Functional brain networks in the schizophrenia spectrum and bipolar disorder with psychosis

Abstract

Psychotic experiences have been proposed to lie on a spectrum, ranging from subclinical experiences to treatment-resistant schizophrenia. We aimed to characterize functional connectivity and brain network characteristics in relation to the schizophrenia spectrum and bipolar disorder with psychosis to disentangle neural correlates to psychosis. Additionally, we studied antipsychotic medication and lithium effects on network characteristics. We analyzed functional connectivity strength and network topology in 487 resting-state functional MRI scans of individuals with schizophrenia spectrum disorder (SCZ), bipolar disorder with a history of psychotic experiences (BD), treatment-naïve subclinical psychosis (SCP), and healthy controls (HC). Since differences in connectivity strength may confound group comparisons of brain network topology, we analyzed characteristics of the minimum spanning tree (MST), a relatively unbiased backbone of the network. SCZ and SCP subjects had a lower connectivity strength than BD and HC individuals but showed no differences in network topology. In contrast, BD patients showed a less integrated network topology but no disturbances in connectivity strength. No differences in outcome measures were found between SCP and SCZ, or between BD patients that used antipsychotic medication or lithium and those that did not. We conclude that functional networks in patients prone to psychosis have different signatures for chronic SCZ patients and SCP compared to euthymic BD patients, with a limited role for medication. Connectivity strength effects may have confounded previous studies, as no functional network alterations were found in SCZ after strict correction for connectivity strength.

Fig. 1. MST visualizations.

a–c Brain regions and their connections are visualized as nodes (circles) and edges (lines). Red nodes are leaf nodes with only one connection. a Path-like MST with a diameter of twelve edges. b Intermediate between a path-like and a star-like MST with a diameter of six edges. The green node has a higher degree (five connecting edges) than the red leaf nodes. c Star-like MST: The green node is a node with high betweenness centrality: When connecting any two nodes in the network you have to pass the green node. Kappa, a measure that characterizes the degree distribution, is highest for a, intermediate for b, and lowest for c.

Fig. 2. Visualization of regional degree differences between the networks of psychosis groups and age-matched healthy controls.

The nodal size corresponds to their degree. Blue nodes mark regions that do not differ compared to healthy controls, while red nodes mark regions with a lower degree and green nodes mark regions with a higher degree compared to controls. HC healthy controls, SCP subclinical psychosis, SCZ schizophrenia spectrum disorder, BD bipolar disorder with psychosis.

Fig. 3. Different neural mechanisms to psychosis in the schizophrenia spectrum and bipolar disorder.

a In the schizophrenia spectrum, the resting-state MRI network is characterized by decreased connectivity strength, while the topology of the network does not differ from controls. b In patients with bipolar disorder with a history of psychosis, the connectivity strength does not differ from controls, but the network topology is less integrated.