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An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers
RATIONALE: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant transl...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069418/ https://www.ncbi.nlm.nih.gov/pubmed/35511258 http://dx.doi.org/10.1007/s00213-022-06156-y |
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author | De Giorgi, Riccardo Quinton, Alice M. G. Waters, Shona Cowen, Philip J. Harmer, Catherine J. |
author_facet | De Giorgi, Riccardo Quinton, Alice M. G. Waters, Shona Cowen, Philip J. Harmer, Catherine J. |
author_sort | De Giorgi, Riccardo |
collection | PubMed |
description | RATIONALE: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition. OBJECTIVES: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. METHODS: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. RESULTS: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F(1,51) = 4.99, p = 0.03), but also an increase in anxiety scores (F(1,51) = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F(1,25) = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. CONCLUSIONS: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04652089. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-022-06156-y. |
format | Online Article Text |
id | pubmed-9069418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-90694182022-05-04 An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers De Giorgi, Riccardo Quinton, Alice M. G. Waters, Shona Cowen, Philip J. Harmer, Catherine J. Psychopharmacology (Berl) Original Investigation RATIONALE: Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition. OBJECTIVES: We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. METHODS: Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. RESULTS: Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F(1,51) = 4.99, p = 0.03), but also an increase in anxiety scores (F(1,51) = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F(1,25) = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. CONCLUSIONS: We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04652089. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-022-06156-y. Springer Berlin Heidelberg 2022-05-05 2022 /pmc/articles/PMC9069418/ /pubmed/35511258 http://dx.doi.org/10.1007/s00213-022-06156-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Investigation De Giorgi, Riccardo Quinton, Alice M. G. Waters, Shona Cowen, Philip J. Harmer, Catherine J. An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title | An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title_full | An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title_fullStr | An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title_full_unstemmed | An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title_short | An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
title_sort | experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069418/ https://www.ncbi.nlm.nih.gov/pubmed/35511258 http://dx.doi.org/10.1007/s00213-022-06156-y |
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