Olfactory Deficits and Structural Anomalies of the Peripheral Olfactory System in 22q11.2 Deletion Syndrome
- 1University of Pennsylvania
Abstract
Background: Approximately 25% of individuals with 22q11.2 deletion syndrome (22q11DS) develop a psychotic disorder, and the syndrome shares key neurodevelopmental features with psychosis in the general population. The olfactory system develops early in utero, providing a window into gestational disruptions relevant to psychosis risk. We hypothesized that 22q11DS would show impairments in olfactory function and structural anomalies of the olfactory system relative to psychosis spectrum (PS) youth without a known genetic syndrome and typically developing controls (TD). Methods: Participants included individuals with 22q11DS (n=101), PS (n=56), and TD (n=52). Sinonasal symptoms, odor identification, and discrimination (Sniffin' Sticks) behaviorally. Structural 3T MRI measured olfactory bulb volume, sulcus depth, and sulcus length. Sample sizes vary per analysis. Results: Relative to TD, 22q11DS showed elevated sinonasal burden (p<.001), lower odor identification (p<.001), and lower odor discrimination (p<.001). PS showed elevated sinonasal burden (p<.001) and marginally lower odor identification (p=.06), but no discrimination deficit. Olfactory bulb volume was significantly smaller in 22q11DS versus TD (p=.007, r=.39); PS showed a non-significant trend (p=.07). Olfactory sulcus depth (p=.52) and length (p=.82) did not differ across groups. Conclusions: 22q11DS is associated with elevated sinonasal burden, robust olfactory identification and discrimination deficits exceeding those of PS and reduced olfactory bulb volume. The co-occurrence of functional deficits and reduced bulb volume without sulcal anomalies may distinguish the 22q11DS olfactory phenotype from that of PS. These hypothesis-generating findings are consistent with partially dissociable neurodevelopmental mechanisms and support the utility of 22q11DS as a genetic model for psychosis risk.
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BibTeX
@misc{roalf2026olfactory,
title = {{Olfactory Deficits and Structural Anomalies of the Peripheral Olfactory System in 22q11.2 Deletion Syndrome}},
author = {D. R. Roalf and D. M. McDonald-McGinn and A. Atkins and M. E. Calkins and T. B. Crowley and P. Freedman and R. S. Gallagher and C. Mastracchio and D. E. McGinn and A. Moran and A. Olson and M. K. Pecsok and L. Rockart and O. Tran and E. H. Zackai and B. S. Emanuel and K. Ruparel and R. T. Shinohara and L. K. White and J. E. Schmitt and R. E. Gur},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756775},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756775v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Olfactory Deficits and Structural Anomalies of the Peripheral Olfactory System in 22q11.2 Deletion Syndrome
AU - D. R. Roalf
AU - D. M. McDonald-McGinn
AU - A. Atkins
AU - M. E. Calkins
AU - T. B. Crowley
AU - P. Freedman
AU - R. S. Gallagher
AU - C. Mastracchio
AU - D. E. McGinn
AU - A. Moran
AU - A. Olson
AU - M. K. Pecsok
AU - L. Rockart
AU - O. Tran
AU - E. H. Zackai
AU - B. S. Emanuel
AU - K. Ruparel
AU - R. T. Shinohara
AU - L. K. White
AU - J. E. Schmitt
AU - R. E. Gur
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756775
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756775v1
AB - Background: Approximately 25% of individuals with 22q11.2 deletion syndrome (22q11DS) develop a psychotic disorder, and the syndrome shares key neurodevelopmental features with psychosis in the general population. The olfactory system develops early in utero, providing a window into gestational disruptions relevant to psychosis risk. We hypothesized that 22q11DS would show impairments in olfactory function and structural anomalies of the olfactory system relative to psychosis spectrum (PS) youth without a known genetic syndrome and typically developing controls (TD). Methods: Participants included individuals with 22q11DS (n=101), PS (n=56), and TD (n=52). Sinonasal symptoms, odor identification, and discrimination (Sniffin' Sticks) behaviorally. Structural 3T MRI measured olfactory bulb volume, sulcus depth, and sulcus length. Sample sizes vary per analysis. Results: Relative to TD, 22q11DS showed elevated sinonasal burden (p<.001), lower odor identification (p<.001), and lower odor discrimination (p<.001). PS showed elevated sinonasal burden (p<.001) and marginally lower odor identification (p=.06), but no discrimination deficit. Olfactory bulb volume was significantly smaller in 22q11DS versus TD (p=.007, r=.39); PS showed a non-significant trend (p=.07). Olfactory sulcus depth (p=.52) and length (p=.82) did not differ across groups. Conclusions: 22q11DS is associated with elevated sinonasal burden, robust olfactory identification and discrimination deficits exceeding those of PS and reduced olfactory bulb volume. The co-occurrence of functional deficits and reduced bulb volume without sulcal anomalies may distinguish the 22q11DS olfactory phenotype from that of PS. These hypothesis-generating findings are consistent with partially dissociable neurodevelopmental mechanisms and support the utility of 22q11DS as a genetic model for psychosis risk.
ER -