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Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning

Published online by Cambridge University Press:  23 March 2020

A. James ,
E. Joyce ,
D. Lunn ,
M. Hough ,
L. Kenny ,
P. Ghataorhe ,
H. Fernandez ,
PM Matthews  and
M. Zarei
A. James
Affiliation:
Highfield Unit, Warneford Hospital, Oxford, UK Department of Psychiatry, Oxford University, Oxford, UK
E. Joyce
Affiliation:
Sobell Department Motor Neuroscience, UCL Institute of Neurology, London, UK
D. Lunn
Affiliation:
Department of Statistics, University of Oxford, Oxford, UK
M. Hough
Affiliation:
FMRIB Centre, John Radcliffe Hospital Oxford, University of Oxford, Oxford, UK
L. Kenny
Affiliation:
Highfield Unit, Warneford Hospital, Oxford, UK
P. Ghataorhe
Affiliation:
GSK Clinical Imaging Centre, Hammersmith Hospital, London, UK
H. Fernandez
Affiliation:
Department of Psychiatry, Oxford University, Oxford, UK Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark
PM Matthews
Affiliation:
Division of Brain Sciences, Department of Medicine, Imperial College, London, UK
M. Zarei*
Affiliation:
National Brain Mapping Centre, Shahid Beheshti University M&G campus, Tehran, Iran
*
* Corresponding author. E-mail address:[email protected](M. Zarei).
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Abstract

Background

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.

Objective

To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS.

Design

A MRI volumetric and diffusion tensor imaging study.

Participants

Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects.

Outcome measures

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.

Results

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.

Conclusions

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.

Keywords

AdolescenceSchizophreniaConnectivityStriatumFrontal cortexCognition
Type
Original article
Information
European Psychiatry , Volume 35 , May 2016 , pp. 32 - 38
Copyright
Copyright © European Psychiatry 2016

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