A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques

Nonsuicidal self-injury (NSSI) demonstrates escalating prevalence among adolescents as a maladaptive behavior characterized by deliberate self-harm, yet its neurobiological underpinnings remain elusive. Spontaneous self-injurious behavior (SIB) in nonhuman primates (NHPs) emerges as a clinically relevant animal model for investigating NSSI pathogenesis and therapeutic interventions. However, previous studies have yet to comprehensively evaluate the translational value of self-injury in NHPs through integrated behavioral and neuroimaging characterization. In this study, we identified spontaneously self-injurious macaques within our NHP colony and performed multimodal assessments encompassing ethological profiling, neuroendocrine assays, metabolomic analysis, and neuroimaging. Our results revealed that SIB macaques exhibited biological patterns and temporal onset sequences of self-harm, accompanied by a locomotor and social interaction decrease based on 3-dimensional deep-learning recognition, sensory processing deficits, and impairments in emotional and cognitive processing. Biochemical profiling demonstrated reduced plasma concentrations of cortisol, serotonin, and oxytocin, coupled with metabolomic disturbances including up-regulation of digestive-related pathways and down-regulation of dopaminergic synaptic signaling and phosphatidylinositol metabolism. Neuroimaging analyses identified structural abnormalities featuring volumetric enlargement in amygdala and midbrain regions alongside gray matter reduction in the frontal and parietal lobes. Enhanced structural and functional connectivity was observed. Network-based statistics highlighted increased functional connectivity primarily between the frontal and parietal lobes. These alterations demonstrated a partial correlation with observed behavioral deficits in the self-injury macaques. Notably, a series of administration of low-dose ketamine had no effect on SIB and the physical index. Our integrative multi-omic approach elucidates the neurobiological phenotype of spontaneous SIB in macaques, highlighting the value of the SIB model for pathogenetic investigation and therapeutic development in human NSSIs.