The ratio of GABA/Glu as a biomarker in children with attention deficit hyperactivity disorder
Xue Cheng1, Lingzhi Wang1, Cong Diao1
1Pediatrics Department, Zibo Central Hospital, No. 10 Shanghai Road, Zhangdian District, Zibo, 255000, Shandong, China.
Background:
Attention-deficit/hyperactivity disorder (ADHD) lacks objective laboratory biomarkers for diagnosis and disease monitoring. Given the potential role of excitatory-inhibitory imbalance in ADHD pathophysiology, this study investigated the clinical significance of serum gamma-aminobutyric acid (GABA), glutamate (Glu), and the GABA/Glu ratio in children with ADHD.
Methods:
A total of 145 children with ADHD and 120 healthy controls were enrolled. Serum GABA and Glu levels were measured by ultra-performance liquid chromatography-tandem mass spectrometry, and the GABA/Glu ratio was calculated. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic performance. Correlations between neurotransmitter indicators and SNAP-IV subscale scores were analyzed in the ADHD group. In addition, changes in serum GABA, Glu, and GABA/Glu ratio were evaluated after 12 weeks of methylphenidate treatment.
Result:
Compared with healthy controls, children with ADHD showed significantly higher serum GABA levels and GABA/Glu ratios (both p < 0.001), whereas serum Glu levels did not differ significantly (p = 0.059). The GABA/Glu ratio demonstrated the best diagnostic performance, with an area under the curve of 0.87, sensitivity of 76.55%, and specificity of 85.83%. Serum GABA levels were positively correlated with both inattention and hyperactivity-impulsivity scores, while the GABA/Glu ratio showed the strongest correlations with both symptom dimensions (all p < 0.001). After 12 weeks of treatment, serum GABA levels and the GABA/Glu ratio decreased significantly, whereas serum Glu remained unchanged.
Conclusion:
The serum GABA/Glu ratio may serve as a promising biomarker for the auxiliary diagnosis, severity assessment, and treatment monitoring of ADHD. However, further independent validation is required before clinical application.
