Ventricular enlargement and progressive reduction of cortical gray matter are linked in prodromal youth who develop psychosis

Abstract

In a recent prospective longitudinal neuroimaging study, clinical high-risk (CHR) individuals who later developed full-blown psychosis showed an accelerated rate of gray matter thinning in superior and medial prefrontal cortex (PFC) and expansion of the ventricular system after applying a stringent correction for multiple comparisons. Although cortical and subcortical volume loss and enlarged ventricles are well characterized structural brain abnormalities among patients with schizophrenia, no prior study has evaluated whether these progressive changes of neuroanatomical indicators are linked in time prior to onset of psychosis. Therefore, we investigated the relationship between the changes in cortical gray matter thickness and ventricular volume using the longitudinal neuroimaging data from the North American Prodrome Longitudinal Study at the whole-brain level. The results showed that ventricular expansion is linked in time to progressive reduction of gray matter, rather than to structural changes in proximal subcortical regions, in a broadly distributed set of cortical regions among CHR youth, including superior, medial, lateral, and inferior PFC, superior temporal gyrus, and parietal cortices. In contrast, healthy controls did not show the same pattern of associations. The main findings were further replicated using a third assessment wave of MRI scans in a subset of study participants who were followed for an additional year. These findings suggest that the gray matter regions exhibiting aberrant rates of thinning in relation to psychosis risk are not limited to the PFC regions that survived the statistical threshold in our primary study, but also extend to other cortical regions previously implicated in schizophrenia.

Keywords: CHR; MRI; Prodromal; Psychosis; Schizophrenia; Ventricle.

Figure 1

Upper panel: Statistical p value maps showing regions where annualized rate of percent change (ARCH) of ventricle volume is associated with cortical gray matter thickness ARCH after controlling for age and sex in CHR sample (n = 274). False discovery rate (FDR; 0.01) correction was applied for multiple comparisons. Regions associated with expanding ventricle and cortical thinning are represented in cooler color scheme. Lower panel: partial correlation coefficients after adjusting for age and sex are mapped across the surface.

Figure 2

Scatterplot for the association between annualized rate of percent change (ARCH) of ventricular volume and mean superior frontal cortical thickness by clinical group status. Baseline and second time point (12-FU) scans were used to calculate the ARCH measures.

Figure 3

Scatterplot for the annualized rate of percent change in ventricular volume with (Left) mean cortical thickness and (right) superior frontal cortical thickness between second (12-FU) and third (24-FU) time points among CHR (n=121) and healthy control subjects (n = 64).