Turetsky Bruce I, Kohler Christian G, Gur Raquel E, Moberg Paul J
Neuropsychiatry Division, Department of Psychiatry, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Schizophr Res. 2008 Jul;102(1-3):220-9. doi: 10.1016/j.schres.2008.03.013. Epub 2008 May 5.
Efforts to characterize genetic vulnerability to schizophrenia are increasingly focused on the identification of endophenotypes--neurobiological abnormalities that are evident in individuals at risk. Behavioral studies have demonstrated olfactory impairments in odor detection and identification in unaffected 1st-degree relatives of schizophrenia patients, suggesting that abnormalities in this simple sensory system may serve as candidate endophenotypes. It is unclear, however, whether these behavioral abnormalities reflect basic olfactory sensory processing deficits or nonspecific disruptions of attention and cognition.
Unirhinal chemosensory olfactory evoked potentials were acquired from 14 unaffected 1st-degree relatives of schizophrenia patients and 20 healthy individuals with equivalent age and gender distributions, using 3 different concentrations of hydrogen sulfide. Subjects were also assessed behaviorally for ability to detect and identify odors.
Family members exhibited left nostril olfactory detection impairments and bilateral olfactory identification abnormalities. They had reduced evoked potential response amplitudes for the initial N1 component in the left nostril. The subsequent P2 evoked potential response was reduced bilaterally. The pattern and magnitude of family member deficits were comparable to those previously observed for schizophrenia patients.
1st-degree relatives of schizophrenia patients exhibit specific neurophysiological impairments in early olfactory sensory processing. The presence of these neurophysiological abnormalities in both schizophrenia patients and their unaffected 1st-degree relatives suggests that these represent genetically mediated vulnerability markers or endophenotypes of the illness.
确定精神分裂症遗传易感性的研究越来越集中于内表型的识别——即在有患病风险个体中明显存在的神经生物学异常。行为学研究表明，精神分裂症患者未患病的一级亲属在气味检测和识别方面存在嗅觉障碍，这表明这个简单感觉系统的异常可能是候选内表型。然而，尚不清楚这些行为异常是反映了基本嗅觉感觉处理缺陷，还是注意力和认知的非特异性干扰。
使用3种不同浓度的硫化氢，从14名精神分裂症患者未患病的一级亲属和20名年龄和性别分布相当的健康个体中获取单侧化学感觉嗅觉诱发电位。还对受试者进行了气味检测和识别能力的行为评估。
家庭成员表现出左鼻孔嗅觉检测障碍和双侧嗅觉识别异常。他们左鼻孔初始N1成分的诱发电位反应幅度降低。随后的双侧P2诱发电位反应降低。家庭成员缺陷的模式和程度与先前在精神分裂症患者中观察到的相当。
精神分裂症患者的一级亲属在早期嗅觉感觉处理方面表现出特定的神经生理损伤。精神分裂症患者及其未患病的一级亲属中均存在这些神经生理异常，这表明这些代表了该疾病的遗传介导易感性标志物或内表型。
