Smell Impairmet and Schizophrania: Genotypic and Phenotypc Correlates in a Familial Cohort

Background Schizophrenia is a mental disorder in which patients experience altered perception of the world. It has been reported to manifest in smell impairment similar to other neuropsychiatric and neurodegenerative disorders. The sense of smell functions through olfactory receptor genes (ORs), a large family of G protein coupled receptors (GPCR), however, how it relates to neurotransmitters dysfunction associated with schizophrenia remains largely speculative. Methods Based on preliminary findings of ORs enrichment in whole genomes/exomes of seven families with multiple siblings affected with schizophrenia, sequence data were further interrogated focusing this time on ORs genes. A separate study using 10 different odorants was carried out in 116 healthy controls, 24 patients and 18 healthy first degree relatives, to test their olfactory identification and detection abilities. Results and Discussion In concordance with the literature, there were significant differences between schizophrenia cases and population healthy controls in smell identification rather than total detection with P ≤ 0.001. Although no single variant was found shared between all seven families, several pathogenic variants were shared between two families or more, with marked enrichment in chromosome 11. Four rare variants were detected in one family together with eight rather common variants associated with sensory perception .Network analysis showed centrality of olfactory and non-ORs genes like Sonic Hedgehog (SHH) signaling pathway which may shed light on possible functional aspects of the OR impairment in schizophrenia. Conclusion The implication of these findings and the marked inter familial variation warrants further investigation of smell impairment involvement in schizophrenia pathogenesis in both individualized and globalized settings.