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Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome.

Olfactory functioning is a promising biomarker for psychosis in 22q11.2 deletion syndrome (22q11DS) but has not been well studied to date. This is a pilot effort to evaluate the potential for tests of olfactory functioning to contribute to risk and resilience prediction in 22q11DS, and is the first study to evaluate relationships among olfactory deficits, cognition and psychosis-spectrum symptoms. Odor identification and discrimination were evaluated in 32 individuals with 22q11DS and 110 healthy comparison subjects (HC). Individuals with 22q11DS also underwent cognitive testing with the Penn Computerized Neurocognitive Battery, which evaluates executive functioning, episodic memory, complex cognition, and social cognition. Positive, negative, disorganized and general psychosis-spectrum symptoms were rated according to the Scale of Prodromal Symptoms. Age-normalized scores were calculated for odor identification and discrimination based on normative data. Both odor identification (p < 0.001, Cohen's d = -2.15, 95% CI [-2.62, -1.68]) and discrimination (p < 0.001, Cohen's d = -1.81, 95% CI [-2.26, -1.35]) were significantly impaired in 22q11DS relative to HC. There were no sex differences in either group. Neither odor identification nor discrimination was correlated with overall cognition or any specific cognitive domain in 22q11DS. Impairment in odor discrimination was correlated with higher negative and overall psychosis-spectrum symptoms. There was no significant effect of catechol-O-methyltransferase Val(158)Met genotype or presence of velopharyngeal insufficiency on olfactory functioning. Olfactory deficits, particularly olfactory discrimination, are robust in 22q11DS and appear to be independent of cognitive deficits. They are also clinically relevant and related to psychosis-spectrum symptoms. Olfactory functioning appears to be a promising biomarker for psychosis in 22q11DS.

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