Cullen Alexis E, Zunszain Patricia A, Dickson Hannah, Roberts Ruth E, Fisher Helen L, Pariante Carmine M, Laurens Kristin R
Department of Forensic and Neurodevelopmental Sciences (Box P023), Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom.
Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom.
Psychoneuroendocrinology. 2014 Aug;46(100):1-13. doi: 10.1016/j.psyneuen.2014.03.010. Epub 2014 Mar 29.
Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9-12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11-14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset.
下丘脑-垂体-肾上腺（HPA）轴功能异常，以日间皮质醇水平升高和/或皮质醇觉醒反应（CAR）迟钝为指标，在首发精神病患者中已被观察到，且与该人群的神经认知缺陷有关。然而，这些特征在疾病发作之前出现的程度尚不清楚。当前研究旨在确定那些因具有多种精神分裂症前驱因素（ASz）而被假定为精神病风险升高的儿童，以及有家族病史（FHx）的高危儿童，与发育正常（TD）的同龄人相比，是否具有皮质醇水平异常的特征。另一个目的是研究皮质醇水平与心理社会压力和神经认知功能的关联程度。使用一种基于社区的新型筛查程序或作为精神分裂症患者的亲属，在9至12岁的儿童中确定了33名ASz儿童、22名FHx儿童和40名TD儿童。所有参与者均未使用过抗精神病药物，且目前未因症状寻求治疗。在11至14岁时，参与者提供唾液皮质醇样本，并完成心理社会压力测量以及记忆和执行功能测试。结果表明，相对于其TD同龄人，FHx儿童的CAR迟钝（效应大小=-0.73，p=0.01），这不能用心理社会压力暴露或与这些经历相关的痛苦来解释。FHx儿童和ASz儿童的日间皮质醇水平均未升高。在FHx儿童和ASz儿童中，更明显的HPA轴功能异常（即更高的日间皮质醇水平和更明显的CAR迟钝）与言语记忆和执行功能测试中的较差表现相关。这些发现支持了这样一种观点，即精神病中描述的至少一些HPA轴异常在疾病发作之前就已出现，而不是随后的一种附带现象。我们推测，CAR迟钝可能构成精神病易感性的早期（可能由基因介导）标志物，而日间皮质醇水平升高可能仅在疾病发作临近时出现。
