Table1_Risk factors, clinical correlates, and social functions of Chinese schizophrenia patients with drug-induced parkinsonism: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study.DOCX

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown.Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients.Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of co-linearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias.Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP.Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients.Clinical Trial Registration: Identifier: NCT02640911

背景：在华人群体中，由药物引起的帕金森综合征（DIP）是抗精神病药物最常见的神经精神副作用。早期预防、识别和治疗DIP对于改善精神分裂症患者的治疗效果和药物治疗依从性至关重要。然而，DIP的风险因素及其对精神分裂症临床综合征的影响尚不明确。研究目的：本研究旨在探讨华人精神分裂症患者中DIP的风险因素、临床相关性及社会功能。研究方法：自2012年至2018年，对一项多中心、观察性、真实世界、前瞻性队列研究中的华人精神分裂症人群进行了横断面分析，并进行了基线评估。参与者来自上海的四家心理健康中心，共计969名。比较了DIP组和非DIP组的社会人口学数据、药物治疗和临床变量。将与DIP诱导相关且p≤0.1的变量纳入二元逻辑模型，以分析DIP的风险因素。分别分析了第一代抗精神病药物（FGA）/第二代抗精神病药物（SGA）模型以及高、低/中D2受体抗精神病药物模型，以控制共线性偏差。将上述模型中得出的所有风险因素以及p≤0.1的临床变量纳入DIP患者的临床相关性及社会功能的多因素分析。分别分析了阳性与阴性症状量表（PANSS）模型和个人社会表现（PSP）模型，以控制共线性偏差。结果：年龄（OR = 1.03，p<0.001）、高D2受体拮抗剂抗精神病药物剂量（OR = 1.08，p = 0.032）和丙戊酸剂量（OR = 1.01，p = 0.001）是DIP的风险因素。FGA剂量不是DIP诱导的显著影响因素。精神症状，包括更严重的阴性症状（OR = 1.09，p<0.001）、较低的认知状态（OR = 1.08，p = 0.033）和较低的兴奋症状（OR = 0.91，p = 0.002），与DIP诱导显著相关。社会功能障碍，包括社会有用活动的减少（OR = 1.27，p = 0.004）、自我照顾能力的降低（OR = 1.53，p<0.001）和较轻微的干扰和攻击性行为（OR = 0.65，p<0.001），与DIP诱导显著相关。丙戊酸剂量与DIP患者的社交功能障碍（OR = 1.01，p = 0.001）和精神症状（OR = 1.01，p = 0.004）显著相关。年龄可能是一个深远的因素，它不仅影响DIP的诱导，还影响精神分裂症患者的DIP诱导的严重程度（OR = 1.02，p<0.001）以及社会功能（OR = 1.02，p<0.001）。结论：年龄、高D2受体拮抗剂抗精神病药物剂量和丙戊酸剂量是DIP的风险因素，DIP与华人精神分裂症患者的精神性症状和社会表现显著相关。合理应用或停用丙戊酸是必要的。在华人精神分裂症患者中，老年与精神症状和社会适应相关，早期干预和治疗DIP可改善精神分裂症患者的预后和社会表现。临床试验注册：标识符：NCT02640911