Minzenberg Michael J, Grossman Robert, New Antonia S, Mitropoulou Vivian, Yehuda Rachel, Goodman Marianne, Reynolds Diedre A, Silverman Jeremy M, Coccaro Emil F, Marcus Sue, Siever Larry J
Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY, USA.
Neuropsychopharmacology. 2006 Jan;31(1):197-203. doi: 10.1038/sj.npp.1300853.
Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.
冲动性攻击行为与中枢5-羟色胺能功能障碍有关。动物模型特别表明5-HT(1A)受体与这种行为有关。我们检验了这样一个假设，即冲动性攻击型人格障碍患者的中枢5-HT(1A)受体功能受损。共有52名患有DSM-III-R人格障碍的个体，均为身体健康的成年门诊患者，且未同时接受精神科药物治疗，在口服20毫克伊沙匹隆前后接受了系列血浆皮质醇、催乳素和体温测量。受试者完成了关于冲动性、敌意、抑郁和焦虑以及童年虐待的自我报告测量。逐步回归分析显示，在症状测量中，仅冲动性与皮质醇和催乳素峰值反应显著降低有关。边缘型人格障碍（BPD）和修订后的间歇性爆发性障碍（IED-R）诊断分别与皮质醇反应显著增加和降低有关。然而，事后分析表明，冲动性在BPD组中与皮质醇反应显著负相关，并且可能介导了BPD和IED-R与皮质醇反应改变之间的关联。体温反应与诊断或症状测量均无关。抑郁或焦虑的诊断性或维度测量，以及童年虐待的严重程度，均与皮质醇、催乳素或体温反应无显著关联。冲动性与突触后5-HT(1A)受体（或其下游）功能受损有关，这种关系可能部分解释了5-羟色胺能功能受损与BPD和IED-R等诊断之间的关联。此外，D(2)受体功能障碍可能在冲动性中起作用，而在这些疾病中5-HT(1A)细胞体自身受体功能可能未受影响。
