他汀类药物对攻击性的影响：来自加州大学圣地亚哥分校他汀类药物研究的结果，一项随机对照试验。
Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial.
作者信息
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
机构信息
Department of Medicine, University of California San Diego, San Diego, CA, United States of America.
Department of Psychiatry, University of California San Diego, San Diego, CA, United States of America.
出版信息
PLoS One. 2015 Jul 1;10(7):e0124451. doi: 10.1371/journal.pone.0124451. eCollection 2015.
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.
背景
在一些研究设计中，胆固醇降低与攻击性有关。病例系列报告称，服用他汀类药物后攻击性会反复增加，但他汀类药物也有一些机制可能会降低攻击性。他汀类药物对攻击性的常见影响尚未得到明确描述。
方法
1016名成年人（692名男性，324名绝经后女性）进行了双盲、按性别分层的随机分组，分别服用安慰剂、20mg辛伐他汀或40mg普伐他汀（为期6个月）。采用改良攻击分量表的公开攻击量表（OASMa）评估行为攻击性。认为显著的性别-他汀类药物相互作用决定了按性别分层的分析。探索性分析评估了基线攻击性、睾酮变化（男性）、睡眠和年龄的影响。
结果
性别-他汀类药物相互作用显著（P=0.008）。在男性中，他汀类药物倾向于降低攻击性，普伐他汀组显著降低：差异=-1.0（标准误=0.49），P=0.038。三个明显的异常值（OASMa变化≥40分）抵消了与安慰剂相比原本很强的显著性：他汀类药物：-1.3（标准误=0.38），P=0.0007；辛伐他汀：-1.4（标准误=0.43），P=0.0011；普伐他汀：-1.2（标准误=0.45），P=0.0083。年龄≤40岁预示着他汀类药物对攻击性的降低作用更大：差异=-1.4（标准误=0.64），P=0.026。低基线攻击性者的攻击性保护作用更明显：年龄<40岁且基线攻击性低（N=40），他汀类药物与安慰剂的差异=-2.4（标准误=0.71），P=0.0016。他汀类药物（尤其是辛伐他汀）会降低睾酮水平，并增加睡眠问题。他汀类药物导致的睾酮下降预示着攻击性降低：β=0.64（标准误=0.30），P=0.034，尤其是辛伐他汀：β=1.29（标准误=0.49），P=0.009。他汀类药物导致的睡眠恶化显著预示着攻击性增加：β=2.2（标准误=0.55），P<0.001，尤其是辛伐他汀（可能解释了其中两个异常值）：β=3.3（标准误=0.83），P<0.001。在（绝经后）女性中，排除一名年轻的手术绝经女性后（N=310），他汀类药物导致的攻击性增加接近显著水平，β=0.70（标准误=0.34），P=0.039。对于更典型绝经年龄（≥45岁）的女性（N=304），不排除该女性时，攻击性增加显著：β=0.68（标准误=0.34），P=0.048 - 在修改年龄界限（≥50或≥55岁）时仍具有显著性。辛伐他汀单独使用时也观察到了显著性。他汀类药物导致的女性攻击性增加在低基线攻击性者中更强（N=175），β=0.84（标准误=0.30），P=0.006。未观察到他汀类药物对全血血清素的影响；血清素变化也未预示攻击性变化。
结论
他汀类药物对攻击性的影响因性别和年龄而异：他汀类药物通常会降低男性的攻击性；而通常会增加女性的攻击性。这两个发现都在基线攻击性较低的参与者中选择性地更为突出 - 变化方差较小，使效应更容易显现。
试验注册
Clinicaltrials.gov NCT00330980
Zotero 插件