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The biopsychosocial model is a widely accepted approach to chronic pain management and pain-related disability. The biopsychosocial model includes physical, cognitive, affective, and behavioral components. In general, the biological component includes a physical disturbance that leads to a painful stimulus. The psychosocial components of cognition, affect, and behavior can impact the multidimensional experience of pain by affecting perception of pain and adjustment to ongoing pain-related disability. Affective factors include emotions towards a subject, such as depression, pain-related anxiety, helplessness, and anger. Cognitive factors include thoughts and beliefs based on knowledge, such as catastrophizing, fear avoidance, decreased self-efficacy, hypervigilance, willingness to change, and acceptance.1,2 Behavioral includes actions towards subject and can be based on affective and cognitive factors.

Psychological factors can contribute to an existing diagnosed medical problem and/or can also be a part of an overall diagnostic criteria for psychiatric disorders. While it is well-established that common psychiatric disorders such as depression, anxiety, posttraumatic stress disorder (PTSD), psychotic disorders, and personality disorders influence the experience of pain, less is known about other psychiatric disorders. Under the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Text Revision (DSM-5-TR), individuals meeting diagnostic criteria s can be diagnosed with  disorders such as somatic symptom disorder, illness anxiety disorder, functional neurological symptom or conversion disorder, psychological factors affecting other medical conditions, factitious disorder, other and unspecified somatic symptom and related disorders, etc. 3 Furthermore, psychological factors involved in opioid-use related disorders can also contribute to physical disorders and perception of pain.


A variety of biopsychosocial factors can influence the perception of pain.4,5,6 Predisposing factors include genetics, neurobiology, physiology, psychology, mental health, cognitive functioning, cultural factors, and socioeconomic status.7,8 Precipitating factors include illness, traumatic or stressful events, abuse, substance use, medications, comorbid conditions and other stressors. Perpetuating factors can include chronic physiologic processes (e.g., disease) and primary and secondary gain.

Epidemiology including risk factors and primary prevention

The epidemiology of the wide array psychological factors that affect physical disorders is limited, largely due to broad manifestations, under diagnosis, and under documentation. In the US, approximately over 25% of people suffer from chronic pain.9 Research has shown depression significantly predicts onset of new chronic pain and vice versa.10,11 The prevalence estimates of major depression in chronic pain vary from 5% to 85%.12 In general, most systematic reviews on the relationship between pain and depression suggest that chronic pain precedes depression.8 In addition to depression, anxiety related to pain is an important factor  related to  ongoing pain.The prevalence of anxiety disorders in chronic pain is approximately 35%.13 The prevalence of other psychiatric conditions in co-occurrence with chronic pain include approximately 20% in PTSD and 9-58% in borderline personality disorder.14,15

Primary prevention includes surveillance and monitoring for psychological factors and illnesses consistently. This can be done by primary care providers administering the Patient Health Questionnaire-9 (PHQ-9) or General Anxiety Disorder-7 (GAD-7) regularly or at the onset of illness along with precipitating factors mentioned previously.


Psychoneuroimmunology suggests that activation of the proinflammatory cytokine network (both at the periphery and central nervous system) can lead to a constellation of symptoms, including alterations in pain sensitivity, such as exaggerated pain response (hyperalgesia), sleep disturbance, and fatigue. The activation of proinflammatory cytokines, possibly acting in concert with stress, might lead to an increased sensitization of the central nervous system, which serves as a possible neuronal substrate for amplification of normative bodily sensations5 and affects both serotonin and norepinephrine neurotransmitter systems that appear to exert effects via spinal pathways, subsequently playing a modulating role in pain, sleep, and fatigue5, 6,10

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Psychologic factors can lead to the development of psychiatric conditions which in turn can further exacerbate the experience of pain. Conversely, physical disorders can influence psychological factors. Because this can become a vicious cycle, it is important to understand the psychological factors affecting physical disorders and how to approach them. In the acute setting, the pain condition may lead to negative thoughts and subsequent maladaptive responses by the patient. Pain beliefs (pain-related fear, self-efficacy), anger, and passive coping can significantly affect pain response further. Chronic pain is defined as any pain lasting greater than three months.16 Chronic pain is related to longer durations of mood symptoms.17 Chronic pain patients with mental disorders tend to report higher levels of pain and be less active, contributing to greater disability and life interference.2

