American Health & Medical Research Association
Pain, fatigue & chronic conditions

Why symptoms persist, and what the best explanations can’t yet do

The models doctors use to explain lasting pain and other symptoms, how functional neurological disorder is diagnosed, and what the largest treatment trials did and didn't show.

By the Health Research USA editorial team

Published Last updated October 2026

Written from the sources listed below; links checked October 2026. It touches on medicines, doses or health conditions and has not yet been reviewed by a licensed clinician, so use it to prepare for a conversation with yours. How we research and review

Sources26, listed below Reading time15 minutes
On this page
  1. Three Models Doctors Use to Explain Lasting Symptoms
  2. Mood, Childhood Adversity and a Two-Way Street
  3. Functional Neurological Disorder: Diagnosed by What the Exam Shows
  4. How Often a Functional Diagnosis Turns Out to Be Wrong
  5. What the Largest Treatment Trials Found
  6. Somatic Symptom Disorder and a Changing Vocabulary
  7. What a Positive-Signs Diagnosis Should Include
  8. The Takeaway

Her left leg began to drag on a Tuesday. By the weekend she could barely walk, and MRI scans of her brain and spine were normal. The neurologist did not stop at the images. The examination turned up Hoover’s sign, a bedside test for functional leg weakness that the National Institute of Neurological Disorders and Stroke (NINDS) lists among the positive signs of functional neurological disorder (FND).

Many people hear that diagnosis as the doctors found nothing. It means close to the opposite. FND is diagnosed by what the examination shows, and its symptoms are genuine. Even under its older label, conversion symptoms, studies since 1970 found that only about 4% of people given the diagnosis later turned out to have a different disease that explained their symptoms.

FND is the sharpest test of a wider question: why do some symptoms persist after tests stop explaining them? Medicine has useful models for that. What it lacks, as the largest treatment trials show, is a reliable way to turn those models into better outcomes.

Three models doctors use to explain lasting symptoms

The biopsychosocial model (1977)

In a 1977 Science essay, G. L. Engel argued that the dominant biomedical model of disease left no room for the social, psychological and behavioral sides of illness. He proposed a biopsychosocial model in its place, as a guide for research, teaching and everyday care. Its breadth is its strength and its limit: it tells clinicians where to look, not what will help a particular person.

The fear-avoidance model (2000)

The fear-avoidance model explains how a sensible reaction to pain can help keep it going. First proposed in 1983 and reviewed in 2000 in the journal Pain by Johan W. S. Vlaeyen and Steven J. Linton, it puts fear of pain at the center. People who confront that fear tend to become less afraid over time. People who avoid feared movements can stay afraid or grow more so.

The review links that fear to escape and avoidance, constant watchfulness for signs of illness, muscle tension, and disuse: lost fitness and guarded movement. Vlaeyen and Linton concluded that pain-related fear and avoidance appear essential to the development of a chronic problem for a substantial number of people with musculoskeletal pain. Not for everyone, and not as the only factor.

A related idea, pain catastrophizing, was defined in a 2009 Johns Hopkins review as a negative thinking and emotional response to pain, expected or present. The label has become a problem of its own. In an international survey of 3,521 patients and caregivers published in 2022, most of them in the US, 12% said a clinician had called them a pain catastrophizer and reported feeling blamed, judged and dismissed; respondents also tied the term to negative gender stereotypes. A pattern of fear can be worth working on; a label that makes people feel accused is a poor start.

Persistent physical symptoms (2024)

The newest umbrella comes from a 2024 seminar in The Lancet led by Bernd Löwe of University Medical Centre Hamburg-Eppendorf. It applies the term persistent physical symptoms to bodily complaints that cause distress and go on for months, whatever is behind them. They can follow an infection, an injury, a medical disease or a stressful event, or begin with no clear trigger. As they persist, the authors note, their link to any clearly identifiable disease process often weakens.

