González-Rodríguez Alexandre, Catalán Rosa, Penadés Rafael, Ruiz Cortés Victoria, Torra Mercè, Seeman Mary V, Bernardo Miquel
From the *Barcelona Clinic Schizophrenia Unit, Neurosciences Institute, Hospital Clinic of Barcelona, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, CIBERSAM, IDIBAPS; †Neurosciences Institute, ‡Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, Barcelona, Spain; and §Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
J Clin Psychopharmacol. 2016 Dec;36(6):580-587. doi: 10.1097/JCP.0000000000000571.
The loss of estrogens in the menopause may lead to increased vulnerability for psychotic relapse, poor clinical outcome, and a need for increased antipsychotic dose. However, confounders such as cumulative estrogen exposure and time since menopause have been inadequately studied. Our aim was to investigate potential variables capable of influencing antipsychotic response in a sample of postmenopausal women with schizophrenia.
Sixty-four postmenopausal schizophrenic women were followed in a 12-week prospective treatment-by-clinical requirement study. Duration of reproductive years was considered an indirect measure of lifetime cumulative estrogens exposure. Psychopathological assessment included the following: Positive and Negative Syndrome Scale, Personal and Social Performance, and Clinical Global Impression-Schizophrenia Scale. Response was defined as a reduction of 30% or more of Positive and Negative Syndrome Scale total scores. Antipsychotic adherence was assessed by plasma level monitoring at 4 weeks. Regression analyses were performed to investigate the association between potential confounding factors and antipsychotic response.
Forty-two participants (66%) were found to be antipsychotic responders. Time since menopause was significantly and negatively associated with overall antipsychotic response, explaining almost 42% of the variance of the model used. Smoking and cumulative estrogen exposures were associated with improvement in negative symptoms. Smoking and time since menopause were associated with improvement in excitement symptoms, and smoking was positively associated with improvement in depressive and cognitive symptoms.
Time since menopause was significantly negatively associated with antipsychotic response in postmenopausal schizophrenic women, suggesting a decline in antipsychotic response after menopause. The neurobiological basis for antipsychotic response may include a role for estrogen and nicotine receptors.
绝经后雌激素水平下降可能导致精神病复发风险增加、临床预后不良以及抗精神病药物剂量需求增加。然而，诸如累积雌激素暴露和绝经时间等混杂因素尚未得到充分研究。我们的目的是在一组绝经后精神分裂症女性样本中调查可能影响抗精神病药物反应的潜在变量。
对64名绝经后精神分裂症女性进行了一项为期12周的前瞻性按需治疗研究。生殖年限被视为终生累积雌激素暴露的间接指标。精神病理学评估包括：阳性和阴性症状量表、个人和社会功能量表以及临床总体印象-精神分裂症量表。反应被定义为阳性和阴性症状量表总分降低30%或更多。在4周时通过血浆水平监测评估抗精神病药物依从性。进行回归分析以研究潜在混杂因素与抗精神病药物反应之间的关联。
42名参与者（66%）被发现是抗精神病药物反应者。绝经时间与总体抗精神病药物反应呈显著负相关，解释了所用模型近42%的方差。吸烟和累积雌激素暴露与阴性症状改善相关。吸烟和绝经时间与兴奋症状改善相关，吸烟与抑郁和认知症状改善呈正相关。
绝经时间与绝经后精神分裂症女性的抗精神病药物反应呈显著负相关，表明绝经后抗精神病药物反应下降。抗精神病药物反应的神经生物学基础可能包括雌激素和尼古丁受体的作用。
