An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis

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• 作者：Vidyulata Kamath^a ; ^b ; ^{kamathv@upenn.edu} ; Paul J. Moberg^a ; ^b ; Monica E. Calkins^a ; Karin Borgmann-Winter^a ; ^d ; Catherine G. Conroy^a ; Raquel E. Gur^a ; ^c ; Christian G. Kohler^a ; Bruce I. Turetsky^a ; ^b
• 关键词：Schizophrenia prodrome ; Ultra high risk ; cAMP ; Adenosine cyclase ; DISC1
• 刊名：Schizophrenia Research
• 出版年：2012
• 期刊代码：240_09209964
• 类别：med
• 出版时间：July, 2012
• 卷：138
• 期：2-3
• 页码：280-284
• 文件大小：341 K

摘要

Background

While olfactory deficits have been reported in schizophrenia and youths at-risk for psychosis, few studies have linked these deficits to current pathophysiological models of the illness. There is evidence that disrupted cyclic adenosine 3鈥?5鈥?monophosphate (cAMP) signaling may contribute to schizophrenia pathology. As cAMP mediates olfactory signal transduction, the degree to which this disruption could manifest in olfactory impairment was ascertained. Odor-detection thresholds to two odorants that differ in the degree to which they activate intracellular cAMP were assessed in clinical risk and low-risk participants.

Method

Birhinal assessments of odor-detection threshold sensitivity to lyral and citralva were acquired in youths experiencing prodromal symptoms (n = 17) and controls at low risk for developing psychosis (n = 15). Citralva and lyral are odorants that differ in cAMP activation; citralva is a strong cAMP activator and lyral is a weak cAMP activator.

Results

The overall group-by-odor interaction was statistically significant. At-risk youths showed significantly reduced odor detection thresholds for lyral, but showed intact detection thresholds for citralva. This odor-specific threshold deficit was uncorrelated with deficits in odor identification or discrimination, which were also present. ROC curve analysis revealed that olfactory performance correctly classified at-risk and low-risk youths with greater than 97%accuracy.

Conclusions

This study extends prior findings of an odor-specific hyposmia implicating cAMP-mediated signal transduction in schizophrenia and unaffected first-degree relatives to include youths at clinical risk for developing the disorder. These results suggest that dysregulation of cAMP signaling may be present during the psychosis prodrome.