From Healing Deities to Healthcare Difficulties: The Struggle to Understand Functional Somatic Disorders

Written By Lucia Holbrook-Brown

Lucia Holbrook-Brown

Illustrations by Ansen Chamberlain

In the second century CE, the Greek philosopher Aelius Aristides arrived in Rome, motivated by his early career success [1]. However, Aristides’ ambitions were stalled when he fell ill and became consumed by his health [2]. Aristides suffered debilitating symptoms, including chronically severe abdominal pain and persistent fatigue [1]. His writings reveal disproportionate anxiety related to his health, which exacerbated his disabilities [1, 2]. Aristides turned to Asclepius, the preeminent healing god, seeking comfort, guidance, and healing through ritual and devotion [2]. Though Aristides experienced occasional remissions, his illness never truly resolved, and he died decades later, still in pursuit of a cure [2]. Aristides’s story, though ancient, is not unfamiliar to our age. Today, similar chronic diseases continue to burden not only individuals and their families but also clinicians and healthcare systems. Disorders like the one Aristides suffered from  — now referred to as functional somatic disorders (FSDs) — account for 30% of primary care visits and $174 billion annually. Despite the millennia between Aristides and ourselves, many are trapped in cycles of persistent pain, left only with costly medical consultations, heightened health anxiety, and limited effective treatments [3].

The Quintessential Question: What are Functional Somatic Disorders?  

FSDs refer to a group of disorders characterized by chronic, distressing body symptoms — such as pain, fatigue, and gastrointestinal issues — that are not fully accounted for by identifiable medical conditions [4, 5]. These physical symptoms, called somatic symptoms, significantly disrupt daily life despite an absence of observable disease [6]. The leading theoretical model contends that somatic symptoms arise from psychological factors [7, 8]. While fleeting somatic symptoms are common, such as experiencing butterflies before public speaking, FSDs are diagnosed when physical symptoms are chronic, impairing, and disproportionate to any identifiable medical cause [9, 10]. The classification of FSDs remains highly contested [11]. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) categorizes FSDs under Somatic Symptoms and Related Disorders, focusing on the disproportionate psychological distress associated with somatic complaints, regardless of whether a medical cause exists [12, 13]. Similarly, the International Classification of Diseases (ICD-11) outlines bodily distress syndrome, which is characterized by excessive concern with bodily symptoms, often but not exclusively due to an unattributable cause [14, 15]. Notably, the ICD-11 framework also includes chronic widespread pain (CWP), which explicitly requires the exclusion of an identifiable medical cause [14]. CWP recognizes psychological factors, but it does not rely on labeling an individual’s concern as excessive [16]. Both the ICD and DSM overemphasize psychological aspects of disease and fail to provide classifications that integrate mind and body [17].  

The limited understanding of FSDs’ underlying mechanisms has resulted in uncertainty surrounding their classification [11]. The diagnostic approach relies on ruling out abnormal biological processes that may explain unusual somatic symptoms, rather than directly looking for markers that identify FSD [4, 17]. As a result, some experts do not view classification of FSDs into individual syndromes as a current priority because they believe the underlying biological mechanisms must be discovered before classification can accurately proceed [7]. However, other experts believe that regardless of the unknown mechanism, FSDs should be classified with chronic illnesses [7]. To address the controversy in classification, the term functional somatic disorder was proposed in anticipation of the 2022 revision of the ICD [17]. Though the term functional somatic disorder is not universally accepted, it emphasizes an integrated approach of the mind and body that is missing from past definitions [17]. 

FSDs encompass a range of conditions — such as functional neurological disorder (FND), irritable bowel syndrome (IBS), and fibromyalgia — that share a common feature: persistent, distressing physical symptoms that lack an identifiable biomedical cause [18, 19, 20, 21]. FND presents with altered sensory or motor function — including impaired movement, chronic dizziness, brain fog, and non-epileptic seizures — but is only diagnosed in the absence of a detectable neurological condition [19, 22, 23]. Non-epileptic seizures, for instance, may resemble epileptic convulsions — presenting with full-body convulsions, twitching limbs, lapses in awareness, and muscle weakness or paralysis — but occur without measurable abnormal brain electrical activity [24, 25, 26, 27]. Management of FND symptoms is expensive and often futile, as seen with non-epileptic seizures, which do not respond to anti-seizure medications [22, 28, 29]. IBS involves chronic abdominal pain and disordered bowel habits [30]. IBS is widespread, affecting an estimated 12% of the global population; however, treatment is largely ineffective, leaving almost one billion people with unmanaged symptoms [20, 30]. Fibromyalgia is a chronic musculoskeletal pain disorder characterized by widespread muscle aches, fatigue, and sleep disturbances [21, 31]. The intense pain and fatigue associated with fibromyalgia can significantly decrease a person's quality of life, which has been hypothesized to increase suicide risk [31, 32, 33]. Despite conflicting views in classification, the categorization of specific FSDs into disorders such as IBS remains useful for treating symptoms restricted to one organ or body system [17]. 

