title: Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia.
abstract: BACKGROUND
  Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia.
  
  
  METHODS
  To examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women.
  
  
  RESULTS
  On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls.
  
  
  CONCLUSIONS
  Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed.
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA. Electronic address: Josh.Woolley@ucsf.edu.
authors: J D
authors: JD
authors: Woolley
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors: O
authors: O
authors: Lam
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors: B
authors: B
authors: Chuang
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors: J M
authors: JM
authors: Ford
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors: D H
authors: DH
authors: Mathalon
authors: Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors: S
authors: S
authors: Vinogradov
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000447:Aldehydes; D016022:Case-Control Studies; D018592:Cross-Over Studies; D000242:Cyclic AMP; D053138:Cyclohexenes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000857:Olfaction Disorders / Q000150:complications / Q000188:drug therapy*; D010120:Oxytocics / Q000494:pharmacology / Q000627:therapeutic use*; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications*; D012684:Sensory Thresholds / Q000187:drug effects; D015398:Signal Transduction; D012903:Smell / Q000187:drug effects; D055815:Young Adult
chemical_list: D000447:Aldehydes; D053138:Cyclohexenes; D010120:Oxytocics; D010121:Oxytocin; D000242:Cyclic AMP; C092244:hydroxyisohexyl 3-cyclohexene carboxaldehyde
keywords: Olfaction; Oxytocin; Schizophrenia
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