Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.
<h4>Background</h4>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.&l...
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2015-01-01
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| author | Beatrice A Golomb Joel E Dimsdale Hayley J Koslik Marcella A Evans Xun Lu Steven Rossi Paul J Mills Halbert L White Michael H Criqui |
| author_facet | Beatrice A Golomb Joel E Dimsdale Hayley J Koslik Marcella A Evans Xun Lu Steven Rossi Paul J Mills Halbert L White Michael H Criqui |
| author_sort | Beatrice A Golomb |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00330980. |
| format | Article |
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| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-ea8eedeef8e04be6a410e4bf3030cc7b2025-08-20T03:53:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e012445110.1371/journal.pone.0124451Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.Beatrice A GolombJoel E DimsdaleHayley J KoslikMarcella A EvansXun LuSteven RossiPaul J MillsHalbert L WhiteMichael H Criqui<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00330980.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0124451&type=printable |
| spellingShingle | Beatrice A Golomb Joel E Dimsdale Hayley J Koslik Marcella A Evans Xun Lu Steven Rossi Paul J Mills Halbert L White Michael H Criqui Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0124451&type=printable |
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