Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia

Abstract

There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.

Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis

“… 58 A small Polish case–control study showed nominal significance ( P =0.03) for a functional SNP (T29C; Leu10Pro 59 ) being associated with schizophrenia. 60 In the Polish study, TGFB1 protein was also upregulated in schizophrenia cases versus controls, 60 consistent with our findings of increased messenger RNA expression in schizophrenia cases.…”

Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia

“…Genetic variants in TGFB1 gene affect susceptibility to schizophrenia. TGF-β signaling might be a valid link contributing to schizophrenia patients [56, 57]. NDUFA10 has been contributed to the abnormalities of mitochondrial function in schizophrenia [58].…”

Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines

“…It is thus important to consider how the demographics of the subjects studied here may have influenced the observations made. No difference has been observed in circulating levels of TGF-b 1 in male and female subjects in prior studies (79,97,98), but differences have been reported in subjects of differing ethnicity, with higher circulating TGF-b 1 observed in black compared to white ethnic groups (99). However, although the chronicallyinfected subjects studied here were predominantly Caucasian, plasma TGF-b 1 levels in chronically HIV-1-infected subjects were also found to be higher than those in seronegative controls in another study where all participants were of black African ethnicity (51), and similar observations were also made in a study focusing on a relatively mixed group of Caucasian, Asian and black subjects (53).…”