Cortical Volume Differences in Subjects at Risk for Psychosis Are Driven by Surface Area

Abstract

In subjects at risk for psychosis, the studies on gray matter volume (GMV) predominantly reported volume loss compared with healthy controls (CON). However, other important morphological measurements such as cortical surface area (CSA) and cortical thickness (CT) were not systematically compared. So far, samples mostly comprised subjects at genetic risk or at clinical risk fulfilling an ultra-high risk (UHR) criterion. No studies comparing UHR subjects with at-risk subjects showing only basic symptoms (BS) investigated the differences in CSA or CT. Therefore, we aimed to unravel the contribution of the 2 morphometrical measures constituting the cortical volume (CV) and to test whether these groups inhere different morphometric features. We conducted a surface-based morphometric analysis in 34 CON, 46 BS, and 39 UHR to examine between-group differences in CV, CSA, and CT vertex-wise across the whole cortex. Compared with BS and CON, UHR individuals presented increased CV in frontal and parietal regions, which was driven by larger CSA. These groups did not differ in CT. Yet, at-risk subjects who later developed schizophrenia showed thinning in the occipital cortex. Furthermore, BS presented increased CSA compared with CON. Our results suggest that volumetric differences in UHR subjects are driven by CSA while CV loss in converters seems to be based on cortical thinning. We attribute the larger CSA in UHR to aberrant pruning representing a vulnerability to develop psychotic symptoms reflected in different levels of vulnerability for BS and UHR, and cortical thinning to a presumably stress-related cortical decomposition.

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study

“…On the other hand, there is growing evidence that variations of prefrontal CT are related to different at-risk phenotypes and the onset of early and late neurodevelopmental disturbances [ 25 , 82 ]. Different anatomical trajectories have been reported in schizotypy [ 35 ], between different at-risk states [ 83 ] and particularly in CHR individuals who subsequently develop psychosis [ 82 , 84 ]. Transition to psychosis has been associated with a steeper cortical thinning of heteromodal cortices, including the mOFC/vmPFC, compared to CHR individuals who do not convert to psychosis and healthy controls [ 85 – 88 ].…”

Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 2,952 Individuals Assessed in a Worldwide ENIGMA Study

“…On the other hand, there is growing evidence that variations of prefrontal CT are related to different atrisk phenotypes and the onset of early and late neurodevelopmental disturbances [25,82]. Different anatomical trajectories have been reported in schizotypy [35], between different at-risk states [83] and particularly in CHR individuals who subsequently develop psychosis [82,84]. Transition to psychosis has been associated with a steeper cortical thinning of heteromodal cortices, including the mOFC/vmPFC, compared to CHR individuals who do not convert to psychosis and healthy controls [85][86][87][88].…”

Cortical Thickness Abnormalities at Different Stages of the Illness Course in Schizophrenia

“… Individuals with CHR have demonstrated varying CTh alterations, with those who subsequently developed psychosis having greater abnormalities. Cortical thinning has been reported in patients with FEP in prefrontal, lateral temporal, and parietal cortex, albeit with negative findings. Discrepancies might be related to small sample sizes, variable sample characteristics, medication status, and analytical methods.…”