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Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial

BACKGROUND: Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. METHODS: 1016 adults...

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Autores principales: Golomb, Beatrice A., Dimsdale, Joel E., Koslik, Hayley J., Evans, Marcella A., Lu, Xun, Rossi, Steven, Mills, Paul J., White, Halbert L., Criqui, Michael H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488854/
https://www.ncbi.nlm.nih.gov/pubmed/26132393
http://dx.doi.org/10.1371/journal.pone.0124451
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author Golomb, Beatrice A.
Dimsdale, Joel E.
Koslik, Hayley J.
Evans, Marcella A.
Lu, Xun
Rossi, Steven
Mills, Paul J.
White, Halbert L.
Criqui, Michael H.
author_facet Golomb, Beatrice A.
Dimsdale, Joel E.
Koslik, Hayley J.
Evans, Marcella A.
Lu, Xun
Rossi, Steven
Mills, Paul J.
White, Halbert L.
Criqui, Michael H.
author_sort Golomb, Beatrice A.
collection PubMed
description BACKGROUND: Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. METHODS: 1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified–Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age. RESULTS: The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): β=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (≥45): (N=304) β=0.68(SE=0.34)P=0.048 – retaining significance with modified age-cutoffs (≥50 or ≥55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) β=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change. CONCLUSION: Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression – bearing lower change-variance, rendering an effect more readily evident. TRIAL REGISTRATION: Clinicaltrials.gov NCT00330980
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spelling pubmed-44888542015-07-14 Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial Golomb, Beatrice A. Dimsdale, Joel E. Koslik, Hayley J. Evans, Marcella A. Lu, Xun Rossi, Steven Mills, Paul J. White, Halbert L. Criqui, Michael H. PLoS One Research Article BACKGROUND: Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. METHODS: 1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified–Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age. RESULTS: The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): β=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (≥45): (N=304) β=0.68(SE=0.34)P=0.048 – retaining significance with modified age-cutoffs (≥50 or ≥55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) β=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change. CONCLUSION: Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression – bearing lower change-variance, rendering an effect more readily evident. TRIAL REGISTRATION: Clinicaltrials.gov NCT00330980 Public Library of Science 2015-07-01 /pmc/articles/PMC4488854/ /pubmed/26132393 http://dx.doi.org/10.1371/journal.pone.0124451 Text en © 2015 Golomb et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Golomb, Beatrice A.
Dimsdale, Joel E.
Koslik, Hayley J.
Evans, Marcella A.
Lu, Xun
Rossi, Steven
Mills, Paul J.
White, Halbert L.
Criqui, Michael H.
Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title_full Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title_fullStr Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title_full_unstemmed Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title_short Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial
title_sort statin effects on aggression: results from the ucsd statin study, a randomized control trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488854/
https://www.ncbi.nlm.nih.gov/pubmed/26132393
http://dx.doi.org/10.1371/journal.pone.0124451
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