An odor-specific threshold deficit implicates abnormal intracellular cyclic AMP signaling in schizophrenia
Bruce I Turetsky1, Paul J Moberg
1Department of Psychiatry, University of Pennsylvania, 10th Floor, Gates Building, 3400 Spruce St., Philadelphia, PA 19104, USA. turetsky@upenn.edu
The American Journal of Psychiatry
|December 17, 2008
Summary
Schizophrenia patients and their relatives show impaired odor detection, suggesting a genetically mediated disruption in cyclic adenosine monophosphate (cAMP) signaling, a key pathway in olfactory neurons.
Area of Science:
- Neuroscience
- Genetics
- Olfactory Research
Background:
- Olfactory deficits are prevalent in schizophrenia, but their biological basis is unclear.
- Cyclic adenosine monophosphate (cAMP) signaling is crucial for olfactory receptor neuron function and may be disrupted in schizophrenia.
Purpose of the Study:
- To investigate the hypothesis that disrupted cAMP signaling contributes to olfactory deficits in schizophrenia.
- To assess odor detection sensitivities in schizophrenia patients, relatives, and controls using odorants with differential cAMP activation.
Main Methods:
- Odor detection threshold sensitivities were measured for citralva (strong cAMP activator) and lyral (weak cAMP activator) in 30 schizophrenia patients, 25 healthy controls, and 19 unaffected relatives.
- Statistical analysis examined group-by-odor interactions, controlling for age, sex, smoking, symptoms, and medication.
Main Results:
- A significant group-by-odor interaction was observed.
- Schizophrenia patients and unaffected relatives exhibited impaired detection of lyral compared to citralva.
- Healthy controls showed equal sensitivity to both odorants, indicating an odor-specific deficit.
Conclusions:
- The findings suggest an odor-specific hyposmia in schizophrenia, indicative of dysregulated cAMP-mediated signal transduction.
- The parallel deficit in unaffected relatives points to a genetically mediated component of this olfactory dysfunction.
- These results provide strong inferential evidence for impaired cAMP signaling in schizophrenia pathophysiology.
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