When once is not enough: the case for repeated biopsychosocial assessments in psychosis

Although many clinicians still hold the Kraepelinian view of schizophrenia as an almost inevitably chronic and debilitating disease, many have moved to accepting schizophrenia (and psychoses in general) as a heterogeneous disorder with multiple possible courses and outcomes. This was also recently suggested by our 10-year follow-up of a large, epidemiological cohort of individuals first seen at the onset of any psychotic disorder (Morgan et al. 2014). In this cohort, we found that 46% of the subjects had remained free of psychotic symptoms for at least 2 years prior to follow-up, and this included 39.7% of those with a non-affective psychosis. Furthermore, we found that only 23% did not experience any remission during follow-up. If the course is so heterogeneous, why should we expect to understand the neurobiology of it by studying only one, or even two, predefined time points? If we applied this approach to other conditions, such as for example recurring and remitting multiple sclerosis, would we know more about the neurobiology of this disorder? Of course, the answer is no, since the biology, as the symptoms, fluctuates in time. Still, we seem to have had the expectation that by studying psychoses at one time point, and by simply moving to evaluating earlier stages, we could understand more about what is really happening in the biological systems of individuals with these disorders. When we have tried to study multiple time points, we have simply studied predefined, fixed points in time, in isolation. One of the consequences has been the view that schizophrenia is a progressive disorder. Zipursky et al. (2013) recently published a provoking editorial in which they argue against this view. They support this position by discussing evidence that schizophrenia does not present with the progressive loss of function typical of deteriorating conditions, nor with cognitive loss, and also that some of the brain changes observed in longitudinal studies could be due to external factors. So, could schizophrenia be a fluctuating disorder, and if so, what are the factors that might affect what we see? In reality, we know very little about what happens in between evaluations. The two editorials in this issue of EPS contribute to this debate providing two complementary and intriguing perspectives and some very important pointers for the direction to follow in research on the neurobiological basis of psychosis. The Editorial by Cropley & Pantelis (2014) discusses how, despite three decades of research, neuroimaging has actually contributed relatively little to our understanding of the pathophysiology of schizophrenia and is yet to have a clinical application. They propose that one of the main factors responsible for this has been the use of single assessments, which by providing a simple snapshot in time, ignore the importance of the trajectory of change. They start by discussing evidence from imaging studies on normal development and childhood-onset schizophrenia, which have provided evidence that brain regions develop in a non-linear fashion. As an example, they quote evidence that in childhood-onset schizophrenia, the normal parietofrontal pattern of progressive grey matter loss is more severe, but post-adolescence the grey matter loss slows down, becoming localised to prefrontal and temporal cortices. They then move to discussing studies of illness onset and the prodrome, which again suggest that these stages are characterised by active brain changes and again in a non-linear fashion. The authors argue that to understand these potential non-linear patterns of brain change, which could arise at different illness stages, and more importantly, in relation to concurrent symptoms, a re-conceptualisation of neuroimaging designs is required. Based on evidence that brain changes may fluctuate with changes in clinical state, they propose that frequent imaging assessments are needed to model the complex trajectories that occur with acute symptom changes. The authors propose that longitudinal designs in relation to changes in clinical status be employed to investigate neuroimaging markers of psychosis relapse. We shall also add that as well as being longitudinal in design, these neuroimaging studies should aim to evaluate large, epidemiologically representative samples of people suffering from *Address for correspondence: Dr P. Dazzan, Department of Psychosis Studies, PO40, Institute of Psychiatry, King’s College London, De Crespigny Park, London SE5 8AF, UK. (Email: paola.dazzan@kcl.ac.uk) Epidemiology and Psychiatric Sciences (2014), 23, 211–213. © Cambridge University Press 2014 doi:10.1017/S2045796014000328 EDITORIALS IN THIS ISSUE, SEPTEMBER 2014