Neurobiological Underpinnings of Pain-Related Symptoms in Early Onset Psychosis

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ABSTRACT Patients with early onset psychosis (EOP) demonstrate poorer long-term prognosis and higher rates of residual symptoms and disability relative to cases of adult-onset psychosis. Children with EOP often report moderate to severe pain, which is not explained by discoverable causes or associated with objective findings (e.g., inflammation, swelling, or redness). Pain reported by EOP patients introduces significant functional impairment for the child and hinders basic activities such as self-care. While abnormal pain perception and processing in adults with psychosis has been documented, the clinical, behavioral, and neurobiological characteristics associated with pain in EOP have rarely been studied. A characterization of pain in EOP patients will provide a developmental window into earlier stages of this phenomenon and course of the illness as well as during a period of active CNS maturation. The objective of this proposal is two-fold. Objective 1 is to evaluate male and female EOP patients (N=30, 13-18 years of age) with clinical instruments informing on pain severity and quality, somatization, central sensitization and mental health. A parallel set of clinical questionnaires will be administered in age-gender matched healthy controls (HCs, N=30) and two matched clinical comparator conditions; complex regional pain syndrome (CRPS, N=30) and attention-deficit/hyperactivity disorder (ADHD, N=30). Objective 2 is to identify behavioral and neural correlates of dysregulated pain perception and processing in EOP patients (N=30) and HCs (N=30). For Objective 2, we propose to phenotype participants by combining the Structured Clinical Interview for DSM-5 (SCID-V) Axis I diagnoses, with additional modules from the Kiddie Schedule for Affective Disorders and Schizophrenia (KSAD), Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS), alongside assessment of pain sensitivity (quantitative sensory testing), cognition, and CNS function and structure using magnetic resonance imaging (MRI) based methods. We will also explore the utility of functional near infrared spectroscopy (fNIRS) in EOP. fNIRS is a non-invasive, cost-effective, and mobile neuroimaging method that has not been widely used in EOP. Our overarching hypothesis is that EOP patients presenting with severe psychiatric symptoms will present with a robust pain phenotype, while the function of central nervous system (CNS) structures implicated in top-down regulation of pain and sensorimotor processing are aberrant. To test our hypothesis, we propose the following Specific Aims. Aim 1: Characterize the presentation of pain in children with EOP. Aim 2: Define behavioral and neural correlates of dysregulated pain perception and processing in EOP. Exploratory Aim 3: Define resting-state CNS functional properties in EOP using fNIRS. To study dysregulated pain perception and processing in patients with EOP, our Boston Children’s Hospital based team will leverage our clinical and research expertise in pediatric pain and psychiatry, pain neurobiology, neuroimaging, biostatistics, among other domains.