Peripheral blood neuroendocrine hormones are associated with clinical indices of sport-related concussion

Abstract

The purpose of this study was to evaluate the relationship between neuroendocrine hormones and clinical recovery following sport-related concussion (SRC). Ninety-five athletes (n = 56 male, n = 39 female) from a cohort of 11 interuniversity sport teams at a single institution provided blood samples; twenty six athletes with SRC were recruited 2-7 days post-injury, and 69 uninjured athletes recruited prior to the start of their competitive season. Concentrations of seven neuroendocrine hormones were quantitated in either plasma or serum by solid-phase chemiluminescent immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms at the time of blood sampling in all athletes. Multivariate partial least squares (PLS) analyses were used to evaluate the relationship between blood hormone concentrations and both (1) time to physician medical clearance and (2) initial symptom burden. A negative relationship was observed between time to medical clearance and both dehydroepiandrosterone sulfate (DHEA-S) and progesterone; a positive relationship was found between time to medical clearance and prolactin. Cognitive, somatic, fatigue and emotion symptom clusters were associated with distinct neuroendocrine signatures. Perturbations to the neuroendocrine system in athletes following SRC may contribute to initial symptom burden and longer recovery times.

Figure 1

Athlete enrollment from objective measures of sport concussion project, and study participant selection. *One subject removed due to missing symptoms, and one subject removed due to missing values in five of seven hormones. **Thirteen subjects were removed due to subsequent concussion and recruitment in the SRC group; 28 subjects were excluded because they had their blood drawn prior to 11am; 45 subjects were removed because they had exercised within 24 h; 10 subjects were excluded due to repeated enrollment in subsequent years (only a single enrolment per subject was allowed).

Figure 2

Correlation between neuroendocrine hormones and days to medical clearance. Thyroid stimulating hormone (TSH), free thyroxine (FT4), dehydroepiandrosterone sulfate (DHEA-S), and adrenocorticotropic Hormone (ACTH). Plot shows the correlations between neuroendocrine hormones measured in the subacute period following sport-related concussion (SRC) and days to medical clearance by partial least squares (PLS) analysis. Bars represent biomarker loadings and standard errors derived from bootstrapped resampling (5000 samples). Green bars = significant at a false discovery rate (FDR) < 0.05.

Figure 3

Correlation between neuroendocrine hormones and symptom clusters. Adrenocorticotropic Hormone (ACTH), (DHEA-S), free thyroxine (FT4), thyroid stimulating hormone (TSH). Plots show the correlations between neuroendocrine hormones measured in the subacute period following sport-related concussion and (A) somatic symptoms, (B) cognitive symptoms, (C) fatigue symptoms, and (D) emotion symptoms, by partial least squares (PLS) analysis. Bars represent biomarker loadings and standard errors derived from bootstrapped resampling (5000 samples). Green bars = significant correlation with days to recovery at a false discovery rate (FDR) <0.05.