TY - JOUR
T1 - An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis
AU - Kamath, Vidyulata
AU - Moberg, Paul J.
AU - Calkins, Monica E.
AU - Borgmann-Winter, Karin
AU - Conroy, Catherine G.
AU - Gur, Raquel E.
AU - Kohler, Christian G.
AU - Turetsky, Bruce I.
N1 - Funding Information:
VK, PJM, MEC, KBW, CGC and CGK, report no competing interests. REG and BIT report unrelated investigator-initiated research support from AstraZeneca Pharmaceuticals and Pfizer Inc.
Funding Information:
This study was funded in part by National Institutes of Health Grants MH63381 (PJM), K08MH79364 (MEC), and K23MH079498 (KBW). The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2012/7
Y1 - 2012/7
N2 - 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',5'-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.
AB - 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',5'-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.
KW - Adenosine cyclase
KW - CAMP
KW - DISC1
KW - Schizophrenia prodrome
KW - Ultra high risk
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U2 - 10.1016/j.schres.2012.03.029
DO - 10.1016/j.schres.2012.03.029
M3 - Article
C2 - 22537567
AN - SCOPUS:84862137814
VL - 138
SP - 280
EP - 284
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
IS - 2-3
ER -