RT Journal Article SR Electronic T1 TGF-β1 is associated with deficits in cognition and cerebral cortical thickness in first-episode schizophrenia JF Journal of Psychiatry and Neuroscience JO JPN FD Canadian Medical Association SP E86 OP E98 DO 10.1503/jpn.210121 VO 47 IS 2 A1 Shujuan Pan A1 Yanfang Zhou A1 Ling Yan A1 Fangling Xuan A1 Jinghui Tong A1 Yanli Li A1 Junchao Huang A1 Wei Feng A1 Song Chen A1 Yimin Cui A1 Fude Yang A1 Shuping Tan A1 Zhiren Wang A1 Baopeng Tian A1 L. Elliot Hong A1 Yun-Long Tan A1 Li Tian YR 2022 UL http://jpn.ca/content/47/2/E86.abstract AB Background: Evidence indicates that cytokines are associated with cognitive deficits in schizophrenia; however, the underlying brain–behaviour mechanisms remain unclear. We hypothesized that aberrations in brain structural connectivity mediate the cytokine effect in schizophrenia.Methods: In this study, we recruited patients with first-episode schizophrenia (n = 75, average illness duration 12.3 months, average medication period 0.6 days) and healthy controls (n = 44) of both sexes. We first conducted whole-blood RNA sequencing to detect differentially expressed genes. We also explored transcriptomic data on the dorsal lateral prefrontal cortices (dlPFC) retrieved from the CommonMind Consortium for gene functional clustering; we measured plasma transforming growth factor β1 (TGF-β1) levels by enzyme-linked immunosorbent assay; we acquired high-resolution T1-weighted MRI data on cortical thickness MRI; and we assessed cognitive function using the validated Chinese version of the MATRICS Consensus Cognitive Battery. We compared these parameters in patients with schizophrenia and controls, and analyzed their associations.Results: Patients with schizophrenia had higher TGF-β1 at both the mRNA level (log2 fold change = 0.24; adjusted p = 0.026) and the protein level (12.85 ± 6.01 μg/mL v. 8.46 ± 5.15 μg/mL, adjusted p < 0.001) compared to controls. Genes coexpressed with TGFB1 in the dlPFC were less abundant in patients with schizophrenia compared to healthy controls. In patients with schizophrenia, TGF-β1 protein levels were inversely correlated with cortical thickness, especially of the lateral occipital cortex (r = −0.47, adjusted p = 0.001), and with the MATRICS Consensus Cognitive Battery visual learning and memory domain (r = −0.50, adjusted p < 0.001). We found a complete mediation effect of the thickness of the lateral occipital cortex on the negative relationship between TGF-β1 and visual cognition (p < 0.05).Limitations: We did not explore the effect of other blood cytokines on neurocognitive performance and cortical thickness. Participants from the CommonMind Consortium did not all have first-episode schizophrenia and they were not all antipsychotic-naive, so we could not exclude an effect of antipsychotics on TGF-β1 signalling in the dlPFC. The sample size and cross-sectional design of our study were additional limitations.Conclusion: These findings highlighted an association between upregulated blood levels of TGF-β1 and impairments in brain structure and function in schizophrenia.