yet had psychotic symptoms using SVM and baseline data from the EHRS study. (ii) Secondly, we intended to examine if our classification approach could generalize to clinical high-risk cohorts, using neuroanatomical data from the FePsy study. (iii) In a more exploratory context, we have also examined the diagnostic performance of our classifier by pooling the two datasets together. With regards to the first aim, our findings suggest that the early prediction of schizophrenia is feasible using a MRI-based linear SVM classifier operating at the single-subject level. Additionally, we have shown that the combination of baseline neuroanatomical data with measures of neurocognitive functioning and schizotypal cognition can improve predictive performance. The application of our pattern classification approach to baseline structural MRI data from the FePsy study highly replicated our previous findings. Our classification method identified spatially distributed networks that discriminate at baseline between subjects that later developed schizophrenia and other related psychoses and those that did not. Finally, a preliminary classification analysis using pooled datasets from the EHRS and the FePsy study supports the existence of a neuroanatomical pattern that differentiates between groups of high-risk subjects that develop psychosis against those who do not across research sites and despite any between-sites differences. Taken together, our findings suggest that machine learning is capable of distinguishing between cohorts of high risk subjects that later convert to psychosis and those that do not based on patterns of structural abnormalities that are present before disease onset. Our findings have some clinical implications in that machine learning-based approaches could advise or complement clinical decision-making in early intervention strategies in schizophrenia and related psychoses. Future work will be, however, required to tackle issues of reproducibility of early diagnostic biomarkers across research sites, where different assessment criteria and imaging equipment and protocols are used. In addition, future projects may also examine the diagnostic and prognostic value of multimodal neuroimaging data, possibly combined with other clinical, neurocognitive, genetic information.