TY  - JOUR
A1  - Aichholzer, Mareike
A1  - Gangadin, Shiral S.
A1  - Sommer, Iris
A1  - Wijkhuis, Annemarie
A1  - De Witte, Lotje D.
A1  - Kahn, René S.
A1  - Bahn, Sabine
A1  - Drexhage, Hemmo A.
A1  - Schiweck, Carmen
T1  - Inflammatory monocyte gene signature predicts beneficial within group effect of simvastatin in patients with schizophrenia spectrum disorders in a secondary analysis of a randomized controlled trial
T2  - Brain, behavior, & immunity - health
N2  - Highlights
• Inflammatory monocyte genes were used to stratify patients in a RCT with statins.
• One group (∼30% SSD patients) showed a distinct inflammatory monocyte signature.
• Within this “inflammatory” group, statins improved PANSS scores.
• Such changes were not observed for “inflammatory” patients receiving placebo.
• Depression scores in the “inflammatory” group improved during treatment as usual.
Abstract
Immune dysregulation has been reported in schizophrenia spectrum disorders (SSD). In the past decade, several trials using anti-inflammatory agents for treatment of SSD have been completed, with so far limited success. One such anti-inflammatory agent used is simvastatin. A recent, large-scale, randomized controlled trial with simvastatin augmentation failed to show improvement in the predefined primary outcome. However, baseline inflammatory profiles were not taken into account. Here we employed a data-driven clustering approach to investigate whether patients with an inflammatory monocyte gene signature respond better to add-on simvastatin treatment than those without such a signature, over a treatment period of 2 years. In 61 patients (60 randomized, 1:1 placebo:simvastatin) and healthy controls, a previously validated monocyte gene expression signature was assessed using quantitative polymerase chain reaction. Resulting delta cycle threshold values were used to identify patient clusters. Two major patient clusters with either up- or downregulated pro-inflammatory factors were detected. Linear mixed models showed a significant three-way interaction between the inflammatory cluster, treatment, and time for psychotic symptoms. Only patients treated with simvastatin who were in the inflammatory group, showed a consistent improvement: symptom severity gradually decreased after 3 months and reached significance after 12 and 24 months compared to baseline (p.adj<0.05). The effects were small, and overall between-group effects were not significant. Here, we show that patient stratification based on inflammatory gene expression might be useful to select appropriate treatment augmentation for patients with SSD, highlighting the need for precision medicine approaches. Our findings corroborate the results of the primary analyses, showing that in the overall group, simvastatin was not effective; however, at the individual level the treatment might make a difference.
KW  - Schizophrenia
KW  - Precision medicine
KW  - Monocyte gene expression
KW  - Inflammation
KW  - Treatment response
KW  - Statin
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/78559
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-785597
SN  - 2666-3546
VL  - 26
IS  - 100551
PB  - Elsevier
CY  - Amsterdam
ER  -