Association of serum BMP2 with delayed memory impairment in first-episode, drug-naïve schizophrenia
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FEDN patients had significantly elevated serum BMP2 and BMP9 versus controls after adjustment (p = 0.015 and p = 0.004).
Higher serum BMP2 was negatively associated with RBANS delayed memory in patients, explaining a modest 7% of variance (partial R2 = 0.071).
Cross sectional design and small effect size limit causal inference; findings are hypothesis generating and require replication in larger longitudinal multicentre studies.
BACKGROUND: Cognitive impairments, particularly in the domain of memory, are core and enduring features of schizophrenia. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-β superfamily, are involved in neurodevelopment and synaptic plasticity, but few studies have investigated their relevance to cognitive deficits in schizophrenia.
METHODS: In this study, we measured circulating levels of BMP2, BMP9, and BMP10, and evaluated correlations with cognitive performance and psychopathological symptoms among first-episode, drug-naïve (FEDN) patients with schizophrenia. Ninety FEDN patients were assessed for psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS). Patients and ninety demographically matched healthy controls (HCs) also completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and provided serum samples for Luminex-based BMP assays.
RESULTS: After covariate adjustment, patients exhibited significantly elevated serum BMP2 (p = 0.015) and BMP9 (p = 0.004) concentrations. Within the patient group, higher serum BMP2 was significantly negatively associated with RBANS delayed memory (RBANS-DM) scores after adjustment for demographic and clinical covariates (β = -0.236, p = 0.014), accounting for a modest 7% of variance (partial R2 = 0.071). No robust associations of BMP9 or BMP10 with cognitive domains or symptoms were detected beyond exploratory trend-level findings.
CONCLUSIONS: These results suggest a potential association between elevated serum BMP2 and poorer delayed memory performance in early-stage schizophrenia. Given the cross-sectional design and modest effect size, the findings should be interpreted as hypothesis-generating rather than causal. BMP2 may represent a candidate peripheral correlate of delayed memory performance, warranting replication in larger, longitudinal, multicenter studies.
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