Marcelis M, Cavalier E, Gielen J, Delespaul P, Van Os J
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research Network, EURON, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Psychol Med. 2004 Aug;34(6):1103-11. doi: 10.1017/s0033291703001715.
Previous work suggests that individuals with schizophrenia display an altered homovanillic acid (HVA) response to metabolic stress. The present study replicated and extended this paradigm, including individuals with elevated genetic risk for schizophrenia.
Patients with psychosis (n = 50), non-psychotic first-degree relatives of patients with psychosis (n = 51) and controls without psychosis (n = 50) underwent, in randomized order, double-blind administration of placebo and the glucose analogue 2-deoxy-D-glucose (2DG), which induces a mild, transient clinical state of glucoprivation. Plasma HVA and cortisol were assessed twice before the start of the 2DG/placebo infusion (baseline values), as well as four times post infusion. Data were analysed using multi-level random regression techniques.
During the stress condition, significant increases in plasma HVA and cortisol were found. The increase in plasma HVA level during the stress condition was significantly stronger in patients than in controls, whereas this was not the case in relatives v. controls. The increase in plasma cortisol during the stress condition was significantly less in patients than controls, but no significant difference in the increase of plasma cortisol during stress was found in the comparison between relatives and controls.
Patients with psychosis, but not their non-psychotic first-degree relatives, show an altered neurobiological response to metabolic stress, suggesting that this dysregulation is not a genetically transmitted vulnerability, but an illness-related effect, possibly reflecting acquired sensitization of neuroendocrine systems by repeated environmental stressors or repeated stimulation with agonistic drugs.
先前的研究表明，精神分裂症患者对代谢应激的高香草酸（HVA）反应存在改变。本研究重复并扩展了这一范式，纳入了精神分裂症遗传风险较高的个体。
精神病患者（n = 50）、精神病患者的非精神病一级亲属（n = 51）和无精神病的对照组（n = 50）按随机顺序接受安慰剂和葡萄糖类似物2-脱氧-D-葡萄糖（2DG）的双盲给药，2DG可诱导轻度、短暂的糖剥夺临床状态。在2DG/安慰剂输注开始前（基线值）对血浆HVA和皮质醇进行两次评估，并在输注后进行四次评估。使用多层次随机回归技术分析数据。
在应激状态下，血浆HVA和皮质醇显著升高。应激状态下患者血浆HVA水平的升高显著强于对照组，而亲属与对照组相比则不然。应激状态下患者血浆皮质醇的升高显著低于对照组，但亲属与对照组相比，应激状态下血浆皮质醇升高无显著差异。
精神病患者而非其非精神病一级亲属对代谢应激的神经生物学反应存在改变，这表明这种失调不是遗传传递的易感性，而是与疾病相关的效应，可能反映了神经内分泌系统因反复的环境应激源或激动剂药物的反复刺激而获得的敏感性。
