Olfactory function, transcranial sonography and fear generalization in patients with 22q11.2 deletion syndrome along the lifespan

Introduction The 22q11.2 deletion syndrome (22q11.2DS) is a rare chromosomal syndrome with a prevalence of approximately 0.025%. Affected individuals show a wide range of somatic features, most commonly congenital heart defects, immunodeficiency, hypoparathyroidism and palatal abnormalities. Furthermore, the syndrome is highly comorbid with psychiatric disorders. Among potential biomarkers in a range of modalities are substantia nigra (SN) hyperechogenity (reported in adult 22q11.2DS) and compromised olfactory function (reported in pediatric 22q11.2DS). Regarding fear conditioning and fear generalization, there is a scarcity of research despite the high number of comorbid anxiety disorders.

Methods We performed a multimodal assessment of olfactory function and transcranial sonography (TCS) on a sample of N = 39 22q11.2DS patients and N = 39 age and sex-matched healthy controls (age 4 – 44 years, m = 14.8 ± 8; N = 16 female). SN echogenicity was quantified with a planimetric measurement of the hyperechogenic signal at the location of the SN in mm². Olfactory sensitivity and discrimination was assessed with the Sniffin Sticks kit. For the assessment of fear learning and generalization, we used the paradigm established within the framework of SFB TRR58.

Results We found lower olfactory sensitivity (p < .001) and discrimination (p < .001) in 22q11.2DS compared to controls. ADHD symptoms correlated positively (p = .034) and symptoms of schizophrenia correlated negatively with olfactory discrimination (p = .005). There were no differences in SN echogenicity (p = .316). Preliminary data furthermore indicate altered fear generalization in 22q11.2DS.

Conclusion The results of our study point towards stable differences in olfactory functioning in 22q11.2DS, whereas we could not replicate previous findings of abnormal SN echogenicity. A combination of endophenotypes may be promising in characterizing the syndrome.