Disrupted small-world networks in children with drug-naïve growth hormone deficiency: a DTI-based network analysis

Growth hormone deficiency (GHD) in children results from impairment of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. Although GHD's effects on brain structure and function have been studied, its impact on large-scale white matter (WM) structural connectivity remains poorly understood. We aimed to investigate the topological organization of WM structural connectome in pediatric GHD using diffusion tensor imaging (DTI) and graph theoretical analysis.

This cross-sectional study included 58 drug-naïve children with GHD and 30 typically developing (TD) controls matched for age and gender. DTI data were analyzed using deterministic tractography, and the structural connectivity between 90 cortical and subcortical regions was assessed. Graph theoretical analysis was applied to evaluate topological parameters of the resulting graphs. Between-group comparison of networks metrics was assessed. Finally, a partial correlation analysis was performed to explore the relationship between significant topologic metrics and clinical symptom severity.

Compared to TD groups, the GHD patients showed altered global properties, including increased characteristic path length (P<0.001), and decreased global (P<0.001) and local efficiency (P<0.001). Regarding nodal parameters, GHD showed abnormal nodal parameters (nodal degree, efficiency, betweenness) primarily in regions associated with the default mode network (DMN), central executive network (CEN), visual network (VN), salience network (SN), sensorimotor network (SMN), basal ganglia, and left thalamus. Besides, the scores of Achenbach's Child Behavior Check List (CBCL) of GHD was positively correlated with the nodal efficiency in the left middle occipital gyrus (P=0.048, uncorrected), right inferior parietal lobe (P=0.035, uncorrected), and left middle temporal gyrus (r=0.295; P=0.034, uncorrected).

Our findings reveal disrupted WM topological organization in children with GHD, which may potentially relate to abnormal GH/IGF-1 levels and associated with behavioral problems. These alterations in structural brain networks may underlie the behavioral challenges observed in GHD, providing new insights into the neurobiological basis of this condition.