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



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.



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.



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.
aMRC Social, Genetic & Developmental Psychiatry Centre bDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London cNIHR BRC for Mental Health, Institute of Psychiatry, Psychology and Neuroscience and SLaM NHS Trust, London, UK.
Rebecca N S
RN
Harrison
Robin M
RM
Murray
Sang Hyuck
SH
Lee
Jose
J
Paya Cano
David
D
Dempster
Charles J
CJ
Curtis
Danai
D
Dima
Fiona
F
Gaughran
Gerome
G
Breen
Simone
S
de Jong
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology*; D003024:Clozapine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; D003024:Clozapine; D018967:Risperidone