University of Worcester Worcester Research and Publications
 
  USER PANEL:
  ABOUT THE COLLECTION:
  CONTACT DETAILS:

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder

Allardyce, J., Leonenko, G., Hamshere, M.L., Pardiñas, A., Forty, L., Knott, Sarah, Gordon-Smith, Katherine ORCID: https://orcid.org/0000-0003-4083-1143, Porteus, D., Haywood, C., Di Florio, A., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, McIntosh, A., Owen, M., Holmans, P., Walters, J., Craddock, N., Jones, I., O'Donovan, M.C. and Escott-Price, V. (2018) Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder. JAMA Psychiatry, 75 (1). pp. 28-35. ISSN Print: 2168-622X Online: 2168-6238

[img] Text
Allardyce_A stratification study of bipolar disorder_accepted version post refereeing.docx - Accepted Version
Restricted to Repository staff only

Download (310kB) | Request a copy
[img]
Preview
Text
Allardyce_A stratification study of bipolar disorder_accepted version post refereeing (1).pdf - Accepted Version

Download (420kB) | Preview
[img]
Preview
Text
jamapsychiatry_Allardyce_2017_oi_170083.pdf - Published Version
Available under License Creative Commons Attribution.

Download (443kB) | Preview

Abstract

Importance
Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes/mechanisms.
Objectives
To investigate the relationship between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRS) and psychotic presentations of BD, using clinical descriptions which consider both occurrence and level of mood-incongruent psychotic features.
Design
Case-control design: using multinomial logistic regression, to estimate differential associations of PRS across categories of cases and controls.
Settings & Participants
4399 BD cases, 2966 (67%) female, mean age-at-interview 46 [sd 12] years, from the BD Research Network (BDRN) were included in the final analyses. For comparison genotypic data for 4976 schizophrenia cases and 9012 controls from the Type-1 diabetes genetics consortium and Generation Scotland were included.
Exposure
Standardised PRS, calculated using alleles with an association p-value threshold < 0.05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, adjusted for the first 10 population principal components and genotyping-platform.
Main outcome measure
Multinomial logit models estimated PRS associations with BD stratified by (1) Research Diagnostic Criteria (RDC) BD subtypes (2) Lifetime occurrence of psychosis.(3) Lifetime mood-incongruent psychotic features and (4) ordinal logistic regression examined PRS associations across levels of mood-incongruence. Ratings were derived from the Schedule for Clinical Assessment in Neuropsychiatry interview (SCAN) and the Bipolar Affective Disorder Dimension Scale (BADDS).
Results
Across clinical phenotypes, there was an exposure-response gradient with the strongest PRS association for schizophrenia (RR=1.94, (95% C.I. 1.86, 2.01)), then schizoaffective BD (RR=1.37, (95% C.I. 1.22, 1.54)), BD I (RR= 1.30, (95% C.I. 1.24, 1.36)) and BD II (RR=1.04, (95% C.I. 0.97, 1.11)). Within BD cases, there was an effect gradient, indexed by the nature of psychosis, with prominent mood-incongruent psychotic features having the strongest association (RR=1.46, (95% C.I. 1.36, 1.57)), followed by mood-congruent psychosis (RR= 1.24, (95% C.I. 1.17, 1.33)) and lastly, BD cases with no history of psychosis (RR=1.09, (95% C.I. 1.04, 1.15)).
Conclusion
We show for the first time a polygenic-risk gradient, across schizophrenia and bipolar disorder, indexed by the occurrence and level of mood-incongruent psychotic symptoms.

Item Type: Article
Additional Information:

The online-first version of the full-text can be accessed via the Official URL.

Please note that a title of post-print has changed post acceptance date.

Uncontrolled Discrete Keywords: biploar, schizophrenia, psychotic symptoms, mood, mental health
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
Related URLs:
Copyright Info: Open Access
Depositing User: Katherine Gordon-Smith
Date Deposited: 30 Nov 2017 09:55
Last Modified: 09 Jul 2020 11:45
URI: https://eprints.worc.ac.uk/id/eprint/6019

Actions (login required)

View Item View Item
 
     
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.