Structural brain network alterations in schizophrenia and ultra-high risk populations: Linking olfactory dysfunction to clinical symptoms.
Olfactory dysfunction is an early feature of schizophrenia, but its structural brain network basis remains unclear, especially in ultra-high risk (UHR) individuals.
We recruited 99 drug-naive first-episode schizophrenia patients (FES), 72 UHR individuals (followed for 2 years), and 69 healthy controls individuals (HC). Olfactory function was assessed by using the Odor Stick Identification Test for the Japanese (OSIT-J). Structural MRI data were processed to measure cortical volume and thickness across 8 brain networks. General linear models and partial correlation analyses were conducted. Mediation analysis assessed whether brain network alterations mediated the relationship between olfactory function and symptoms. Logistic regression assessed psychosis conversion in UHR.
Both FES and UHR groups exhibited reduced OSIT-J scores and decreased brain network volumes compared to that of the HC group (p-FDR < 0.05), with the default mode network (DMN) and frontoparietal network (FPN) showing the strongest associations with olfactory performance. Mediation analysis revealed that DMN and FPN volumes mediated the relationship between olfactory impairment and clinical symptoms in both FES and UHR. Poorer OSIT-J scores predicted psychosis conversion in UHR (OR = 0.35, p = 0.009), with the combined OSIT-J and intracranial volume model achieving high predictive accuracy (AUC = 0.86).
Olfactory impairment is closely linked to structural alterations in DMN and FPN, which mediate its impact on symptoms. When combined with structural brain measures, the OSIT-J may contribute to risk assessment of UHR transition to schizophrenia.
We recruited 99 drug-naive first-episode schizophrenia patients (FES), 72 UHR individuals (followed for 2 years), and 69 healthy controls individuals (HC). Olfactory function was assessed by using the Odor Stick Identification Test for the Japanese (OSIT-J). Structural MRI data were processed to measure cortical volume and thickness across 8 brain networks. General linear models and partial correlation analyses were conducted. Mediation analysis assessed whether brain network alterations mediated the relationship between olfactory function and symptoms. Logistic regression assessed psychosis conversion in UHR.
Both FES and UHR groups exhibited reduced OSIT-J scores and decreased brain network volumes compared to that of the HC group (p-FDR < 0.05), with the default mode network (DMN) and frontoparietal network (FPN) showing the strongest associations with olfactory performance. Mediation analysis revealed that DMN and FPN volumes mediated the relationship between olfactory impairment and clinical symptoms in both FES and UHR. Poorer OSIT-J scores predicted psychosis conversion in UHR (OR = 0.35, p = 0.009), with the combined OSIT-J and intracranial volume model achieving high predictive accuracy (AUC = 0.86).
Olfactory impairment is closely linked to structural alterations in DMN and FPN, which mediate its impact on symptoms. When combined with structural brain measures, the OSIT-J may contribute to risk assessment of UHR transition to schizophrenia.
Authors
Peng Peng, He He, Chen Chen, Chen Chen, Li Li, Li Li, Jin Jin, Yuan Yuan, Ma Ma
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