Suker Samir, Mihov Yoan, Wolf Andreas, Mueller Stefanie V, Hasler Gregor
Psychiatric University Hospital, University of Bern, Bern, Switzerland.
Unit of Psychiatry Research, University of Fribourg, Fribourg, Switzerland.
Schizophr Bull Open. 2023 Aug 24;4(1):sgad023. doi: 10.1093/schizbullopen/sgad023. eCollection 2023 Jan.
Dysfunction of the dopamine system is the leading neurobiological hypothesis of schizophrenia. In this study, we tested this hypothesis in the context of aberrance salience theory of delusions using catecholamine depletion. We hypothesized that acute dopamine depletion improves both positive symptoms and salience attribution in individuals with schizophrenia.
Catecholamine depletion was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 15 individuals with schizophrenia and 15 healthy volunteers. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were the Scale for the Assessment of Positive Symptoms and the Salience Attribution Test.
Catecholamine depletion transiently reduced specific psychotic symptoms in symptomatic individuals with schizophrenia, namely delusions and positive formal thought disorder (interaction treatment-by-timepoint, = .013 and = .010, respectively). We also found trends for catecholamine depletion to increase relevant bias and adaptive salience in participants with schizophrenia while decreasing them in healthy controls (interaction group-by-treatment, = .060 and = .089, respectively). Exploratory analyses revealed that in participants with schizophrenia, higher relevant bias at 3 hours after the end of AMPT treatment corresponded to lower delusional symptoms (Spearman's rho = -0.761, = .001).
This study suggests that the relationship between dopamine hyperactivity and delusional symptoms in schizophrenia is mediated by impaired attribution of salience to reward-predicting stimuli.
多巴胺系统功能障碍是精神分裂症主要的神经生物学假设。在本研究中，我们使用儿茶酚胺耗竭法，在妄想的异常显著性理论背景下检验了这一假设。我们假设急性多巴胺耗竭可改善精神分裂症患者的阳性症状和显著性归因。
通过口服α-甲基对酪氨酸（AMPT）使15名精神分裂症患者和15名健康志愿者的儿茶酚胺耗竭。研究设计包括一项随机、双盲、安慰剂对照的交叉单中心试验。主要结局指标为阳性症状评定量表和显著性归因测试。
儿茶酚胺耗竭使有症状的精神分裂症患者的特定精神病性症状暂时减轻，即妄想和阳性形式思维障碍（治疗与时间点的交互作用，分别为P = 0.013和P = 0.010）。我们还发现，儿茶酚胺耗竭有使精神分裂症患者的相关偏差和适应性显著性增加的趋势，而在健康对照者中则使其降低（组与治疗的交互作用，分别为P = 0.060和P = 0.089）。探索性分析显示，在精神分裂症患者中，AMPT治疗结束后3小时较高的相关偏差与较低的妄想症状相关（斯皮尔曼相关系数ρ = -0.761，P = 0.001）。
本研究表明，精神分裂症中多巴胺功能亢进与妄想症状之间的关系是由对奖励预测刺激的显著性归因受损介导的。
