Resting state functional connectivity of five neural networks in bipolar disorder and schizophrenia

Abstract

Background: Bipolar disorder (BPD) and schizophrenia (SCZ) share clinical characteristics and genetic contributions. Functional dysconnectivity across various brain networks has been reported to contribute to the pathophysiology of both SCZ and BPD. However, research examining resting-state neural network dysfunction across multiple networks to understand the relationship between these two disorders is lacking.

Methods: We conducted a resting-state functional connectivity fMRI study of 35 BPD and 25 SCZ patients, and 33 controls. Using previously defined regions-of-interest, we computed the mean connectivity within and between five neural networks: default mode (DM), fronto-parietal (FP), cingulo-opercular (CO), cerebellar (CER), and salience (SAL). Repeated measures ANOVAs were used to compare groups, adjusting false discovery rate to control for multiple comparisons. The relationship of connectivity with the SANS/SAPS, vocabulary and matrix reasoning was investigated using hierarchical linear regression analyses.

Results: Decreased within-network connectivity was only found for the CO network in BPD. Across groups, connectivity was decreased between CO-CER (p<0.001), to a larger degree in SCZ than in BPD. In SCZ, there was also decreased connectivity in CO-SAL, FP-CO, and FP-CER, while BPD showed decreased CER-SAL connectivity. Disorganization symptoms were predicted by connectivity between CO-CER and CER-SAL.

Discussion: Our findings indicate dysfunction in the connections between networks involved in cognitive and emotional processing in the pathophysiology of BPD and SCZ. Both similarities and differences in connectivity were observed across disorders. Further studies are required to investigate relationships of neural networks to more diverse clinical and cognitive domains underlying psychiatric disorders.

Keywords: Bipolar; Functional connectivity; Networks; Resting state; Schizophrenia.

Fig. 1

Figure illustrating the location of regions within each of the five networks. Regions of the Frontal-Parietal network (FP) are marked in green, the Cingulo-Opercular network (CO) in yellow, the Default Mode Network (DMN) in blue the Cerebellar network (CER) in red and the Salience network (SAL) in purple.

Fig. 2

Graph illustrating within (A) and between (B) network connectivity in each of the three groups: SCZ = individuals with schizophrenia; BP = bipolar disorder; CON = healthy controls. DMN = Default Mode Network; FP = Frontal Parietal Network; CO = Cingulo-Opercular Network; CER = Cerebellar Network; SAL = Salient Network. Segments marked in red indicate networks for which connectivity measures showed significant overall group differences. Above these segments, color-coding indicates the specific groups showing differences (purple = bipolar disorder and healthy controls; yellow = schizophrenia and bipolar disorder; blue = schizophrenia and healthy controls). * p < 0.05 ** p < 0.01 *** p < 0.001gray bar, no asterisk = p < 0.1.

Fig. 3

Relationship of mean cerebellar-salience network connectivity (left) and mean cingulo-opercular-cerebellar network connectivity (right) with disorganization symptoms in individuals with bipolar disorder (red dots) and schizophrenia (blue dots). Gray shading indicates standard error.