Brain–gut axis mechanism of subthreshold nonsuicidal self-injury addictive features in adolescents

Abstract Nonsuicidal self-injury (NSSI) is associated with an increased risk of suicide. As the diagnostic criteria outlined in DSM-5 and other related clinical studies, a patient must have engaged in self-injurious behavior at least 5 times within the past year. However, patients with fewer than 5 self-injury behaviors should not be ignored. Our study included 46 adolescents aged 10–19 years with subthreshold NSSI (sNSSI), along with a control group of 50 healthy adolescents matched for age and other factors. We collected resting-state functional magnetic resonance imaging data and stool samples. The Ottawa Self-Injury Inventory and Deliberate Self-Harm Inventory were used to evaluate self-harm behaviors and addictive features. Local brain activity was assessed using fractional amplitude of low-frequency fluctuations (fALFF), and brain regions with abnormal fALFF were selected as seeds for whole-brain functional connectivity analysis. Stool samples were identified using 16S rDNA amplicon sequencing, and the LDA Effect Size method was used to explore significant differences between grouped samples. Mediation analysis was performed to investigate the brain–gut axis mechanisms of addictive features in sNSSI. We found that compared with healthy controls, sNSSI patients have abnormal fALFF in left thalamus and posterior cingulate cortex, dysconnectivities of left thalamus, and decreased Prevotellaceae. Our results suggested that addictive features of sNSSI may have a brain–gut mechanism. Furtherly, patients with 1–4 NSSI behaviors in the past year should have separate name for identification, such as “subthreshold NSSI”.