Objective Up to 10% of the general population experiences persistent somatic symptoms (PSS). Numerous studies in a variety of health domains are dedicated to identifying factors that are associated with PSS onset. The present study aimed to provide an overview of predictors for PSS onset in the general population and the related health domains. Methods A systematic search was performed identifying longitudinal cohort studies that examined factors associated with PSS onset in the general population. Included studies measured potential predictors before PSS onset and were categorized according to the dynamic biopsychosocial model. Four levels of evidence were discerned for predictors, based on the number of studies and percentage of consistent findings. Results In the 154 articles eligible for analysis, 27 PSS subtypes were studied, with primary focus on fibromyalgia (25.0%) and irritable bowel syndrome (23.3%). Of the >250 predictors of PSS onset, 46 were investigated more than once and showed consistent results. Strong evidence identifies biological (e.g., infections, body weight-related metrics), psychological (e.g., sleep problems, psychopathology), interpersonal (life events, childhood/interpersonal stress), contextual (employment), and health behavioral (health care utilization) predictors. Conclusions The results provide strong evidence for factors from all dynamic biopsychosocial domains, although interpersonal and health behavioral factors are relatively under investigated. Thus, evidence suggests that reduction of predictors of PSS onset to a specific factor/domain may be too restrictive. There is no evidence that this differs per PSS subtype. Exploring all domains and measuring common factors across subtypes are essential to improve the clinical course of PSS.

Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of nocebo effects on pressure pain at baseline (N = 69) and 1-month follow-up (N = 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions on the pain-increasing function of a sham transcutaneous electrical nerve stimulation device, then decreased via extinction. One month later, the same procedures were repeated to explore their stability. Results suggest that nocebo effects were induced in the healthy control group during baseline and follow-up. In the patient group, nocebo effects were only induced during follow-up, without clear group differences. Extinction was only observed during baseline in the healthy control group. Further comparisons of nocebo effects and extinction indicated no significant changes across sessions, possibly suggesting their overall magnitudes were stable over time and across groups. In conclusion, contrary to our expectations, patients with fibromyalgia did not have stronger nocebo hyperalgesia; instead, they might be less responsive to nocebo manipulations than healthy controls. Perspective: The current study is the first to investigate group differences in experimentally manipulated nocebo hyperalgesia between chronic pain and healthy populations at baseline and 1-month follow-up. Since nocebo effects are common in clinical settings, their investigation in different populations is essential to explain and minimize their adverse effects during treatment.

Objective Persistent somatic symptoms (PSSs) are defined as symptoms not fully explained by well-established pathophysiological mechanisms and are prevalent in up to 10% of patients in primary care. The present study aimed to explore methods to identify patients with a recognisable risk of having PSS in routine primary care data. Design A cross-sectional study to explore four identification methods that each cover part of the broad spectrum of PSS was performed. Cases were selected based on (1) PSS-related syndrome codes, (2) PSS-related symptom codes, (3) PSS-related terminology and (4) Four-Dimensional Symptom Questionnaire scores and all methods combined. Setting Coded electronic health record data were extracted from 76 general practices in the Netherlands. Participants Patients who were registered for at least 1 year during 2014-2018, were included (n=169 138). Outcome measures Identification methods were explored based on (1) PSS sample sizes and demographics, (2) presence of chronic conditions and (3) healthcare utilisation (HCU) variables. Overlap between methods and practice specific differences were examined. Results The percentage of cases identified varied between 0.3% and 7.0% across the methods. Over 58.1% of cases had chronic physical condition(s) and over 33.8% had chronic mental condition(s). HCU was generally higher for cases selected by any method compared with the total cohort. HCU was higher for method B compared with the other methods. In 26.7% of cases, cases were selected by multiple methods. Overlap between methods was low. Conclusions Different methods yielded different patient samples which were general practice specific. Therefore, for the most comprehensive data-based selection of PSS cases, a combination of methods A, C and D would be recommended. Advanced (data-driven) methods are needed to create a more sensitive algorithm for identifying the full spectrum of PSS. For clinical purposes, method B could possibly support screening of patients who are currently missed in daily practice.