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

Abstract

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.

Olfactory Dysfunction in Children: A Scoping Review

“…[23][24][25][26][27][28] The most common congenital etiology by number of cases was 22q11.2 deletion syndrome with 98 total cases reported from 3 studies. 8,29,30 The most common etiology by number of reports was Kallmann syndrome (including its associations) with 24 studies describing a total of 64 cases. Reported etiologies have been categorized into whether the mechanism is hypothesized to be sensorineural, conductive, or mixed.…”

“…As well, 6 studies described olfactory loss associated with autism spectrum disorder, accounting for 126 cases 23‐28 . The most common congenital etiology by number of cases was 22q11.2 deletion syndrome with 98 total cases reported from 3 studies 8,29,30 . The most common etiology by number of reports was Kallmann syndrome (including its associations) with 24 studies describing a total of 64 cases 31‐54 …”

Neuropsychiatric Symptoms Mediated the Relationship Between Odor Identification and Cognition in Alzheimer's Disease Spectrum: A Structural Equation Model Analysis

“…Similar to affective symptoms, psychosis symptoms also had a partial mediated effect on the relationship between cognitive function and odor identification. Previous research indicates that odor identification dysfunction is present in schizophrenia patients (Moberg et al, 2006 ), first-degree relatives of schizophrenia patients (Turetsky et al, 2008 ), and subjects at risk for psychosis symptoms (Takahashi et al, 2018 ; Tang et al, 2018 ) and is believed to be highly associated with disease duration (Moberg et al, 2006 ), negative symptoms, and social-cognitive function (Corcoran et al, 2005 ). The anatomic proximity of the olfactory network to limbic structures provides a potential explanation for the relation between olfaction and affective symptoms, and may account for their shared dysfunction in various psychiatric disorders.…”

Recent developments in understanding the relationship between 22q11.2 deletion syndrome and psychosis

“…Tang et al [11] conducted a pilot study of 32 individuals to examine olfactory functioning as a possible biomarker for psychosis in 22q11.2DS. They showed that both odour identification and discrimination are significantly impaired in individuals with 22q11.2DS compared to healthy controls.…”