The common feature of these disorders is the chronicity, social dysfunction, occupational difficulty, increased health care use, and high level of dissatisfaction for both the clinician and patient.18 Clinical features can include feelings of depression, anxiety, anger, excessive thoughts or behaviors, preoccupation, altered voluntary motor or sensory function and are further discussed below when they meet the diagnostic criteria outlined in the DSM-5-TR.3

Specific secondary or associated conditions and complications

The differential diagnoses in individuals with chronic pain and mental disorders include the following:

  • Depression: patient suffers from lowering of mood, reduction of energy, and decrease in activity. Capacity for enjoyment, interest, and concentration is reduced, and marked tiredness after even minimum effort is common. Sleep is usually disturbed, and appetite is diminished. Self-esteem and self-confidence are almost always reduced and, even in mild form, some ideas of guilt and worthlessness are often present.6
  • Anxiety: dominant symptoms are variable but include complaints of persistent nervousness, trembling, muscular tension, sweating, lightheadedness, palpitations, dizziness, and epigastric discomfort.19
  • Illness anxiety disorder(formerly known as hypochondriasis): anxiety and preoccupied thoughts of having or acquiring a serious illness are present for a minimum of 6 months, with minimal or no somatic symptoms. If somatic symptoms are significant, the diagnosis of somatic symptom disorder would be more appropriate. 1,4
  • Posttraumatic stress: typical features include episodes of repeated reliving of trauma in intrusive memories (flashbacks), dreams or nightmares occurring against a persistent background of a sense of numbness and emotional blunting, detachment from other people, unresponsiveness to surroundings, anhedonia, and avoidance of activities and situations reminiscent of the trauma. There is usually a state of autonomic hyperarousal with hypervigilance, an enhanced startle reaction, and insomnia.19
  • Munchausen syndrome (also known as factitious disorder): patient feigns symptoms repeatedly for no obvious reason and may even inflict self-harm to produce symptoms or signs. Motivation is obscure and presumably internal with the aim of adopting the sick role. Disorder is often combined with marked disorders of personality and relationships.19
  • Malingering: DSM-5 does not consider this as a psychiatric disorder.4 Person also feigns illness (with obvious motivation and/or external incentives). This excludes Munchausen syndrome, in which self-harm is a feature.19
  • Somatic symptom disorder: key feature is the presence of prominent somatic symptoms with distressing thoughts, feelings, and behaviors about illness lasting more than 6 months.3
  • Adjustment disorder: key feature is the presence of maladaptive psychologic and behavioral symptoms resulting directly from the presence of a medical illness within 3 months of stressor.4
  • Functional Neurological Symptom Disorder (also known as conversion disorder): Key feature is the presence of one or more symptoms of altered voluntary motor or sensory function that is incompatible with recognized neurological or medical conditions and is not better explained by another medical or mental disorder. This condition generally causes significant distress or impairment in social or occupational areas.3
  • Psychological Factors Affecting Other Medical Conditions: An essential feature is the presence of one or more clinically significant psychological or behavior factors that adversely affect a medical condition and increase risk of morbidity or mortality. Psychological or behavioral factors include psychological distress, poor coping styles, denial of symptoms, or poor medical compliance.3

Essentials of Assessment


Evaluations are generally based on 3 sources of information: (1) observation and interview of the patient; (2) information from others (e.g., family, significant others, other clinicians) that corroborates, refutes, or elaborates on the patient’s report; and (3) medical records.20

The primary assessment tool is direct face-to-face interview of the patient. Evaluations based solely on review of records and interviews of persons close to the patient are inherently limited by a lack of the patient’s perspective. Furthermore, the clinical interview provides a sample of the patient’s interpersonal behavior and emotional processes and can either support or refute diagnostic inferences from the history.

General interviewing approaches and tips to keep in mind include

  • Establish an open and judgement free zone.
  • Begin with broad screening questions and then proceed with specific questions.
  • Approach sensitive topics in a nonthreatening manner.21
  • Balance open and close-ended questions.
  • Respond to emotion in a respectful and empathetic way.

