Risk factors, clinical features, and polygenic risk scores in schizophrenia and schizoaffective disorder depressive-type

Charlotte A Dennison; Sophie E Legge; Leon Hubbard; Amy J Lynham; Stanley  Zammit; Peter Holmans; Alastair G Cardno; Michael J Owen; Michael C O'Donovan; James T R Walters

doi:10.1093/schbul/sbab036

Risk factors, clinical features, and polygenic risk scores in schizophrenia and schizoaffective disorder depressive-type

Charlotte A Dennison, Sophie E Legge, Leon Hubbard, Amy J Lynham, Stanley Zammit, Peter Holmans, Alastair G Cardno, Michael J Owen, Michael C O'Donovan, James T R Walters

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Abstract

There is controversy about the status of schizoaffective disorder depressive-type (SA-D), particularly whether it should be considered a form of schizophrenia or a distinct disorder. We aimed to determine whether individuals with SA-D differ from individuals with schizophrenia in terms of demographic, premorbid and lifetime clinical characteristics, and genetic liability to schizophrenia, depression and bipolar disorder. Participants were from the CardiffCOGS sample and met ICD-10 criteria for schizophrenia (n=713) or SA-D (n=151). Two samples, Cardiff Affected-sib (n=354) and Cardiff F-series (n=524), were used for replication. For all samples, phenotypic data were ascertained through structured interview, review of medical records, and an ICD-10 diagnosis made by trained researchers. Univariable and multivariable logistic regression models were used to compare individuals with schizophrenia and SA-D for demographic and clinical characteristics, and polygenic risk scores (PRS). In the CardiffCOGS, SA-D, compared to schizophrenia, was associated with female sex, childhood abuse, history of alcohol dependence, higher functioning Global Assessment Scale (GAS) score in worst episode of psychosis, lower functioning GAS score in worst episode of depression, and reduced lifetime severity of disorganised symptoms. Individuals with SA-D had higher depression PRS compared to those with schizophrenia. PRS for schizophrenia and bipolar disorder did not significantly differ between SA-D and schizophrenia. Compared to individuals with schizophrenia, individuals with SA-D had higher rates of environmental and genetic risk factors for depression and a similar genetic liability to schizophrenia. These findings are consistent with SA-D being a sub-type of schizophrenia resulting from elevated liability to both schizophrenia and depression.

Key words: Polygenic risk score; depression; psychosis; diagnosis; phenotypes

Original language	English
Article number	sbab036
Pages (from-to)	1375-1384
Number of pages	10
Journal	Schizophrenia Bulletin
Volume	47
Issue number	5
Early online date	10 Apr 2021
DOIs	https://doi.org/10.1093/schbul/sbab036
Publication status	Published - 1 Sept 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Keywords

polygenic risk score
depression
psychosis
diagnosis
phenotypes

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Dennison, C. A., Legge, S. E., Hubbard, L., Lynham, A. J., Zammit, S., Holmans, P., Cardno, A. G., Owen, M. J., O'Donovan, M. C., & Walters, J. T. R. (2021). Risk factors, clinical features, and polygenic risk scores in schizophrenia and schizoaffective disorder depressive-type. Schizophrenia Bulletin, 47(5), 1375-1384. Article sbab036. https://doi.org/10.1093/schbul/sbab036

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abstract = "There is controversy about the status of schizoaffective disorder depressive-type (SA-D), particularly whether it should be considered a form of schizophrenia or a distinct disorder. We aimed to determine whether individuals with SA-D differ from individuals with schizophrenia in terms of demographic, premorbid and lifetime clinical characteristics, and genetic liability to schizophrenia, depression and bipolar disorder. Participants were from the CardiffCOGS sample and met ICD-10 criteria for schizophrenia (n=713) or SA-D (n=151). Two samples, Cardiff Affected-sib (n=354) and Cardiff F-series (n=524), were used for replication. For all samples, phenotypic data were ascertained through structured interview, review of medical records, and an ICD-10 diagnosis made by trained researchers. Univariable and multivariable logistic regression models were used to compare individuals with schizophrenia and SA-D for demographic and clinical characteristics, and polygenic risk scores (PRS). In the CardiffCOGS, SA-D, compared to schizophrenia, was associated with female sex, childhood abuse, history of alcohol dependence, higher functioning Global Assessment Scale (GAS) score in worst episode of psychosis, lower functioning GAS score in worst episode of depression, and reduced lifetime severity of disorganised symptoms. Individuals with SA-D had higher depression PRS compared to those with schizophrenia. PRS for schizophrenia and bipolar disorder did not significantly differ between SA-D and schizophrenia. Compared to individuals with schizophrenia, individuals with SA-D had higher rates of environmental and genetic risk factors for depression and a similar genetic liability to schizophrenia. These findings are consistent with SA-D being a sub-type of schizophrenia resulting from elevated liability to both schizophrenia and depression.Key words: Polygenic risk score; depression; psychosis; diagnosis; phenotypes",