Mystery Mechanisms: Biological and Psychological Origins

In order to find a clearer basis for diagnosing and defining FSD, a multifaceted approach is required, which integrates medical and psychological perspectives in pursuit of identifying biomarkers: biological indicators of disease [6, 19, 34]. Biomarkers measure results of biological processes, such as proteins or genes, that reflect physiological processes [35]. Improved clinician understanding of disorders can be facilitated with biomarkers, as they can aid diagnostic accuracy, treatment, and disease trajectory [34, 36, 37]. Dysfunction within and between the immune system and the brain is being explored as a potential contributor to FSD and could thus contribute to diagnostic criteria [17, 38, 39, 40]. In FSDs, the immune system is activated by systemic low-grade inflammation (SLI), a state in which tissues express inflammation without resulting in structural or functional change [41, 42]. SLI is caused by cytokines, small proteins produced by immune cells that relay messages between cells to promote cell functions responsible for bodily inflammation and may contribute to the somatic symptoms seen in FSDs [41, 42]. Two specific cytokines are biomarkers of SLI in FSD: IL-6 and hs-CRP [42]. IL-6 induces the expression of hs-CRP, which mediates inflammation. IL-6 and hs-CRP are important indicators of inflammation and are considered potential biomarkers for FSD that could help uncover the mechanism. SLI associated with FSDs is characterized by elevated IL-6 and hs-CRP levels in the blood, a marker that is often unique to FSDs [42]. High levels of IL-6 and hsCRP are also associated with the promotion of inflammation, increasing physical symptom intensity and frequency, and leading to heightened pain sensitivity [43]. However, IL-6 and hsCRP are not officially recognized as diagnostic tools in clinical practice [42]. Understanding the role of the immune system in FSD allows scientists to develop more precise diagnostics and targeted therapies, leading to better outcomes for people with FSD [36]. Therapies might target the immune pathways involved, should they be elucidated [36]. 

Abnormalities in the brain are being investigated in an attempt to uncover the cause of FSDs, with the existing research focusing primarily on functional neurological disorder [44, 45, 46]. Neuroimaging has uncovered differences in brain structure and function in individuals with FND compared to individuals without FND [28]. Individuals who reported severe impairment in daily functioning due to FND displayed reduced volume of their insular cortex, a brain region that influences one’s sense of self-awareness, emotional processing, and interoception [28, 47]. Interoception refers to the awareness of the internal bodily signals, such as the sensation of pain [48]. When interoception is altered, individuals may experience increased pain, leading to more intense symptoms [28, 49, 50]. Functional imaging is an additional tool in the characterization of FND, as it can provide evidence of activity changes in specific areas of the brain [28]. In individuals with FND, there can be decreased activity in areas associated with movement, such as the supplementary motor area (SMA), and increased activity in areas in the insular cortex [28, 51]. Additionally, those with FND have increased neuronal activity between parts of the limbic system, a part of the brain that regulates emotions, and the motor circuit [28]. The increased activity potentially indicates that there is heightened limbic influence over motor behavior [28]. Promoted limbic and insular activity may shed light on how psychological symptoms lead to the manifestation of seizures and other somatic symptoms in FND [28, 51, 52]. Although brain activity changes have only been concretely studied in FND, similar mechanisms may be at play in other FSDs, warranting further research [53]. 

In addition to the immune system and brain involvement in symptom development, FSDs are influenced by an individual's psychological health [54]. FND, fibromyalgia, and IBS often occur simultaneously with other diseases, referred to as comorbidities [54]. Anxiety and depression are common comorbidities, impacting about one-third of those with IBS and half of those with either fibromyalgia or FND [55, 56, 57, 58]. In fibromyalgia and IBS, comorbid mental disorders can exacerbate somatic symptoms [59, 60]. However, the presence of a comorbid disorder with FND does not necessarily exacerbate neurological symptoms such as non-epileptic seizures [58]. Understanding the complex interactions between psychological comorbidities and FSDs is essential for refining diagnosis and treatment to improve outcomes for those affected [23, 61]. 