The following information should be elicited22

  • History of present illness
  • Safety (suicidal or homicidal ideations, access to weapons)
  • Past medical history (significant medical problems or prior hospitalizations, history of head trauma, chronic pain conditions, psychiatric conditions and treatments received)
  • Current medications (including psychotropic use), psychiatric history (illnesses, treatment received, outcomes)
  • Family history (including psychiatric illnesses)
  • History of alcohol, smoking, and other substance use
  • Psychosocial history (legal history, trauma, current socioeconomic status, cultural factors)
  • Functional history (discussed later)
  • Review of systems (including psychiatric symptoms)20

Key information that should be derived from the interview should include the following:

  • Are symptoms minimized or exaggerated by the patient or others?
  • Does the patient appear to provide accurate information?
  • Do particular questions evoke hesitation or signs of discomfort?
  • Is the patient able to communicate about emotional issues?
  • How does the patient respond to the clinician’s comments and behaviors?20

Physical examination

The physical examination should be thorough because, even if there are no neurologic findings, a systemic illness may be present that is producing psychiatric symptoms. The physical exam should contribute towards identifying whether the underlying cause is

  • “Physical disorder mimicking mental disorders
  • Physical disorder caused by mental disorders or their treatment
  • Physical disorder accompanying mental disorders”23

Vital signs and a detailed musculoskeletal and neurologic examination, including a mental status exam, are of particular importance. Components of a mental status examination include appearance, behavior, speech, emotion, mood, affect, thought process and content, perception, cognition, insight, and judgment.4

On occasion, patients may exhibit physical signs that provide insight that a comprehensive psychological evaluation may be warranted. For instance, Waddell signs were developed in 1980 to identify patients with low back pain who were likely to experience poor surgical outcomes and can help to identify nonorganic aspects of pain.24 Having three or more out of five of the following signs constitutes a positive result

  • Tenderness tests: superficial and diffuse tenderness and/or nonanatomic tenderness
  • Simulation tests: movements which produce lumbar pain without actually causing that movement, such as axial loading and pain with simulated acetabular rotation
  • Distraction tests: positive tests are rechecked when the patient’s attention is distracted, such as a straight leg raise test
  • Regional disturbances: regional weakness or sensory changes which deviate from accepted neuroanatomy
  • Overreaction:  inappropriate, exaggerated, or disproportionate reaction to testing

Clinicians should interpret these signs with caution as organic components cannot be excluded, and results should not be used for medico-legal purposes.24

Close involvement in the patient’s general medical evaluation and ongoing care can also improve the patient’s care by promoting cooperation, facilitating follow-up, and permitting prompt reexamination of symptomatic areas when symptoms change.20

Functional assessment

Psychological factors may acutely or chronically affect function and should be monitored for improvement or decline. Structured assessment of physical, cognitive, and instrumental daily function may be useful in assessing areas of concern and disease severity. Functional assessments include assessment of previous and current activities of daily living (e.g., bathing, dressing) and instrumental activities of daily living (e.g., driving, taking medication as prescribed, shopping).20 Standardized assessments such as 6 Minute Walk Test, Mini Mental Evaluation, Barthel Index, among others can help evaluate and quantify physical, cognitive, and daily function, respectively. These assessments are further discussed in detail elsewhere.

Assessments regarding quality of life and community re-integration are also crucial to evaluate the impact of psychosocial factors on patients’ lives and are further discussed below.

The Pain Disability Questionnaire was developed as a measure of functional status of patients with pain and is based on the biopsychosocial approach to pain.7,25,26 Similarly, the Oswestry Low Back Disability Questionnaire by the American Academy of Orthopedic Surgeons asks patients to rate how their back pain affects everyday activities related to functional and psychosocial status.27 There are ten questions each with ratings from 0 (meaning no impact) up to 5 (meaning complete impact). Scores are then combined to identify disability level and are shown below:

Total ScoreDisability Level

Laboratory studies

There are no specific guidelines about which tests should be routinely done. Several studies have demonstrated the limited utility and higher cost of ambulatory screening. Patients on psychotropic medications should be monitored for side effects specific to that therapy. When substance use is suspected, determining blood alcohol levels or screening for substances of abuse may be especially important.20,28 Examples of tools available for screening for substance abuse/use include the Opioid Risk Tool (ORT), Screener and Opioid Assessment for Patients with Pain (SOAPP), and the CAGE.29 Lastly, appropriate laboratory studies should be ordered based on the differential of physical disorders mimicking mental disorders or physical disorders accompanying mental disorders.