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AU - Dennison, Charlotte A

AU - Legge, Sophie E

AU - Hubbard, Leon

AU - Lynham, Amy J

AU - Zammit, Stanley

AU - Holmans, Peter

AU - Cardno, Alastair G

AU - Owen, Michael J

AU - O'Donovan, Michael C

AU - Walters, James T R

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N2 - There is controversy about the status of schizoaffective disorder depressive-type (SA-D), particularly whether it should be considered a form of schizophrenia or a distinct disorder. We aimed to determine whether individuals with SA-D differ from individuals with schizophrenia in terms of demographic, premorbid and lifetime clinical characteristics, and genetic liability to schizophrenia, depression and bipolar disorder. Participants were from the CardiffCOGS sample and met ICD-10 criteria for schizophrenia (n=713) or SA-D (n=151). Two samples, Cardiff Affected-sib (n=354) and Cardiff F-series (n=524), were used for replication. For all samples, phenotypic data were ascertained through structured interview, review of medical records, and an ICD-10 diagnosis made by trained researchers. Univariable and multivariable logistic regression models were used to compare individuals with schizophrenia and SA-D for demographic and clinical characteristics, and polygenic risk scores (PRS). In the CardiffCOGS, SA-D, compared to schizophrenia, was associated with female sex, childhood abuse, history of alcohol dependence, higher functioning Global Assessment Scale (GAS) score in worst episode of psychosis, lower functioning GAS score in worst episode of depression, and reduced lifetime severity of disorganised symptoms. Individuals with SA-D had higher depression PRS compared to those with schizophrenia. PRS for schizophrenia and bipolar disorder did not significantly differ between SA-D and schizophrenia. Compared to individuals with schizophrenia, individuals with SA-D had higher rates of environmental and genetic risk factors for depression and a similar genetic liability to schizophrenia. These findings are consistent with SA-D being a sub-type of schizophrenia resulting from elevated liability to both schizophrenia and depression.Key words: Polygenic risk score; depression; psychosis; diagnosis; phenotypes

AB - There is controversy about the status of schizoaffective disorder depressive-type (SA-D), particularly whether it should be considered a form of schizophrenia or a distinct disorder. We aimed to determine whether individuals with SA-D differ from individuals with schizophrenia in terms of demographic, premorbid and lifetime clinical characteristics, and genetic liability to schizophrenia, depression and bipolar disorder. Participants were from the CardiffCOGS sample and met ICD-10 criteria for schizophrenia (n=713) or SA-D (n=151). Two samples, Cardiff Affected-sib (n=354) and Cardiff F-series (n=524), were used for replication. For all samples, phenotypic data were ascertained through structured interview, review of medical records, and an ICD-10 diagnosis made by trained researchers. Univariable and multivariable logistic regression models were used to compare individuals with schizophrenia and SA-D for demographic and clinical characteristics, and polygenic risk scores (PRS). In the CardiffCOGS, SA-D, compared to schizophrenia, was associated with female sex, childhood abuse, history of alcohol dependence, higher functioning Global Assessment Scale (GAS) score in worst episode of psychosis, lower functioning GAS score in worst episode of depression, and reduced lifetime severity of disorganised symptoms. Individuals with SA-D had higher depression PRS compared to those with schizophrenia. PRS for schizophrenia and bipolar disorder did not significantly differ between SA-D and schizophrenia. Compared to individuals with schizophrenia, individuals with SA-D had higher rates of environmental and genetic risk factors for depression and a similar genetic liability to schizophrenia. These findings are consistent with SA-D being a sub-type of schizophrenia resulting from elevated liability to both schizophrenia and depression.Key words: Polygenic risk score; depression; psychosis; diagnosis; phenotypes

KW - polygenic risk score

KW - depression

KW - psychosis

KW - diagnosis

KW - phenotypes

U2 - 10.1093/schbul/sbab036

DO - 10.1093/schbul/sbab036

M3 - Article (Academic Journal)

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SN - 0586-7614

VL - 47

SP - 1375

EP - 1384

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

IS - 5

M1 - sbab036

ER -

Risk factors, clinical features, and polygenic risk scores in schizophrenia and schizoaffective disorder depressive-type

Abstract

Bibliographical note

Keywords

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