The RCPsych Article of the Month for July is ‘Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study‘ and the blog is written by authors Rafael Romero-García and Manuel Canal-Rivero and the article is published in The British Journal of Psychiatry

We are honoured that our paper “Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up” has been chosen as RCPsych Article of the Month.

During recent years, our team has been part of the “Programa de Atención a Fases Iniciales de Psicosis (PAFIP)”. PAFIP is a three-year early intervention initiative designed for individuals who have experienced their first episode of psychosis (FEP). Those who willingly joined this program received comprehensive care from a team of professionals, including psychiatric nursing, psychology, psychiatry, and social work. A decade after the onset of psychotic disorders, the PAFIP team reconnected with the participants for a follow-up evaluation.

A key question in schizophrenia research is, What should be considered negative symptoms? To answer this, we used a latent factor approach. These analyses allow us to determine to what extent individual items of the scales that measure negative symptomatology are measuring something in common. Through the design and implementation of PAFIP we had the opportunity to use Exploratory and Confirmatory Factor Analysis at different time points, improving the reliability of resulting factors.  Our analysis revealed that the individual items comprising The Scale for the Assessment of Negative Symptoms could be grouped into two distinct dimensions: ‘expressivity’ encompassing elements like blunted affect and alogia, and ‘experiential’, characterised by reduced outward displays of motivation, experience of pleasure and value for social contact.

Long-term follow-up studies are fundamental not only for understanding the longitudinal course patterns of negative symptoms but also for implementing early intervention programmes that support FEP recovery.  To date, few studies have been published in relation to the long-term trajectories of negative symptomatology after the onset of a psychotic disorder. Our results revealed three main trajectories in the dimensions mentioned above (stable, decreasing and increasing). Most of our participants were categorised within the stable and decreasing trajectories, being increasing the least represented.

Dr Rafael Romero-García joined the working group after the completion of factor and longitudinal analyses so we could leverage his experience in identifying early neuroimaging biomarkers. Although we were unable to pinpoint very early neuroimaging biomarkers, our results provided two significant insights. Firstly, individuals characterized by an increasing trajectory in expressivity dimension presented significant cortical thinning in four particular regions between 3 and 10 years after the onset of the psychotic disorder. His finding could potentially serve as a biomarker for the persistence of negative symptoms within the expressivity dimension. Lastly, our molecular analysis showed that the cortical thinning associated to expressivity was predominantly present in brain regions with lower receptor density, such as frontal regions. All together our findings suggest that the disruption of frontal regions, which play a pivotal role in the onset of negative symptoms, may be associated with the specific molecular profiles of these areas, notably the density of receptors.

This elegant neuroimaging article highlights the importance of longitudinal studies. Correlations in cross sectional data whilst important, rarely provide unequivocal insights into aetiology or indeed the effects of interventions. In contrast, the research in this paper is sophisticated, substantive, and thus significant. It points to potentially meaningful correlations between the structural integrity of regions of the brain and the clinical trajectory of the illness. It links new imaging data to clinical symptomatology and in doing so, provides further insight into the all-too-common negative symptoms of schizophrenia. Specifically, the authors found that changes following the first episode of psychosis did not become apparent immediately. Indeed, there was a considerable delay of at least several years. Furthermore, in the context of first episode psychosis, expressivity seems to be a particularly important domain of clinical symptoms in relation to cortical thinning. The article furnishes us with interesting and important findings, that perhaps move us closer to the goal of predicting outcome and timely intervention. This is why this article is of note.

Gin Malhi

Editor-in-Chief, The British Journal of Psychiatry