Specialized modalities (e.g., computerized scanning, magnetic resonance imaging) can be used to screen for neurologic conditions with behavioral manifestations that could be mistaken for a psychiatric disorder (e.g., frontal lobe brain tumor, CNS infection, or neurodegenerative diseases).4

Several neuroimaging studies suggest that specific neural networks modulate aspects of emotional behavior and are implicated in the pathophysiology of mood disorders: medial prefrontal cortex and closely related areas in the medial and caudolateral orbital cortex, amygdala, hippocampus, and ventromedial parts of the basal ganglia.30

Supplemental assessment tools

The current methodology and content of psychiatric diagnosis, growing specificity of treatment planning in regard to both medication and psychosocial interventions, and nature of the health care delivery system all influence the context that determines the use of clinical rating scales and neuropsychologic tests to inform assessment and treatment planning.31

Examples of functional domains to be measured and corresponding clinical rating scales include the following:

  • Quality of life (e.g., Quality of Life Enjoyment and Satisfaction Questionnaire)
  • Mental health status and functioning (e.g., Clinical Global Impression Scale, Global Assessment of Functioning Scale, Social and Occupational Functioning Assessment Scale)
  • Cognitive disorders (Delirium Rating Scale Revised-98, Mini-Mental State Examination)
  • Alcohol use disorder (CAGE Questionnaire)
  • Mood disorders (Beck Depression Inventory Second Edition, Hamilton Depression Rating Scale, Patient Health Questionnaire, Geriatric Depression Scale)
  • Anxiety disorder (Hamilton Anxiety Rating Scale)20

Neuropsychologic testing has a broad range of applications, but the decision to order neuropsychologic testing for an individual patient remains a matter of clinical judgment. Neuropsychologic testing may be requested when cognitive deficits are suspected or there is a need to grade for severity or progression of deficits over time and for distinguishing between cognitive disorders (e.g., dementia), malingering, or factitious disorders.20

Early predictions of outcomes

Age (younger age at pain onset), sex (women > men), number of pain areas, frequency and severity of pain, psychosocial issues (problems with social and leisure activities), unemployment, and compensation are mediating factors in the course and prognosis of individuals with chronic pain and mental disorders.4,10,2,32

Waddell signs do not discriminate organic from non-organic sources of pain, and do not correlate with psychological distress. However, positive results have been associated with poorer treatment outcomes, and higher pain levels.33


According to the International Classification of Functioning, Disability and Health, environmental factors that can influence the functioning of individuals with mood disorder and chronic widespread pain include the following: location, climate, building design, immediate family/friends, health professionals, individual attitudes of family/friends/health professionals, access to institutions, and availability of social security services/systems (i.e., aimed at providing income support).34

Social role and social support system

An assessment of family, peer networks, cultural identity, and other support systems plays an important part in the psychiatric evaluation because of the potential role of these systems in ameliorating or augmenting the patient’s signs and symptoms of illness. This is particularly true when evaluating individuals with complex biopsychosocial challenges or serious psychiatric or general medical conditions.20

Professional issues

Throughout the assessment, useful clinical information is obtained by being sensitive to issues of development, culture, and the clinician’s own possible biases or prejudices about patient’s subculture, race, ethnicity, primary language, health literacy, disabilities, sex, sexual orientation, familial/genetic patterns, religious and spiritual beliefs, and social class influencing the patient’s symptoms and behavior.20

Rehabilitation Management and Treatments

See Part 2.

Cutting Edge/Emerging and Unique Concepts and Practice

See Part 2.

Gaps in the Evidence-Based Knowledge

See Part 2.


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Original Version of the Topic:

Armando S. Miciano, MD. Psychological factors affecting physical disorders Part 1: Evaluation and differential diagnosis. 9/20/2014

Previous Revision(s) of the Topic

Kareen A. Velez, MD. Psychological factors affecting physical disorders Part 1: Evaluation and differential diagnosis. 12/15/2020

Author Disclosure

Shaima Khandaker, MD
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Darryl Chow, MD
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Melissa Mafiah, MD
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