Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

Rebecca N.S. Harrison; Robin M. Murray; Sang Hyuck Lee; Jose Paya Cano; David Dempster; Charles J. Curtis; Danai Dima; Fiona Gaughran; Gerome Breen; Simone De Jong

doi:10.1097/YPG.0000000000000140

Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

Rebecca N.S. Harrison, Robin M. Murray, Sang Hyuck Lee, Jose Paya Cano, David Dempster, Charles J. Curtis, Danai Dima, Fiona Gaughran, Gerome Breen, Simone De Jong

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Abstract

OBJECTIVES: Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.

METHODS: A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.

RESULTS: Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.

CONCLUSION: Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Original language	English
Pages (from-to)	211-217
Journal	Psychiatric Genetics
Volume	26
Issue number	5
Early online date	7 Jul 2016
DOIs	https://doi.org/10.1097/YPG.0000000000000140
Publication status	Published - Oct 2016

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Gene-expression analysis of_HARRISON_Accepted13May2016_GOLD VoRFinal published version, 218 KBLicence: CC BY-NC-ND

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@article{7a191aa903c34aa9bf86d1241668f642,

title = "Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis",

abstract = "OBJECTIVES: Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.METHODS: A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.RESULTS: Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.CONCLUSION: Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.",

author = "Harrison, {Rebecca N.S.} and Murray, {Robin M.} and Lee, {Sang Hyuck} and {Paya Cano}, Jose and David Dempster and Curtis, {Charles J.} and Danai Dima and Fiona Gaughran and Gerome Breen and {De Jong}, Simone",

note = "This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NCND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.",

year = "2016",

month = oct,

doi = "10.1097/YPG.0000000000000140",

language = "English",

volume = "26",

pages = "211--217",

journal = "Psychiatric Genetics",

issn = "0955-8829",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

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TY - JOUR

T1 - Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

AU - Harrison, Rebecca N.S.

AU - Murray, Robin M.

AU - Lee, Sang Hyuck

AU - Paya Cano, Jose

AU - Dempster, David

AU - Curtis, Charles J.

AU - Dima, Danai

AU - Gaughran, Fiona

AU - Breen, Gerome

AU - De Jong, Simone

N1 - This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NCND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

PY - 2016/10

Y1 - 2016/10

N2 - OBJECTIVES: Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.METHODS: A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.RESULTS: Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.CONCLUSION: Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.

AB - OBJECTIVES: Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.METHODS: A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.RESULTS: Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.CONCLUSION: Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0/.

U2 - 10.1097/YPG.0000000000000140

DO - 10.1097/YPG.0000000000000140

M3 - Article

C2 - 27315048

SN - 0955-8829

VL - 26

SP - 211

EP - 217

JO - Psychiatric Genetics

JF - Psychiatric Genetics

IS - 5

ER -

Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis

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