Exploratory Biological Correlates of Cognitive and Language Performance in Healthy Pubertal Children: A Retrospective Cross-Sectional Study

Abstract

Background/Objectives: Adolescence is a dynamic neurodevelopmental period during which structured language performance may reflect ongoing biological reorganization processes. This study examined whether inflammatory, nutritional, and hormonal biomarkers were modestly associated with structured language task performance and cognitive performance in healthy pubertal children. Methods: A total of 156 healthy pubertal children (78 female, 78 male; mean age of 11.84 ± 2.98 years) meeting Tanner Stage ≥ 2 were included in this retrospective cross-sectional study. Language was assessed with the Test of Language Development-Primary: Fourth Edition (TOLD-P:4; Turkish adaptation) and cognition with the Wechsler Intelligence Scale for Children-Revised (WISC-R). Pan-Immune-Inflammation Value (PIV), Prognostic Nutritional Index (PNI), Neutrophil-to-Lymphocyte Ratio (NLR), vitamin B12, 25-OH vitamin D, ferritin, and TSH were included as biomarkers. Two-block hierarchical OLS regression and Spearman correlations with Benjamini–Hochberg FDR correction were used. Results: The biomarker block provided a statistically significant incremental contribution to the spoken language model (ΔR2 = 0.066, p = 0.041; full model R2 = 0.287). The primary test statistic was ΔR2. In exploratory coefficient-level analyses that were not corrected for multiple comparisons, the PIV (β = +0.17, p = 0.033) and TSH (β = −0.17, p = 0.031) coefficients reached nominal significance. After FDR correction, PIV was positively associated with WISC-R Verbal score (ρ = +0.24, p_FDR = 0.019) and TSH negatively with TOLD-P:4 Speaking (ρ = −0.22, p_FDR = 0.029). Biomarker contribution to WISC-R Full-Scale IQ was non-significant (ΔR2 = 0.049, p = 0.223). Conclusions: At the block level, the biomarker set contributed significantly to the structured spoken-language model but not to the Full-Scale IQ model; however, one of the two FDR-significant bivariate associations involved a verbal cognitive measure (PIV with WISC-R Verbal). Any language-versus-cognition contrast should therefore be interpreted cautiously. The modest effect sizes suggest these relationships are best interpreted within a developmental and neuroimmune framework. Longitudinal and multimodal studies are needed to replicate these findings. Because the TOLD-P:4/TODİL was applied beyond its validated age range (4; 0–8; 11) and its cross-age scoring could not be verified from the retrospective records, all language-based findings are exploratory and require confirmation with an age-validated instrument; the study’s confirmatory finding is the FDR-significant association of PIV with age-appropriate WISC-R Verbal performance. Because the TOLD-P:4/TODİL composite scores could not be verified as comparable across the sample’s age range, all TOLD-P:4-based results reported here are exploratory and hypothesis-generating; the confirmatory analyses rely on the age-appropriate WISC-R outcomes.