Its list of contributors refuses to pick a side:

Biological Psychological and social
Persistent inflammation Adverse experiences early in life
Epigenetic profiles (chemical marks that change how genes are used) Depression and anxiety about illness
Disturbances in the immune system, metabolism and gut microbes Unhelpful expectations about symptoms, focusing on them, learned symptom patterns and avoidance

Many of these, the authors write, are shared across symptoms and diagnoses. The basic care they describe addresses any underlying disease process and pairs it with validation, appropriate reassurance and an explanation spanning body, mind and circumstance, adding targeted psychological or drug treatment when needed. One proposed biological route for pain, a nervous system grown oversensitive, is weighed in our article on central sensitization.

Mood, childhood adversity and a two-way street

Depression and pain travel together, and the traffic runs both ways. In a 2011 study of 500 primary care patients with persistent back, hip or knee pain, Kurt Kroenke and colleagues at Indiana University noted that the two co-occur 30% to 50% of the time. Over 12 months, a change in pain predicted later depression severity, and a change in depression predicted later pain, with similar strength.

Childhood adversity raises the odds of adult pain without deciding anyone’s fate. A 2023 meta-analysis in the European Journal of Psychotraumatology drew on observational studies covering 826,452 adults. People exposed to direct adverse childhood experiences, such as abuse or neglect, had 45% higher odds of reporting chronic pain as adults. The odds climbed with the count: about 29% higher with one adverse experience and nearly double with four or more. These are population associations, not forecasts for any individual, and they cannot prove cause.

Functional neurological disorder: diagnosed by what the exam shows

NINDS, in a page reviewed in March 2026, describes FND as a problem with how brain networks function rather than with the brain’s structure. The symptoms can involve any part of the body, are genuine, and are not produced on purpose. Brain scans and other neurological tests are often normal, and no single test or biomarker confirms it.

Selma Aybek and David L. Perez summed it up in a 2022 clinical review in The BMJ: “Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments.” Neurologists look for positive signs, such as Hoover’s sign for leg weakness, or entrainment, a test in which the person moves an unaffected limb at a set rhythm while the clinician watches a tremor. Across 22 studies of motor symptoms and 27 of seizure-type symptoms, Aybek and Perez report specificities of 64% to 100% for such signs, meaning that at the high end the signs seldom appear in people without FND.

A 2018 review in JAMA Neurology notes that DSM-5, the American Psychiatric Association’s diagnostic manual, replaced psychogenic with functional and dropped psychological stress as a requirement for the diagnosis. A 2022 review in The Lancet Neurology, led by Mark Hallett of NINDS, groups four variants that share causes and mechanisms: functional seizures, functional movement disorders, a chronic dizziness condition, and functional cognitive disorder, a relative of the memory complaints our brain fog article examines.

The Hallett review also corrects a common assumption: “Psychological stressors are common risk factors for functional neurological disorder, but are often absent.” NINDS agrees that stress and childhood adversity are risk factors in adults but are not present in everyone with FND. The disorder is more common in women and affects children as well as adults. NINDS says movement symptoms usually begin around the late 30s and functional seizures in the late 20s, often alongside depression, anxiety or post-traumatic stress disorder.

How often a functional diagnosis turns out to be wrong

The fear that a functional diagnosis hides a missed disease has history behind it. In a 2005 systematic review in The BMJ, Jon Stone and colleagues at the University of Edinburgh pooled 27 studies of 1,466 people diagnosed with conversion symptoms, the older term, followed for a median of five years. In studies from the 1950s, 29% turned out to have a disease that explained their symptoms. The figure fell to 17% in the 1960s and to 4% in each decade from the 1970s through the 1990s. The authors judged the drop most likely due to better-designed studies rather than the arrival of brain CT scans. Those studies followed people whose symptoms had been judged unexplained by disease, so the figure shows how often that older, exclusion-based diagnosis held up, not how accurate today’s positive-signs approach is.

