Turetsky Bruce I, Moberg Paul J
Department of Psychiatry, University of Pennsylvania, 10th Floor, Gates Building, 3400 Spruce St., Philadelphia, PA 19104, USA.
Am J Psychiatry. 2009 Feb;166(2):226-33. doi: 10.1176/appi.ajp.2008.07071210. Epub 2008 Dec 15.
Although olfactory deficits are common in schizophrenia, their underlying pathophysiology remains unknown. Recent evidence has suggested that cAMP signaling may be disrupted in schizophrenia. Since cAMP mediates signal transduction in olfactory receptor neurons, this could contribute to the etiology of observed olfactory deficits. This study was designed to test this hypothesis by determining odor detection threshold sensitivities to two odorants that differ in their relative activations of this intracellular cAMP signaling cascade.
Thirty schizophrenia patients, 25 healthy comparison subjects, and 19 unaffected first-degree relatives of schizophrenia patients were studied. Odor detection threshold sensitivities were measured for the two odorants citralva and lyral. Although both have fruity/floral scents, citralva strongly activates adenylyl cyclase to increase cAMP levels, while lyral is a very weak activator of adenylyl cyclase.
There was a significant group-by-odor interaction. Both schizophrenia patients and unaffected first-degree relatives were impaired in their ability to detect lyral versus citralva. Comparison subjects were equally sensitive to both odorants. This selective deficit could not be explained by differences in age, sex, smoking, clinical symptom profile, or medication use.
This study establishes the presence of an odor-specific hyposmia that may denote a disruption of cAMP-mediated signal transduction in schizophrenia. The presence of a parallel deficit in the patients' unaffected first-degree relatives suggests that this deficit is genetically mediated. Although additional physiological studies are needed to confirm the underlying mechanism, these results offer strong inferential support for the hypothesis that cAMP signaling is dysregulated in schizophrenia.
虽然嗅觉缺陷在精神分裂症中很常见，但其潜在的病理生理学仍不清楚。最近的证据表明，环磷酸腺苷（cAMP）信号传导在精神分裂症中可能受到破坏。由于cAMP介导嗅觉受体神经元中的信号转导，这可能导致观察到的嗅觉缺陷的病因。本研究旨在通过确定对两种在细胞内cAMP信号级联的相对激活程度上有所不同的气味剂的气味检测阈值敏感性来检验这一假设。
对30名精神分裂症患者、25名健康对照者以及19名未受影响的精神分裂症患者的一级亲属进行了研究。测量了对柠檬醛和铃兰醛这两种气味剂的气味检测阈值敏感性。虽然两者都有水果/花香气味，但柠檬醛强烈激活腺苷酸环化酶以增加cAMP水平，而铃兰醛是腺苷酸环化酶的非常弱的激活剂。
存在显著的组×气味相互作用。精神分裂症患者和未受影响的一级亲属在检测铃兰醛与柠檬醛的能力上均受损。对照者对两种气味剂同样敏感。这种选择性缺陷无法用年龄、性别、吸烟、临床症状特征或药物使用的差异来解释。
本研究证实了存在一种气味特异性嗅觉减退，这可能表明精神分裂症中cAMP介导的信号转导受到破坏。患者未受影响的一级亲属中存在类似的缺陷表明这种缺陷是由基因介导的。虽然需要更多的生理学研究来证实潜在机制，但这些结果为cAMP信号传导在精神分裂症中失调的假设提供了有力的推断支持。
