Table 1.

Outcome measures.

Instrument	Information
Physical symptoms: Physical Symptom Questionnaire (PSQ-51)	Additional to the mean score, the following dimensions were discerned: CD/FND symptoms; postural orthostatic tachycardia syndrome (POTS); digestive symptoms; pain; fatigue; sleep score and sexual symptoms. (Allen et al., 2020; Van Hemert et al., 2004)
Pain: Brief Pain Inventory (BPI)	Average severity of pain in the last week was assessed. An average score of 3 or more on the BPI in the last week is the cut score for clinically significant pain.
General functioning: RAND 36-Items	The ​RAND 36-Item Health Survey ​taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. The higher the score, the better the functioning. These RAND 36 items are identical to the MOS SF-36.(Ware and Sherbourne, 1992) They were adapted from longer instruments completed by patients participating in the Medical Outcomes Study (MOS), (Tarlov et al., 1989) an observational study of variations in physician practice styles and patient outcomes in different systems of health care delivery, for HIV patients (Hays and Shapiro, 1992) and patients with chronic medical conditions (Stewart et al., 1989) and depressive disorders. (Wells et al., 1989)
Quality of life: EuroQol EQ-5D-5L	EQ-5D-5L percentages of patients scoring on the subscales mobility, selfcare, activities, pain and depression or anxiety were established. NICE does not recommend using UK EQ-5D-5L norm scores as there are issues with the scoring system, (NICE, 2020) hence we compared the mean score for the general health item with similar scores from other countries.
Childhood trauma: Adverse Childhood Experiences scale (WHO-ACE-IQ)	The WHO-ACE-IQ (WHO, 2018) provides a total score and differentiates between 9 domains: problems with marriage or parenthood, such as arranged marriage and unwanted pregnancies; parental neglect, parental illness, witnessing domestic abuse, being a victim of domestic abuse, being a victim of sexual abuse, experiencing bullying, external violence, and war experiences, all during childhood.
Current life events: Holmes and Rahe Life Events Stress Scale	The Holmes and Rahe Life Events Stress Scale assesses for 54 life events that can cause stress as they require a role transition that could be positive or negative in nature, whether they occurred over the last 12 months. A total score (Life Change Units) is provided based upon validated scores per life event (LCU).(Holmes and Rahe, 1967)
Chronic medical conditions	CBS checklist. Assesses presence and number of chronic medical conditions.(CBS, 2005)
Anxiety: GAD7	General Anxiety Disorder questionnaire (GAD-7) (Löwe et al., 2008) GAD-7 scores of 5 or higher indicate mild anxiety symptoms; scores of 10 or higher indicate a probability for an anxiety disorder.(Kroenke et al., 2010)
Depression: PHQ9	Patient Health Questionnaire-9 (PHQ-9) (Kroenke et al., 2001) PHQ-9 scores of 5 or higher indicate mild depressive symptoms; scores of 10 indicate a probability for a depressive disorder. (Kroenke et al., 2010)
Clinimetric measures:	Height, Weight, BMI, Waist circumference and Blood pressure recorded during first interview and Body Mass Index (BMI) calculated.
Inflammation markers: Cytokines TNFα; IL1β; IL6; IFNɣ; VEGF-a; ANG2 hSCRP	Tumor Necrosis Factor alpha (TNFα), (Baumeister et al., 2016; Zelová et al., 2013) Interleukin 1 beta (IL1β), (Kovacs et al., 2016a, Kovacs et al., 2016b) Interleukin 6 (IL6), (Money et al., 2016; Tanaka et al., 2014) Interferon gamma (IFNɣ), (Flaishon et al., 2000) Vascular endothelial growth factor A (VEGF-a) (Kut et al., 2007) and Angiopoietin-2 (ANG2) (Nataraj et al., 1999; Bai et al., 2014) hsCRP. (Seo et al., 2012) Before blood samples were taken, it was ascertained that the patient did not feel unwell, have an infectious condition, or needed anti-inflammatory medication in the week before the samples were taken.
Inflammation-associated microRNAs:	Targeted assessment of circulating (cell-free) inflammation-associated microRNAs miR-146a, miR-155, miR-21, miR-223, and miR-132.(Tahamtan et al., 2018) miR-146a and miR-155 are linked to inflammation and miR-21, miR-132, (Hewitson et al., 2019) miR-155 (Yee et al., 2017) are all linked to angiogenesis and vascular inflammatory responses
Chronic accumulative stress: Hair cortisol levels	Cortisol hair test was used as biomarker for chronic accumulative stress.(Staufenbiel et al., 2013) Hair samples were chosen as levels of the hormone in the blood and saliva can rapidly fluctuate, giving a poor picture of long-term concentrations.