Four percent is low, not zero, and mistakes cluster. A 2021 systematic review in the Journal of Neurology suggests multiple sclerosis (MS) is among the most common sources of confusion with FND, in both directions, and notes that the two can occur together. Among the errors it described: leaning too hard on a person’s psychiatric conditions when diagnosing FND, and on imaging when diagnosing MS. NINDS likewise notes that FND can coexist with other disorders.

A functional diagnosis is usually right, then, but not a permanent guarantee; a new or different symptom deserves its own examination.

What the largest treatment trials found

NINDS names physical therapy and psychotherapy as the two main approaches to FND. Two large trials funded by the UK’s National Institute for Health and Care Research tested one of each, and both are easy to misread in either direction.

CODES (2020). Published in The Lancet Psychiatry, this trial randomly assigned 368 adults with dissociative seizures, another name for functional seizures, in England, Scotland and Wales to cognitive behavioral therapy (CBT) plus standardized medical care or to standardized care alone. On its main measure, monthly seizure frequency at 12 months, the difference was not statistically significant: a median of 4 seizures with CBT against 7 without. The CBT group did better on many secondary measures, including how bothersome seizures were, seizure-free stretches, quality of life and daily functioning. Seizure severity and depression and anxiety scores did not differ, and the p values were not corrected for the many comparisons made. Adverse events were similar in both groups.

Physio4FMD (2024). Published in The Lancet Neurology, this trial randomly assigned 355 adults with functional motor disorder at 11 hospitals in England and Scotland to nine sessions of specialist physiotherapy plus follow-up, or to usual care: referral to community neurological physiotherapy, an active treatment rather than nothing. Pandemic disruptions removed 89 people from the main analysis, which included 241. On physical functioning at 12 months, the specialist group scored 3.5 points higher out of 100, a gap within the range of chance in a trial built to detect 9 points. More people in the specialist group rated their motor symptoms improved and reported better mental health, and the full 2025 report found several secondary outcomes favoring specialist physiotherapy and none favoring usual care. Its authors flag two weaknesses: the usual-care group waited longer to start, and most outcomes were self-reported.

A follow-up analysis of the specialist arm found that a stronger sense of control over recovery predicted improvement, while older age and a belief that symptoms were permanent predicted less. Illness duration, pain and fatigue, often assumed to signal a poor outlook, did not predict results, and the authors described the predictors they did find as weak.

Smaller trials pull in different directions:

  • An online program. A JAMA Neurology trial from Melbourne, published online on October 26, 2026, randomized 107 adults with functional seizures confirmed by video EEG. Adding a five-session self-guided internet program to standard care cut the monthly seizure rate to roughly a third of standard care’s, an effect still present at 12 months. Oddly, the therapist-guided version did not significantly reduce seizures, and the two versions did not differ significantly from each other.
  • Brief psychodynamic therapy. A 2026 Brazilian pilot of 91 adults reported large gains from 12 weekly sessions, but the comparison group received no matched attention, and the authors call for confirmatory trials.
  • A relaxation add-on. A 2026 Indian pilot gave 50 people with functional seizures structured education about the condition plus either a guided practice called yoga nidra or a sham version. Median monthly seizures fell from 6 or 7 to 0.5 in both groups, so the added practice deserves none of the credit: a warning about before-and-after success stories.

In the library’s evidence terms, the claim that CBT or specialist physiotherapy improves how people with FND feel and function is positive evidence with a contested interpretation: real gains on many measures, mostly self-reported, but not on the main outcome either large trial chose. The claim that either reliably reduces seizures or restores physical function is not supported by those trials, and newer approaches are too thinly tested to judge. NINDS adds that people with functional seizures should not take anti-seizure medicines, which may worsen symptoms; whether an existing prescription should change is a question for the treating neurologist. Therapy details belong to the library’s coming entries on physical therapy and psychological strategies.

