ALTERED PAIN PROCESSING AND CORTICO–STRIATAL–THALAMIC CIRCUITRY IN CHILDREN WITH EARLY-ONSET PSYCHOSIS

: Pain and somatosensory aversions are understudied features of early-onset psychosis (EOP). We aimed to identify clinical and neurobehavioral correlates of abnormal pain and somatosensory experiences in children with EOP.
Methods: Clinical assessments and child- (male or female; ages 12-18 years)/parent-reported outcomes were administered to children with EOP (N=31) and compared to chronic pain (CP, N=29), attention-deficit/hyperactivity disorder (ADHD, N=30), and healthy controls (HCs, N=20). Children with EOP and HCs were additionally phenotyped using quantitative sensory testing (QST), cognitive tasks, and structural and functional magnetic resonance imaging (MRI). The EOP cohort also completed a questionnaire battery at 6-months follow-up.
Results: Children with EOP showed more severe pain and somatosensory aversions than those with ADHD or HCs, but less than CP patients, with reports stable at follow-up. Thermal sensitivities on QST were associated with negative symptom severity (ρ=0.49, p=0.009) and self-reported cognitive difficulties (ρ=-0.37, p=0.009). Using fMRI, EOP patients exhibited increased evoked pain responses in the striatum (p<0.05) (Figure 1A) and higher cortico-striatal-thalamic connectivity (p<0.001) (Figure 1B), while striatal connectivity patterns reflective of dopamine transporter density (Figure 1C), were linked to negative symptoms (ρ=-0.42, p=0.05) and pain-related parameters (ρ=0.65, p=0.001). Reduced striatal and paracentral volumes were observed (p<0.05), with nucleus accumbens volumes inversely associated with pain episode frequency (ρ=-0.49, p=0.02).
Conclusions: Pain and somatosensory disturbances in EOP are associated with disruptions in cortico–striatal–thalamic circuits. Upon further validation, clinical and neurobehavioral markers that can detect dysregulated pain behaviors in EOP may represent a novel approach for monitoring children with EOP.