Similar or Different? Comparing Point Prevalence of Functional Somatic Syndromes Across Age With Generalized Additive Models

Functional Somatic Syndromes (FSSs) are characterized by clusters of symptoms that are not medically explained. The most well-known FSSs are Chronic Fatigue Syndrome (CFS), which is characterized by fatigue and exertion (1), Fibromyalgia (FM), which is characterized by musculoskeletal pain (2), and Irritable Bowel Syndrome (IBS), which is characterized by bowel complaints (3). As FSSs exist in the absence of detectable pathology they are often perceived as less serious than other well-defined medical diseases. However, the functional limitations and impairment in Quality of Life and work participation that patients with FSSs experience are similar to the impairments and limitations patients with well-defined medical diseases experience (4). 
So far, the etiology of FSSs remains unclear. It is assumed that FSSs may arise from a complex interaction between biological and psychosocial factors (5). 
Research that has been conducted has found striking resemblance between FSSs. In general, FSSs have a striking comorbidity (6): individuals with an FSSs are more likely to develop another FSS compared to controls (7). While CFS appears to be more distinct from FM and IBS, FM and IBS predict each other (8). These findings can be explained by the great clinical and diagnostic overlap of symptoms between FSSs (9). Although FSSs share several diagnostic criteria, there are differences in how long symptoms need to be present to diagnose a FSS: while for CFS and IBS symptoms need to be present for six months, for FM symptoms need to be present for three months only. 
Beyond that, while the majority of the predictors for FSSs development is syndrome-specific, one fourth is shared by at least two of the three FSSs (8). Potential risk factors for developing an FSS are female sex, anxiety, depression, young, but also old age (10,11). While a few studies suggest that high SES predicts FSS development, the vast majority argues that low SES predicts FSS development (12–15)
Traditionally, FSSs are seen as distinct syndromes which is a common approach in the field of medicine. However, the abovementioned findings question such an approach. The discussion whether FSSs are one syndrome entity with different syndrome-types rather than distinct syndromes (16,17) is longstanding and also known as the Lumper-Splitter discussion (16). While the Lumpers consider FSSs as one syndrome entity with different phenotypes, the Splitters consider FSSs as distinct syndromes. 
So far, there is no conclusive evidence which solves the Lumper-Splitter discussion. It is possible that the mixed findings are caused by limitations within previous studies. 
One of the main issues concerns the assessment whether an individual has an FSSs. Previous studies relied on self-report mostly. However, research has found that 69% of IBS, 90% of CFS and 77% of FM diagnoses are missed with self-report (18). Beyond that, many individuals, which do not meet the diagnostic criteria, are included when using self-report of FSSs. In addition to it, some studies excluded individuals with comorbid FSSs, although comorbidity is common (7). Therefore, both points question whether previous population samples actually represent individuals with FSSs. 
When researching FSSs through cohort study datasets, a researcher might be forced to use several cohort study datasets as many datasets include one FSS at best. This has the consequence that researchers might be hesitant to compare FSSs as it might limit the quality of comparison. In addition to this issue, within analyses and interpretation, previous research did not take into account that the diagnostic criteria of symptom chronicity differ between FSSs. All the before mentioned limitations can produce artificial differences between FSSs through which FSSs might appear to be more distinct than they actually are.
So far, research aiming to solve the Lumper-Splitter discussion focused on comorbidities and risk factors of FSSs mostly. A new and promising approach could be to compare the point prevalence of FSSs across age. Similarities in the prevalence of FSSs across age would be in favor of the Lumpers, while differences would be in favor of the Splitters. 
Therefore the aim of this study is to use Generalized Additive Models to model the prevalence of FSSs, namely CFS, FM and IBS, across age and to compare the modelled curves.
In addition, the study will investigate whether alignment of symptom chronicity would impact the findings as the trajectories might become more similar. Lastly, the study will assess the interaction of age with sex and age with SES to re-validate previous findings.
By assessing the prevalence of FSSs across age, we could illuminate the relationship between FSSs and etiological mechanisms of FSSs. Ultimately, this study investigates whether FSSs are one syndrome entity or distinct syndromes.