Fondation FondaMental, Créteil, France; INSERM U955, équipe de psychiatrie translationnelle, Créteil, France, Université Paris-Est Créteil, DHU Pe-PSY, Pôle de Psychiatrie des Hôpitaux Universitaires H Mondor, Créteil, France; Bordeaux Sleep Clinique, Pellegrin University Hospital, Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000 Bordeaux, France; Clinique Jeanne d'Arc, Hôpital Privé Parisien, F-94160 Saint-Mandé, France.
Fondation FondaMental, Créteil, France; UPMC University Paris 06, UMRS 943, F-75013 Paris, France; INSERM, UMRS 943, F-75013 Paris, France.
Psychiatry Res. 2017 Aug;254:218-223. doi: 10.1016/j.psychres.2017.04.002. Epub 2017 Apr 12.
The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort. 389 participants (73% males, mean aged 32.7 years, mean illness duration 10.8 years) formed the study sample, with each comprehensively evaluated, clinically and neuropsychologically, over 2 days. 118 participants (30.3%) were defined as APA+ according to their father's age at birth (≥35 years). APA+ was associated with a wide range of cognitive dysfunctions in univariate analyses. In multivariate analyses, the only significant difference was the age at onset, with a mean 1.6 year earlier in APA+, compared to APA- (20.7 vs. 22.3 years; p=0.02). This difference is independent of sociodemographic characteristics and I.Q. No association with clinical symptomatology and treatment response was found. The present study supports the neomutation hypothesis and confirms APA as a relevant clinical variable to discriminate potential schizophrenia subtypes. Potential underlying pathophysiological mechanisms are discussed.
父亲高龄与精神分裂症风险增加相关已经得到广泛证实。本研究旨在进一步确定具有父亲高龄（APA+）的精神分裂症患者与不具有父亲高龄（APA-）的精神分裂症患者之间是否存在：（i）不同的疾病特征；（ii）对抗精神病药物的不同反应；以及（iii）不同的认知特征。参与者为稳定的社区居住者，来自非选择性的、代表性的、多中心的、被诊断为精神分裂症的人群，他们被纳入 FACE-SZ 队列。389 名参与者（73%为男性，平均年龄为 32.7 岁，平均发病病程为 10.8 年）构成了研究样本，他们在两天内接受了全面的临床和神经心理学评估。根据父亲的出生年龄（≥35 岁），118 名参与者（30.3%）被定义为 APA+。在单变量分析中，APA+与广泛的认知功能障碍相关。在多变量分析中，唯一显著的差异是发病年龄，APA+比 APA-早 1.6 年，分别为 20.7 岁和 22.3 岁（p=0.02）。这种差异独立于社会人口统计学特征和智商。未发现与临床症状和治疗反应相关的差异。本研究支持新突变假说，并证实了父亲高龄是区分潜在精神分裂症亚型的一个重要临床变量。讨论了潜在的潜在病理生理机制。
