Olfactory Identification in 7-Year-Old Children with Familial High Risk of Schizophrenia or Bipolar Disorder - The Danish High Risk and Resilience Study VIA 7

Abstract

Background: Olfactory identification deficits are present in individuals with schizophrenia and their unaffected first-degree relatives, while deficits are less pronounced in individuals with bipolar disorder. We hypothesized that children with familial high-risk for schizophrenia (FHR-SZ) show olfactory identification deficits compared to population-based controls (PBC), and that children with familial high-risk for bipolar disorder (FHR-BP) perform intermediate. Furthermore, we investigated potential relationships with psychopathology, cognition, and home environment. Methods: Olfactory identification was assessed at age 7 in 184 children with FHR-SZ, 106 children with FHR-BD, and 186 PBC with the Brief Smell Identification Test (BSIT). BSIT total score and the proportion of children scoring below pre-defined cut-off scores were the outcomes. Potential relationships with psychopathological, cognitive, and home environmental variables were conducted using hierarchical and logistic multiple regression analyses. Outcomes: ANOVA revealed no between-group differences in olfactory identification. Chi-square test of independence showed a significant greater proportion of boys with FHR-SZ than population-based boys with an abnormal olfactory identification (p<0·05). Regression analyses of all children showed significant positive associations of olfactory identification with girls, social responsiveness, and working memory. Less social responsiveness predicted abnormal olfactory identification in boys with FHR-SZ. Interpretation: Abnormal olfactory identification is more frequent in 7-year-old boys with FHR-SZ than in matched low-risk boys and is linked to a deficit of social responsiveness. This supports the idea that olfactory and social dysfunction share a common pathophysiological and perhaps neurobiological pathway in schizophrenia. Funding Statement: Mental Health Services of the Capital Region of Denmark, Aarhus University, and the Lundbeck Foundation Initiative for Integrative Psychiatric Research. Declaration of Interests: All authors confirmed to have no conflicts of interest. Ethics Approval Statement: The project was approved by The Danish Data Protection Agency. The study procedures were aligned with the guidelines of the National Committee for Health Research Ethics, although formal ethical approval was not required due to its observational design.