Swerdlow Neal R, Stephany Nora, Wasserman Lindsay C, Talledo Jo, Sharp Richard, Minassian Arpi, Auerbach Pamela P
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA.
Schizophr Res. 2005 Jan 1;72(2-3):169-83. doi: 10.1016/j.schres.2004.03.022.
People are normally slower to learn a CS-UCS association if they first experience the CS without the UCS. This normal slowing, termed "latent inhibition" (LI), is reported by some to be absent in schizophrenia patients. Our previous studies detected generalized learning deficits but not LI deficits in schizophrenia patients, using between-subject auditory and visual LI paradigms. To understand our divergent results, we developed a within-subject visual LI paradigm that detects LI in normal male subjects that we previously reported to be disrupted by acute treatment with dopamine agonists. In the present study, we verified the ability of this dopamine-sensitive within-subject LI paradigm to detect LI among both male and female normal control subjects, and then used this paradigm to assess LI in schizophrenia patients. Among normals, LI exhibited no sex differences or menstrual cyclicity. Compared to normals, schizophrenia patients exhibited learning deficits with both preexposed (PE) and non-preexposed (NPE) stimuli. Despite these generalized deficits, both acutely hospitalized patients and stable outpatients with schizophrenia exhibited robust LI, as evidenced by significantly faster learning with NPE than PE stimuli. LI deficits in schizophrenia may be paradigm-specific and are not detected by a paradigm that we previously reported to be sensitive to disruption by dopamine agonists.
如果人们首先经历了条件刺激（CS）而没有无条件刺激（UCS），那么他们通常会更慢地学习CS-UCS关联。这种正常的学习速度减慢被称为“潜伏抑制”（LI），据一些人报道，精神分裂症患者不存在这种现象。我们之前的研究使用受试者间听觉和视觉LI范式，在精神分裂症患者中检测到了一般性学习缺陷，但未检测到LI缺陷。为了理解我们不同的研究结果，我们开发了一种受试者内视觉LI范式，该范式在我们之前报道的因多巴胺激动剂急性治疗而受到干扰的正常男性受试者中检测到了LI。在本研究中，我们验证了这种对多巴胺敏感的受试者内LI范式在男性和女性正常对照受试者中检测LI的能力，然后使用该范式评估精神分裂症患者的LI。在正常人中，LI没有表现出性别差异或月经周期变化。与正常人相比，精神分裂症患者在预暴露（PE）和非预暴露（NPE）刺激下均表现出学习缺陷。尽管存在这些一般性缺陷，但急性住院患者和稳定的精神分裂症门诊患者均表现出较强的LI，NPE刺激下的学习速度明显快于PE刺激就是证明。精神分裂症患者的LI缺陷可能是特定于范式的，并且我们之前报道的对多巴胺激动剂干扰敏感的范式无法检测到这种缺陷。
