title: Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning.
abstract: Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is hypothesised, in part, to reflect functional dysconnectivity between the frontal cortex and the striatum, although structural abnormalities consistent with this hypothesis have not yet been demonstrated in adolescence.
  
  
  
  To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS.
  
  
  
  A MRI volumetric and diffusion tensor imaging study.
  
  
  
  Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects.
  
  
  
  Using probabilistic tractography, cortical regions with the highest connection probability for each striatal voxel were determined, and correlated with IQ and specific cognitive functions after co-varying for age and sex. Fractional anisotropy (FA) from individual tracts was a secondary measure.
  
  
  
  Bayesian Structural Equation modeling of FA from 12 frontostriatal tracts showed processing speed to be an intermediary variable for cognition. AOS patients demonstrated generalised cognitive impairment with specific deficits in verbal learning and memory and in processing speed after correction for IQ. Dorsolateral prefrontal cortex connectivity with the striatum correlated positively with these measures and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdalohippocampal complex, right anterior cingulate cortex, left medial orbitofrontal cortex and right dorsolateral prefrontal cortex.
  
  
  
  Frontostriatal dysconnectivity in large WM tracts that can explain core cognitive deficits are evident during adolescence. Processing speed, which is affected by alterations in WM connectivity, appears an intermediary variable in the cognitive deficits seen in schizophrenia.
authors.affiliation: Highfield Unit, Warneford Hospital, Oxford, UK; Department of Psychiatry, Oxford University, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: James
authors.affiliation: Sobell Department Motor Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Joyce
authors.affiliation: Department of Statistics, University of Oxford, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Lunn
authors.affiliation: FMRIB Centre, John Radcliffe Hospital Oxford, University of Oxford, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hough
authors.affiliation: Highfield Unit, Warneford Hospital, Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Kenny
authors.affiliation: GSK Clinical Imaging Centre, Hammersmith Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Ghataorhe
authors.affiliation: Department of Psychiatry, Oxford University, Oxford, UK; Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark.
authors.forename: H M
authors.initials: HM
authors.lastname: Fernandes
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Matthews
authors.affiliation: National Brain Mapping Centre, Shahid Beheshti University M&G campus, Tehran, Iran. Electronic address: mzarei@me.com.
authors.forename: M
authors.initials: M
authors.lastname: Zarei
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D001499:Bayes Theorem; D016022:Case-Control Studies; D003071:Cognition; D003072:Cognition Disorders / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012559:Schizophrenia / Q000503:physiopathology*; D066127:White Matter / Q000503:physiopathology*
keywords: Adolescence; Cognition; Connectivity; Frontal cortex; Schizophrenia; Striatum