Altered pain processing and associated neural circuitry disruptions in adolescents with early-onset psychosis
Schizophr Res. 2026 Oct 7;298:34-43. doi: 10.1016/j.schres.2026.09.039. Online ahead of print.
ABSTRACT
BACKGROUND: Abnormal pain processing and somatosensory aversions are underappreciated clinical features of early onset psychosis (EOP). We aimed to identify their clinical, neurobehavioral, and brain circuit level correlates.
METHODS: Clinical assessments and child (ages 12-18 years) and parent-reported outcomes were administered to adolescents with EOP (N = 31) and compared to chronic pain (CP, N = 27), attention-deficit/hyperactivity disorder (ADHD, N = 30), and healthy control (HCs, N = 20) cohorts. Adolescents 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 baseline and 6 months.
RESULTS: Adolescents with EOP showed more severe pain and somatosensory aversions than those with ADHD or HCs, but less than CP patients; these reports remained stable at follow-up. Among patients with EOP, thermal sensitivities on QST were associated with negative symptom severity and self-reported cognitive difficulties. Functional MRI revealed increased pain-evoked responses in the striatum and elevated cortico-striatal-thalamic connectivity in EOP relative to HCs. Striatal connectivity patterns, spatially corresponding to dopamine transporter density, were linked to negative symptoms and pain-related parameters. Structurally, individuals with EOP showed reduced striatal and paracentral volumes. More reduced nucleus accumbens volume associated with greater frequency of pain episodes.
CONCLUSIONS: This study shows a preliminarily association between disruptions in cortico-striatal-thalamic circuitry, pain processing, and somatosensory disturbances in EOP. Upon further longitudinal validation in a larger cohort, markers of altered pain processing may provide a clinically accessible index of neurobiological disturbances underlying psychopathology in EOP.
PMID:42843043 | DOI:10.1016/j.schres.2026.09.039