title: Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study.
abstract: Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
  
  
  
  We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
  
  
  
  ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
  
  
  
  Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: F
authors.initials: F
authors.lastname: Ji
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: Z
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: J S
authors.initials: JS
authors.lastname: Poh
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Krishnan
authors.affiliation: Research Division,Institute of Mental Health,Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Research Division,Institute of Mental Health,Singapore.
authors.forename: G
authors.initials: G
authors.lastname: Rekhi
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Duke University,Durham, NC,USA.
authors.forename: R S E
authors.initials: RS
authors.lastname: Keefe
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Duke University,Durham, NC,USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Adcock
authors.affiliation: School of Psychology,University of Birmingham,Edgbaston,UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Wood
authors.affiliation: Monash Clinical and Imaging Neuroscience,School of Psychology and Psychiatry & Monash Biomedical Imaging,Monash University,Australia.
authors.forename: A
authors.initials: A
authors.lastname: Fornito
authors.affiliation: Departments of Psychiatry and Radiology,Brigham and Women's Hospital,Harvard Medical School,Boston, MA,USA.
authors.forename: O
authors.initials: O
authors.lastname: Pasternak
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: M W L
authors.initials: MW
authors.lastname: Chee
authors.affiliation: Center for Cognitive Neuroscience,Neuroscience and Behavioral Disorder Program,Duke-NUS Medical School,National University of Singapore,Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D012306:Risk; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
keywords: At risk for psychosis; LYRIKS; functional connectivity; salience network; transition to psychosis; white-matter microstructure