Trials and Triumphs in Treatment 

Treatment for FSDs requires a multifaceted approach, involving psychiatrists, general practitioners, and medical specialists [62]. A large focus of treatment for FSDs is improving psychological health through the use of psychotherapies, such as cognitive behavioral therapy (CBT) and psychodynamic therapy (PDT) [63]. CBT posits that thoughts and beliefs can promote and maintain mental disorders, and therapy aims to unlearn these [64]. In the context of FND, CBT aims to reduce symptoms by increasing one’s bodily awareness, challenging symptom-related anxieties, and changing illness-promoting behaviors [65]. PDT is based on practices that focus on the individual’s internal world and aims to deconstruct misperceptions and misinterpretations of external realities by making the unconscious conscious [66]. PDT for FND aims to link symptoms to an individual’s emotional experiences and thus regulate somatic symptoms by regulating emotions [65]. Non-pharmaceutical therapies such as CBT show promise for treating fibromyalgia, but their precise effects on symptom management are still being investigated [67, 68]. Furthermore, a lack of long-term research on CBT’s ability to manage IBS symptoms presents uncertainty around the use of psychotherapy as a treatment option [62]. While CBT and PDT have been able to relieve some symptoms, they do not cure people with FSD [65].

Psychiatric pharmaceutical intervention can supplement psychological therapies in the treatment of FSDs [36]. Often, people with FSDs are prescribed antidepressants like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake Inhibitors (SNRIs), which increase the levels of the chemical messengers serotonin and norepinephrine in the brain [36, 69]. Increased levels of serotonin and norepinephrine can help stabilize mood and potentially limit psychological triggers to somatic symptoms [70]. Tricyclic antidepressants work similarly to SNRIs by targeting both serotonin and norepinephrine. However, unlike SNRIs, tricyclic antidepressants target a broader range of neurotransmitters, often leading to more severe side effects [37, 71]. When prescribed for FSDs, tricyclic antidepressants are often slightly more effective, but have more severe side effects [37, 71]. Despite the common use of SSRIs, SNRIs, and tricyclic antidepressants in the treatment of FSDs, their efficacy varies [72, 73]. Antipsychotics are other pharmaceutical interventions used to treat FDSs that regulate dopamine, a neurotransmitter involved in reward processing and motivation, and serotonin [72, 74]. However, antipsychotics have shown limited success in the treatment of FSDs [72, 75, 76]. Psychiatric pharmaceutical interventions often fail, leading to increased frustration among doctors and people with FSDs [36]. Fibromyalgia, IBS, and FND are chronic conditions, and as a result, psychological health interventions alone are often not enough, and additional treatments are required [63].

Another area of focus for the treatment of FSDs is improving physical health [36]. A common first-line treatment for FSDs is physical therapy [36]. Individuals with FSD often experience physical disability, leading to a more sedentary lifestyle that contributes to poorer physical health and intensifies existing symptoms [77]. Physical therapy that is especially focused on mobility and strength building can reduce the pain associated with fibromyalgia and IBS, as well as the risk of developing comorbid disorders [77, 78]. While physical therapy has not been studied in the management of FND, its success in treating fibromyalgia and IBS suggests that it could be beneficial in treating FND [79]. Another common treatment for FSDs is neurostimulation, which uses electrical stimulation to modulate irregular brain activity [80]. Neurostimulation has varying degrees of invasiveness and works by stimulating underactive areas, suppressing overactive areas, and disrupting abnormal activity in the brain [81, 82, 80]. Certain neurostimulation is believed to reduce inflammation throughout the body, which may help alleviate the pain symptoms associated with FSDs [83]. With exceptional promise in treating IBS, neurostimulation has demonstrated both a reduction in abdominal pain and regulation of bowel movements [84]. Although treatments are progressing, there has yet to be a broadly successful treatment for FSDs [36].

Past Plights, Present Pains, and Promising Prospects 

From Aristides’s time to today, chronic unexplained physical symptoms have imposed a burden on individuals and their healthcare systems. FSDs, especially FND, IBS, and fibromyalgia, remain challenging to classify, diagnose, and treat due to the absence of identifiable biomarkers, contested diagnostic criteria, and uncertain origins [4, 11, 19]. Although progress has been made in the recognition of FSDs as complex psychological and physiological disorders, a definitive understanding of FSDs remains elusive [8]. Emerging research on inflammatory biomarkers, neuroimaging findings, and psychological involvement offers promising directions to guide the field but has yet to yield a conclusive understanding of FSD mechanisms [28, 42, 54]. While current FSD treatment, including psychotherapy, medication, physical therapy, and neurostimulation, can offer symptom relief, there is no cure [36, 65]. Ultimately, the path forward lies in uncovering the underlying causes of FSDs, investing in multidisciplinary research, and developing evidence-based treatment strategies.

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Lucia Holbrook-Brown
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