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Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains

Published online by Cambridge University Press:  02 November 2017

R. Blakey ,
S. Ranlund ,
E. Zartaloudi ,
W. Cahn ,
S. Calafato ,
M. Colizzi ,
B. Crespo-Facorro ,
C. Daniel ,
Á. Díez-Revuelta  and
M. Di Forti
...Show all authors
R. Blakey
Affiliation:
Division of Psychiatry, University College London, London, UK
S. Ranlund*
Affiliation:
Division of Psychiatry, University College London, London, UK Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
E. Zartaloudi
Affiliation:
Division of Psychiatry, University College London, London, UK
W. Cahn
Affiliation:
Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
S. Calafato
Affiliation:
Division of Psychiatry, University College London, London, UK
M. Colizzi
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
B. Crespo-Facorro
Affiliation:
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria–IDIVAL, Santander, Spain
C. Daniel
Affiliation:
Division of Psychiatry, University College London, London, UK
Á. Díez-Revuelta
Affiliation:
Division of Psychiatry, University College London, London, UK Laboratory of Cognitive and Computational Neuroscience – Centre for Biomedical Technology (CTB), Complutense University and Technical University of Madrid, Madrid, Spain
M. Di Forti
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
C. Iyegbe
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
A. Jablensky
Affiliation:
Centre for Clinical Research in Neuropsychiatry, The University of Western Australia, Perth, Western Australia, Australia
R. Jones
Affiliation:
Division of Psychiatry, University College London, London, UK
M.-H. Hall
Affiliation:
Psychology Research Laboratory, Harvard Medical School, McLean Hospital, Belmont, MA, USA
R. Kahn
Affiliation:
Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
L. Kalaydjieva
Affiliation:
Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia
E. Kravariti
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
K. Lin
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK Nuffield Department of Population Health, University of Oxford, Oxford, UK
C. McDonald
Affiliation:
Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Ireland
A. M. McIntosh
Affiliation:
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK
M. Picchioni
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
J. Powell
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
A. Presman
Affiliation:
Division of Psychiatry, University College London, London, UK
D. Rujescu
Affiliation:
Department of Psychiatry, Ludwig-Maximilians University of Munich, Munich, Germany Department of Psychiatry, Psychotherapy and Psychosomatics, University of Halle Wittenberg, Halle, Germany
K. Schulze
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
M. Shaikh
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK North East London Foundation Trust, London, UK
J. H. Thygesen
Affiliation:
Division of Psychiatry, University College London, London, UK
T. Toulopoulou
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK Department of Psychology, Bilkent University, Main Campus, Bilkent, Ankara, Turkey Department of Psychology, the University of Hong Kong, Pokfulam Rd, Hong Kong SAR, China The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, The Hong Kong Jockey Club Building for Interdisciplinary Research, Hong Kong SAR, China
N. Van Haren
Affiliation:
Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
J. Van Os
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK Department of Psychiatry and Psychology, Maastricht University Medical Centre, EURON, Maastricht, The Netherlands
M. Walshe
Affiliation:
Division of Psychiatry, University College London, London, UK Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
R. M. Murray
Affiliation:
Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK
E. Bramon*
Affiliation:
Division of Psychiatry, University College London, London, UK Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust, London, UK Institute of Cognitive Neuroscience, University College London, London, UK
*
Author for correspondence: Dr S. Ranlund, Ph.D., E-mail: siri.ranlund@kcl.ac.uk and e.bramon@ucl.ac.uk
Author for correspondence: Dr S. Ranlund, Ph.D., E-mail: siri.ranlund@kcl.ac.uk and e.bramon@ucl.ac.uk
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Abstract

Background

A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.

Methods

This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.

Results

The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.

Conclusions

The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.

Keywords

Lateral ventricular volumeP300schizophreniaverbal memoryunaffected relativesworking memory

Information

Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 8 , June 2018 , pp. 1325 - 1340
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

†

Contributed equally as joint first authors.

‡

Co-authors who are members of the Psychosis Endophenotypes International Consortium (PEIC) and the Genetic Risk and Outcome of Psychosis (GROUP) consortium are listed at the end of this paper.

§

Members of the Wellcome Trust Case Control Consortium 2 (WTCCC2) are listed in the Supplement.

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