L-Cystine is associated with the dysconnectivity of the default-mode network and salience network in attention-deficit/hyperactivity disorder. (March 2021)

• Record Type: Journal Article
• Authors: Wang, Liang-Jen; Lin, Liang-Chun; Lee, Sheng-Yu; Wu, Chih-Ching; Chou, Wen-Jiun; Hsu, Chia-Fen; Tseng, Huai-Hsuan; Lin, Wei-Che
• Is Part Of: Psychoneuroendocrinology. Volume 125(2021)
• Publication Date: 2021-03
• Subjects: ADHD -- Antioxidant -- Brain image -- Default-mode network -- Metabolite -- Salience; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2020.105105
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Distributed dysconnectivity within both the default-mode network (DMN) and the salience network (SN) has been observed in ADHD. L -cystine may serve as a neuroprotective molecule and signaling pathway, as well as a biomarker of ADHD. The purpose of this study was to explore whether differential brain network connectivity is associated with peripheral L -cystine levels in ADHD patients. We recruited a total of 31 drug-naïve patients with ADHD (mean age: 10.4 years) and 29 healthy controls (mean age: 10.3 years) that underwent resting state functional magnetic resonance imaging scans. Functional connectomes were generated for each subject, and we examined the cross-sectional group difference in functional connectivity (FC) within and between DMN and SN. L -cystine plasma levels were determined using high-performance chemical isotope labeling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Compared to the control group, the ADHD group showed decreased FC of dorsal DMN (p = 0.031), as well as decreased FC of precuneus-post SN (p = 0.006) and ventral DMN-post SN (p = 0.001). The plasma L -cystine levels of the ADHD group were significantly higher than in the control group (p = 0.002). Furthermore, L -cystine levels were negatively correlated with FC of precuneus-post SN (r = −0.404, p = 0.045) and ventral DMN-post SN (r = −0.540, p = 0.007). The findings suggest that decreased synergies of DMN and SN may serve as neurobiomarkers for ADHD, while L -cystine may be involved in the pathophysiology of network dysconnectivity. Future studies on the molecular mechanism of the cystine-glutamate system in brain network connectivity are warranted. Highlights: Peripheral L -cystine levels and the default-mode network (DMN) and salience network (SN) in ADHD was investigated. The ADHD patients showed decreased functional connectivity (FC) of dorsal DMN, precuneus-post SN and ventral DMN-post SN. In ADHD patients, L -cystine plasma levels were negatively correlated with FC of precuneus-post SN and ventral DMN-post SN. L -cystine may be involved in network dysconnectivity, and is linked to ADHD pathophysiology.