title: An odor-specific threshold deficit implicates abnormal cAMP signaling in youths at clinical risk for psychosis.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. kamathv@upenn.edu
authors.forename: Vidyulata
authors.initials: V
authors.lastname: Kamath
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Moberg
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.forename: Karin
authors.initials: K
authors.lastname: Borgmann-Winter
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Conroy
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Christian G
authors.initials: CG
authors.lastname: Kohler
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
mesh_terms: D000293:Adolescent; D000447:Aldehydes; D002450:Cell Communication / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D053138:Cyclohexenes; D005260:Female; D006801:Humans; D008297:Male; D009570:Nitriles; D009812:Odorants; D000857:Olfaction Disorders / Q000150:complications / Q000503:physiopathology*; D055696:Olfactory Perception / Q000502:physiology*; D011618:Psychotic Disorders / Q000150:complications / Q000503:physiopathology*; D012306:Risk; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology; D012684:Sensory Thresholds / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D000447:Aldehydes; D053138:Cyclohexenes; D009570:Nitriles; C054764:citralva; D000242:Cyclic AMP; C092244:hydroxyisohexyl 3-cyclohexene carboxaldehyde