The High-Risk Model of Threat Perception Modulates Learning of Placebo and Nocebo Effects and Functional Somatic Disorders.

Threat activation or deactivation in the brain-body is associated with learned nocebo or placebo somatic effects induced by fake invasive medical-surgical procedures. Some functional somatic disorders (FSDs) originate as acute nocebo somatic effects and can become 30-50% of chronic somatic presentations to primary care physicians. Patients with FSD overutilize medical-surgical services, despite the lack of identified pathophysiology, and are at risk for morbidity from unintentional iatrogenic injury. The Conditioned Response Model (CRM) of learning postulates three innate mechanisms, modulated by trait hypnotizability, which drive placebo and nocebo somatic effects and FSD. The High Risk Model of Threat Perception (HRMTP) postulates 10 psychosocial risk factors that modulate threat perception, driving placebo and nocebosomatic effectsandbiologically embedded FSD. Psychosocial factors and the trait of high and low hypnotizability modulate threat and are postulated to reduceheart rate variability(HRV), inducing autonomic nervous system(ANS)dysregulation. Reduced HRV was found in a large (N = 6,891) sample of patients with FSD. A total of 50% of patients with FSD with chronic pain (n = 224) without identified pathophysiology had a Paradoxical Increase in hand Temperature (PTI) during experimental threat induction. The HRMTP predicts that PTI associated with ANS dysregulation is associated with the risk factor Adverse Childhood Experiences (ACEs). This ACE prediction was independently confirmed. Learning predicts that threat activation by unconscious neutral stimuli (CS) can amplify nocebo and FSD and can negate placebo effects in clinician-patient relationships. Identifying psychosocial risk factors that modulate threat perception enables the diagnosis of FSD by inclusion and not simply by excluding pathophysiology.