The promise of neuroanatomical markers in psychosis

Structural neuroimaging studies have multiplied over the last 20 years to try and advance our understanding of the pathophysiology that underlies schizophrenia and other psychoses. What these studies seem to have established is that there are indeed differences in the volume of certain brain areas between individuals affected by psychoses and those non-affected, with smaller volumes of medial temporal and frontal regions, and larger cerebral ventricles in affected individuals. Furthermore, they suggest that these differences are already evident at illness onset and possibly even in never-treated individuals in the prodromal stage, before full-blown psychotic symptoms emerge (1). This evidence has suggested that the brain alterations seen in psychosis may be long-standing, possibly resulting from an altered development of the central nervous system, and that they are not solely the result of antipsychotic treatment. While most of these studies evaluated grey matter, the more recent availability of techniques such as diffusion tensor imaging has also allowed the evaluation of the putative integrity (most often expressed as fractional anisotropy) of the white matter tracts connecting these grey matter regions. Studies that have used this approach additionally found the presence of a disrupted integrity, particularly in the white matter tracts connecting frontal and temporal areas, suggesting the presence of a ‘disconnection’ between grey matter areas that they link (2). It follows that the concomitant evaluation of both grey and white matter offers an advantageous approach, as it provides complementary information on multiple aspects of brain pathophysiology. This approach becomes even more informative when it is used to explore the correlation between brain alterations and specific clinical manifestations of the disease. Among these, negative symptoms and cognitive deficits are particularly interesting, as their presence has been associated with a less favourable response to treatment and with poorer clinical and functional outcomes. Understanding more about what neuroanatomical changes are associated with predictors of poor outcome, early in the illness, is the next step in the application of neuroimaging if this has to provide not only a basis for patient stratification in treatment trials in psychiatry, but also potentially inform the individualized treatment and management of psychiatric disorders. The article ‘Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia’ (3), published in this edition of the Journal, has followed exactly this approach. The authors have recruited a sample of individuals at their first episode of a non-affective psychosis and compared them to a group of healthy individuals. The clinical sample included in the study is noticeable in that it was composed by patients with a relatively brief duration of untreated illness (an average of 8 months), who had received only few days of treatment with antipsychotic drugs, and who had no history or current drug use. These are in fact all factors that could potentially affect brain structure. In these patients, the authors evaluated both grey and white matter structure, as well as symptom profile and cognitive function. They then explored whether or not there was a correlation between grey and white matter structure and specific symptom profiles evaluated with the Positive and negative syndrome scale (PANSS) (disorganized/ cognitive and negative), and cognitive performance in tasks in which the patients performed significantly worse than the healthy controls, namely social cognition, speed of processing and verbal memory. The study found that the presence of disorganized/cognitive symptoms was associated with both smaller volume and altered white matter integrity of the cerebellum. This is a region reported as important in the pathophysiology of schizophrenia, and in the cognitive impairments