Altered olfactory processing in schizophrenia: a sensory signature of clinical severity

Introduction Schizophrenia is a psychiatric disorder characterized by positive symptoms, negative symptoms and cognitive impairments. Increasing evidence indicates that sensory processing abnormalities represent a fundamental aspect of the disorder, particularly olfactory dysfunction. Aim This study investigated olfactory performance in patients with treatment-resistant schizophrenia (TRS), patients with treatment-responsive schizophrenia (SCZ), and healthy controls. Methods This cross-sectional, non-interventional study was conducted over six months and included three groups: TRS patients (n = 27), SCZ patients (n = 23), and healthy controls (n = 21). Inclusion criteria were DSM-5 diagnosis of schizophrenia and age 18–65 years. Exclusion criteria included substance use within the past six months, major neurological or medical conditions, history of headtrauma, recent upper respiratory infections, severe sensory impairments, and intellectual disability. Collected variables included age, sex, age at onset, illness duration, smoking status, and current pharmacological treatment. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning with the Brief Assessment of Cognition in Schizophrenia (BACS). Olfactory performance was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Participants also provided valence ratings for each odor (pleasant, neutral, unpleasant). Results Post-hoc Mann–Whitney U tests with Bonferroni correction (adjusted α = .017) showed that both TRS and SCZ patients performed significantly worse than healthy controls (TRS vs CTRL: U =44.5, p < .001, r = .83; SCZ vs CTRL: U = 82.5, p < .001, r = .62). No difference was observed between TRS and SCZ (U = 394.0, p = .106, r = –.27). Smoking was not associated with olfactory performance (UPSIT vs cigarettes/day: ρ = –0.089, p = 0.467). Subscore analysis revealed aspecific impairment for neutral odors. The Neutral subscore showed a strong group effect (p <.001), with both TRS and SCZ scoring significantly lower than controls (TRS vs CTRL: U = 9.0, p< .001, r = .87; SCZ vs CTRL: U = 7.0, p = .002, r = .88), while no difference emerged between clinical groups (U = 394.0, p = .059). No significant group differences were found for pleasant orunpleasant odors. Across the whole sample, UPSIT total score was negatively correlated withillness duration (ρ = –.287, p = .043). Significant negative correlations were also observed with PANSS total (ρ = –.381, p = .006), PANSS negative (ρ = –.462, p < .001), PANSS disorganization (ρ = –.472, p < .001), and PANSS positive (ρ = –.332, p = .018). Regarding cognition, UPSIT performance showed significant positive correlations with Tower of London (p = .009), verbal memory (p = .019), and symbol coding (p = .026). Conclusion Olfactory dysfunction may represent one of the features associated with schizophrenia, and is also linked to symptom severity. It is associated with symptom severity, illness duration, and cognitive impairment, supporting its potential role as a non-invasive marker of disease severity and clinical status.

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