title: Altered striatal functional connectivity in subjects with an at-risk mental state for psychosis.
abstract: Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia;
authors.forename: Orwa
authors.initials: O
authors.lastname: Dandash
authors.forename: Alex
authors.initials: A
authors.lastname: Fornito
authors.affiliation: Department of General Psychiatry 1 and Research Division, Institute of Mental Health, Buangkok, Singapore; Office of Clinical Sciences, Graduate Medical School, Duke-National University of Singapore, Singapore, Singapore;
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC; Neuroscience and Behavioral Disorders Program, Graduate Medical School, Duke-National University of Singapore, Singapore, Singapore;
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.affiliation: Neuroscience and Behavioral Disorders Program, Graduate Medical School, Duke-National University of Singapore, Singapore, Singapore;
authors.forename: Michael W L
authors.initials: MW
authors.lastname: Chee
authors.affiliation: Department of Psychiatry and Behavioral Sciences and Center for Cognitive Neuroscience, Duke University, Durham, NC;
authors.forename: R Alison
authors.initials: RA
authors.lastname: Adcock
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia; Melbourne Health, Melbourne, Australia;
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia; School of Psychology, University of Birmingham, Edgbaston, Birmingham, UK s.j.wood@bham.ac.uk.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia;
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000503:physiopathology; D003342:Corpus Striatum / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000503:physiopathology* / Q000523:psychology; D011699:Putamen / Q000503:physiopathology; D012306:Risk; D013787:Thalamic Nuclei / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology; D055815:Young Adult
keywords: ARMS; fMRI; resting state; striatum