Schizophrenia research · 2026
Altered pain processing and associated neural circuitry disruptions in adolescents with early-onset psychosis.
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van der Heijden Hanne, Cao Amanda, van Gool Raquel, Yekedüz Merve Koç, Vrolix Lise, Barrett Talia, Randall Edin T, Golden Maya, Goldman Maria, Lu Benjamin, Chang Joyce C, Glahn David C, Fogler Jason M, Sethna Navil, Gonzalez-Heydrich Joseph, Upadhyay Jaymin
Аннотация
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.
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.