Differential changes on the white matter network of the brain in ultra-high risk for psychosis and first-episode psychosis

Abstract

A comprehensive figure of dysconnectivity in schizophrenia could be explored at the network level that not only accounts for local but also global organizational characteristics. However, no study has concurrently explored alteration in the white matter (WM) network of the brain of first-episode psychosis (FEP) and its prodromal stage to see whether differential changes in the structural network would exist according to the different stages of psychosis.

Thirty-seven subjects with ultra-high risk for psychosis (UHR), 21 patients with FEP, and 37 healthy controls (HC) were recruited in the study. 3-Tesla T1 structural and diffusion tensor images were reconstructed as weighted WM networks of the brain by measuring number of axonal streamlines between 82 cortical and subcortical regions. Then, graph measures extracted from the networks were compared.

Although global graph measures reflecting efficiency or small-world property of a network were not different between groups, the UHR group showed a higher assortativity coefficient compared to the FEP group and a higher modularity Q, without alteration in global clustering coefficient, compared to the HC group. At the local level, the FEP group showed a weaker WM connection between the left hippocampus and ipsilateral parahippocampal gyrus and a stronger WM connection between the left thalamus and ipsilateral superior frontal gyrus compared to the UHR and HC groups. More rightward asymmetry of the connections between both hippocampi and ipsilateral parahippocampal gyri was seen in the FEP compared to the UHR and HC groups, and rightward asymmetry of the connections correlated positively with psychotic symptoms and negatively with level of functioning in the UHR group. The participation coefficient of the right pallidum increased in the FEP compared to the UHR and HC groups, and the measure positively correlated with nonspecific psychiatric symptoms in the FEP group.

UHR has enhanced resilience and adaptability of the WM network that may reflect highly variable prognosis of the stage among psychosis-continuum and defensive mechanism of the network against further damage. On the other hand, FEP has alteration mainly in the cortico-subcortical connectivity. These differential changes may reflect underlying biological mechanisms of developmental process leading to psychosis.