Global brain connectivity alterations in patients with schizophrenia and bipolar spectrum disorders

Global brain connectivity alterations in patients with schizophrenia and bipolar spectrum disorders


J Psychiatry Neurosci 2016;41(5):331-41

Kristina C. Skåtun, MSc; Tobias Kaufmann, PhD; Siren Tønnesen, MPsy; Guido Biele, PhD; Ingrid Melle, MD, PhD; Ingrid Agartz, MD, PhD; Dag Alnæs, PhD; Ole A. Andreassen, MD, PhD; Lars T. Westlye, PhD


Background: The human brain is organized into functionally distinct modules of which interactions constitute the human functional connectome. Accumulating evidence has implicated perturbations in the patterns of brain connectivity across a range of neurologic and neuropsychiatric disorders, but little is known about diagnostic specificity. Schizophrenia and bipolar disorders are severe mental disorders with partly overlapping symptomatology. Neuroimaging has demonstrated brain network disintegration in the pathophysiologies; however, to which degree the 2 diagnoses present with overlapping abnormalities remains unclear.

Methods: We collected resting-state fMRI data from patients with schizophrenia or bipolar disorder and from healthy controls. Aiming to characterize connectivity differences across 2 severe mental disorders, we derived global functional connectivity using eigenvector centrality mapping, which allows for regional inference of centrality or importance in the brain network.

Results: Seventy-one patients with schizophrenia, 43 with bipolar disorder and 196 healthy controls participated in our study. We found significant effects of diagnosis in 12 clusters, where pairwise comparisons showed decreased global connectivity in high-centrality clusters: sensory regions in patients with schizophrenia and subcortical regions in both patient groups. Increased connectivity occurred in frontal and parietal clusters in patients with schizophrenia, with intermediate effects in those with bipolar disorder. Patient groups differed in most cortical clusters, with the strongest effects in sensory regions.

Limitations: Methodological concerns of in-scanner motion and the use of full correlation measures may make analyses more vulnerable to noise.

Conclusion: Our results show decreased eigenvector centrality of limbic structures in both patient groups and in sensory regions in patients with schizophrenia as well as increased centrality in frontal and parietal regions in both groups, with stronger effects in patients with schizophrenia.

Submitted May 6, 2015; Revised Sept. 2, 2015; Accepted Oct. 14, 2015; Early-released Feb. 9, 2016

Acknowledgements: This work was supported by the Research Council of Norway (204966/F20, 223273, 213837); the South-Eastern Norway Regional Health Authority (2015-073, 2012-047, 2013-123); and Kristian Gerhard Jebsen Foundation. We thank the study participants and the members of NORMENT involved in data collection, the staff at the Department of Radiology and Nuclear Medicine, and Thomas D. Bjella for providing technical assistance.

Affiliations: From the Norment, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway (Skåtun, Kaufmann, Tønnesen, Melle, Agartz, Andreassen, Westlye); the Department of Child Development and Mental Health, Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway (Biele); the Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway (Agartz); and the Department of Psychology, University of Oslo, Oslo, Norway (Westlye).

Competing interests: None declared.

Contributors: K. Skåtun, I. Melle, O. Andreassen and L. Westlye designed the study. K. Skåtun, S. Tønnesen and I. Agartz acquired the data, which K. Skåtun, T. Kaufmann, G. Biele, I. Agartz, D. Alnæs and L. Westlye analyzed. K. Skåtun, T. Kaufmann, O. Andreassen and L. Westlye wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150159

Correspondence to: K.C. Skåtun, Norment, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Ullevål, Kirkeveien 166, PO Box 4956 Nydalen, 0424 Oslo, Norway;