George Tony P, Termine Angelo, Sacco Kristi A, Allen Taryn M, Reutenauer Erin, Vessicchio Jennifer C, Duncan Erica J
Program for Research in Smokers with Mental Illness (PRISM), Department of Psychiatry, Yale University School of Medicine, Substance Abuse Center, Connecticut Mental Health Center, New Haven, CT 06519, USA.
Schizophr Res. 2006 Oct;87(1-3):307-15. doi: 10.1016/j.schres.2006.05.022. Epub 2006 Jul 18.
Schizophrenics exhibit deficits in prepulse inhibition (PPI) of the startle response, and have high rates of cigarette smoking. We evaluated the effects of cigarette smoking on PPI deficits in schizophrenia, and the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related PPI enhancement.
PPI was assessed at baseline, after overnight abstinence, and after smoking reinstatement during three separate test weeks in nicotine-dependent schizophrenia (n=15) and control (n=14) smokers pre-treated with the nAChR antagonist mecamylamine (MEC; 0.0, 5.0 or 10.0 mg/day).
PPI was comparable between schizophrenia and control smokers after ad lib cigarette smoking. Overnight smoking abstinence significantly reduced PPI, while smoking reinstatement reversed abstinence-induced worsening of PPI deficits in schizophrenia. However, acute abstinence and reinstatement did not alter PPI in controls. PPI enhancement by smoking reinstatement in schizophrenia was dose-dependently blocked by MEC, whereas MEC had no effect on PPI in control smokers.
These results suggest that: 1) Non-deprived smokers with schizophrenia have comparable levels of PPI to non-deprived smoking controls; 2) In schizophrenia, PPI is impaired by smoking abstinence and improved by acute smoking reinstatement, and; 3) enhancement of PPI by cigarette smoking in schizophrenia is mediated by stimulation of central nAChRs. Our findings may contribute to understanding the increased vulnerability to nicotine dependence in schizophrenia, with implications for treatment of PPI deficits in this disorder.
精神分裂症患者在惊吓反应的前脉冲抑制（PPI）方面表现出缺陷，且吸烟率较高。我们评估了吸烟对精神分裂症患者PPI缺陷的影响，以及烟碱型乙酰胆碱受体（nAChRs）在介导吸烟相关PPI增强中的作用。
在三个独立的测试周中，对预先用nAChR拮抗剂美加明（MEC；0.0、5.0或10.0毫克/天）治疗的尼古丁依赖型精神分裂症患者（n = 15）和对照吸烟者（n = 14），在基线、过夜戒烟后以及恢复吸烟后评估PPI。
随意吸烟后，精神分裂症吸烟者和对照吸烟者的PPI相当。过夜戒烟显著降低了PPI，而恢复吸烟则逆转了戒烟引起的精神分裂症患者PPI缺陷的恶化。然而，急性戒烟和恢复吸烟对对照组的PPI没有影响。精神分裂症患者恢复吸烟引起的PPI增强被MEC剂量依赖性阻断，而MEC对对照吸烟者的PPI没有影响。
这些结果表明：1）未戒烟的精神分裂症吸烟者的PPI水平与未戒烟的吸烟对照者相当；2）在精神分裂症中，PPI因戒烟而受损，因急性恢复吸烟而改善；3）精神分裂症患者吸烟引起的PPI增强是由中枢nAChRs的刺激介导的。我们的发现可能有助于理解精神分裂症患者对尼古丁依赖的易感性增加，对该疾病中PPI缺陷的治疗具有启示意义。