Somatic symptom disorder and a changing vocabulary

Psychiatry’s diagnosis for persistent, distressing symptoms changed sharply in 2013. Under DSM-5, somatic symptom disorder (SSD) requires one or more distressing or disabling bodily symptoms lasting more than six months, plus thoughts, worry or time spent on them that is out of proportion. It no longer requires ruling out a medical disease. A 2021 scoping review led by Löwe, two of whose authors worked on the manual’s text revision, stresses that SSD can be diagnosed alongside any physical illness, a deliberate break from treating medically unexplained as if it meant psychological.

The American Psychiatric Association’s patient page, reviewed in July 2024 by Philip R. Muskin, M.D., M.A., makes the same points for the public. The symptoms may or may not come with a diagnosed medical condition, nobody receives the diagnosis just because a medical cause cannot be found, and people with it are not faking. What decides it is how excessive the thoughts, feelings and behaviors around the symptoms are.

The diagnosis has critics. In a 2013 BMJ commentary, Allen Frances warned that the new criteria risked mislabeling many people as mentally ill, and Löwe’s review grants that this worry cannot be fully dismissed. Self-report surveys put SSD at about 13% of the general population, but no population study has used standard diagnostic interviews, and the reviewers expect self-report to overestimate it. Roughly a quarter of patients with various physical diseases meet the criteria, including 18.5% in one study of people with heart failure. How to measure excessive also remains unsettled.

The vocabulary keeps moving for a reason. Older manuals described affected patients as difficult. A 2013 paper explaining the DSM-5 change says SSD deliberately plays down medically unexplained symptoms as the defining feature, and ICD-11, in effect internationally since January 2022, uses a counterpart called bodily distress disorder. The newer words name what a person lives with, not what tests failed to find.

What a positive-signs diagnosis should include

A functional diagnosis made well should leave you with more than a label. Drawing on the evidence above, a thorough one tends to include:

  1. Named signs. Which positive signs did the examination find, and can the clinician show or explain them? The diagnosis rests on what was found, not on what was missing.
  2. Alternatives weighed. Which other conditions were considered, and what ruled them out? This matters most where errors cluster, as with MS.
  3. Anything else going on. Is another condition present alongside the functional one? FND can coexist with other disorders, and SSD can sit alongside any physical disease.
  4. A mechanism, not a dismissal. An account of how brain networks are misfiring, never a version of there’s nothing wrong.
  5. A plan with names attached. Which therapy or rehabilitation is proposed, who provides it, and what the trials say it can and cannot be expected to do.
  6. A reason to look again. Which new or changed symptoms would reopen the question.

Finding that care is the business of our forthcoming guide to persistent unexplained symptoms.

When to get help right away

New neurological symptoms need an examination before anyone calls them functional, and some cannot wait for an appointment. Stroke signs on the Centers for Disease Control and Prevention’s list include sudden numbness or weakness of the face, an arm or a leg, mainly on one side; sudden confusion or difficulty speaking; sudden trouble seeing or walking; and a sudden severe headache with no known cause. CDC’s instruction is to call 911 right away. An earlier functional diagnosis does not change that. And if persistent symptoms have brought on hopelessness or thoughts of suicide or self-harm, the 988 Suicide & Crisis Lifeline answers calls and texts at 988, free and confidential, at any hour.

The Takeaway

The models of persistence earn their place. They tell clinicians where to look, show how protecting yourself from pain can become a trap, and name contributors from inflammation to expectation without pretending one explains everyone. FND shows the progress: it is now diagnosed on positive signs, and even the older, exclusion-based diagnosis was overturned only about 4% of the time in studies since 1970.

The trials show what is unfinished: the two largest missed their main targets while improving how people felt and functioned, and the newest positive results are small. If you are given a functional diagnosis, the most useful thing to ask for is the evidence behind it: the signs found, the alternatives ruled out, and an honest account of what treatment can be expected to do.

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