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Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis

Published online by Cambridge University Press:  15 April 2020

Thijs J. Burger Open the ORCID record for Thijs J. Burger [Opens in a new window] ,
Frederike Schirmbeck ,
Jentien M. Vermeulen ,
Piotr J. Quee ,
Mariken B. de Koning ,
Richard Bruggeman ,
Lieuwe de Haan  and
GROUP investigator
Thijs J. Burger*
Affiliation:
Arkin, Institute for Mental Health, Amsterdam, the Netherlands Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Frederike Schirmbeck
Affiliation:
Arkin, Institute for Mental Health, Amsterdam, the Netherlands Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Jentien M. Vermeulen
Affiliation:
Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Piotr J. Quee
Affiliation:
Department of Neurorehabilitation, Rijndam Revalidatie, Rotterdam, the Netherlands
Mariken B. de Koning
Affiliation:
Arkin, Institute for Mental Health, Amsterdam, the Netherlands Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Richard Bruggeman
Affiliation:
University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, the Netherlands Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, the Netherlands
Lieuwe de Haan
Affiliation:
Arkin, Institute for Mental Health, Amsterdam, the Netherlands Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
*
Author for correspondence: Thijs J. Burger, E-mail: thijs.burger@arkin.nl
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Abstract

Background

Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients.

Methods

In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype.

Results

Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype.

Conclusions

Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Keywords

Cognitioncognitive phenotypefamilial risklong-term outcomepsychosissiblingssymptomatic outcome
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 11 , August 2021 , pp. 1916 - 1926
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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Footnotes

Therese van Amelsvoort6, Agna A. Bartels-Velthuis4, Richard Bruggeman4,5, Wiepke Cahn7,8, Lieuwe de Haan1,2, Frederike Schirmbeck1,2, Claudia J.P. Simons6,9, Jim van Os7,10

6

Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, School for Mental Health and Neuroscience, Maastricht, the Netherlands

7

Department of Psychiatry, University Medical Center Utrecht, Brain Centre Rudolf Magnus, Utrecht University, Utrecht, the Netherlands

8

Altrecht, General Mental Health Care, Utrecht, the Netherlands

9

GGzE Institute for Mental Health Care, Eindhoven, the Netherlands

10

Department of Psychosis Studies, King's College London, King's Health Partners, Institute of Psychiatry, London, UK

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