Cleveland Clinic meeting March 2011

Somatoform Disorders

Objectives • Review the definition of Somatoform Disorder • Discuss the meaning and utility of ‘medically unexplained symptoms’ as it relates to Somatoform Disorders • Review the CBT, epigenetic, psychneuroimmune, and cytokine models • Outline some treatment options

Comparison of Somatoform Disorders: ICD-10 vs. DSM-IV ICD-10 Somatoform Disorders (F45)

DSM-IV Somatoform Disorders (300)

Somatization disorder

Somatization disorder

Undifferentiated somatoform disorder

Undifferentiated somatoform disorder

Hypochondriacal disorders (includes Body dysmorphic disorder)

Hypochondriasis Body dysmorphic disorder

Somatoform autonomic dysfunction Persistent somatoform pain disorder

Pain disorder

Other somatoform disorders Somatoform disorder, unspecified

Somatoform disorder, not otherwise specified

Somatoform Disorders (DSM-IV) • Common feature: Presence of physical symptoms that suggest a medical condition but not fully explained by the medical condition, direct effects of a substance, or another mental disorder. • Symptoms must cause clinically impairment or distress in social, occupational, or other areas of functioning. • Physical symptoms are NOT intentional (i.e. voluntary) • Outside cultural norms • How a somatoform patient perceives their health is directly related to their distress, disability and utilization of hearth care services. They tend to rate themselves as more impaired physically, psychologically, work, socially, sexually and overall health compared to panic disorder patients.

Somitization: ICD-10 “…repeated presentation of physical symptoms with persistent requests for medical investigations, in spite of repeated negative findings and reassurances by doctors that the symptoms have no physical basis” (World Health Organization. The ICD-10 classification of mental and behaviors disorders. Clinical description and diagnostic guidelines. Geneva: WHO. 1992)

Table 3: Prevalence figures for a sample of functional somatic syndromes Functional Somatic Syndrome

Estimated population prevalence

Chronic fatigue syndrome

0.007 – 0.56% (Ranjith 2005)

Irritable bowel syndrome

3 – 20% (Brandt, Bjorkman et al. 2002)

Fibromyalgia

0.5 – 5% (Neumann and Buskila 2003)

Non cardiac chest pain

25% (Fass and Dickman 2006)

Chronic pelvic pain

15% women (Zondervan and Barlow 2000)

Tension-type headache

38% (Jensen and Stovner 2008)

Incidence of Somatoform (Functional) Disorders in Chronic Pain Population • • • • •

Examples: IBS, CFS, Fibromyalgia, IC 16%-53% (Dworkin &Caligor,1988) 33% (Katon et al ,1985, Reich et al, 1983) 100% (Oewn-Salters et al, 1996) vs non-Somatoform Pain Disorder: - greater number outpatient visits - more frequent hospitalizations - higher overall health care expenditures - 10-20% US medical budget spent on patients with somatoform disorders

Key Features Medically Unexplained Symptoms (MUS): ‘physical symptoms that prompt the sufferer to seek healthcare but remain unexplained after an appropriate evaluation’ (p. 139) Commonalities More in females Adverse early experience Sudden onset (often associate with injury or infection) Multiple symptoms in the same patient with no order of onset Waxing/waning of symptoms Heightened stress response (adrenocortical, sympathetic) Recalcitrant to treatment (Buffington CAT. Developmental influences on medically unexplained symptoms. Psychotherapy and Psychosomatics, 2009, 78, 139-144)

Philosophical Underpinnings The term ‘medically unexplained (or functional) symptoms (MUS)’ refers to ‘physical symptoms that prompt the sufferer to seek healthcare but remain unexplained after an appropriate medical evaluation’ (Richardson RD, Engel CC "Evaluation and management of medically unexplained physical symptoms." Neurologist 2004 Jan;10(1):18-30)

• The most unwavering criterion is whether or not the ‘objective’ data obtained by the clinician sufficiently accounts for the patients symptoms. • At the time neurologist Dr. Weir Mitchell wrote “Injuries of Nerves and Their Consequences” (1872), phantom limb and causalgia were considered MUS • Classical Newtonian Physics: Materialism: all that exists is physical; the universe is governed by a set of natural laws- linearity/proportionality Reductionism: complex system is nothing but the sum of its parts, and that an account of it can be reduced to accounts of individual constituents; implies causality- the whole is equal to the sum of its parts

Relevant Questions • First what defines ‘medically’? This brings us back again to the issues of materialism and reductionism. Do genetic vulnerability and altered nociceptive processing constitute ‘medical explanations’? • Second, what defines an ‘appropriate work-up’? Some rely on a physical exam, others an interview, still others imaging studies; all of which have been shown to be flawed when it comes to ‘explaining’ pain. • Third, broad discrepancies in the background, diagnostic sophistication, and training of physicians. No doubt you can show the results of an exanimation and tests to three different clinicians and get three different interpretations • Fourth, is the assumption that the degree of specificity and sensitivity of our existing medical technology is sufficient to detect all related physical abnormalities. The last 15 years or so have seen a remarkable revolution and evolution in our understanding of pain with the advent of functional brain imaging technology. Who knows what will be reveled with continued probing at the genetic level. • Perhaps we should re-name these symptoms as those ‘beyond the comprehension and sophistication of current medical science’ (BCSCMS) and place the burden of proof where it belongs.

Proposed Changes in DSM-V: Somatic Symptoms Disorders • Elimination of ‘medically unexplained’ symptoms as a diagnostic criterion • Somatisation • Hypocondriasis • Pain Disorder

Complex Somatic Symptom Disorder

• If depressive disorder exists; code both

• Goals: (a) Eliminate any implicit reference to mind-body dualism (b) Recognize shared common features of somatic symptoms and cognitive distortions (Dimsdale & Creed J Psychosomatic Res, 2009, 66 (6), 473-476)

Somatic Symptoms Disorders: DSM-V • Psychological interpretation of bodily symptoms (especially pain) is frequently inappropriate or unjustified (Merskey H. Pain 2009, 145, 4-5)

• Diagnosed using positive cognitive and behavioral features: • Somatic symptoms are: severe, intense and bothersome multiple or single specific (localized) or nonspecific chronic (> 6 mos) may be normal bodily sensations (i.e. dizziness) poor health-related QoL

• Cognitive: misattributions excessive concern or preoccupation with symptoms and illness high levels of health-related anxiety

• Behavior: increased pattern of healthcare utilization unresponsive to therapies new treatments exacerbate symptoms or lead to new side effects/complications (Dimsdale J, Creed F. The Journal of Psychosomatic Research, 2009, 66, 473-476)

Explanatory models of MUS (van Ravenzwaaij et al Mental Health in Family Medicine 2010;7:223–31)

• • • • • • • • • •

Somatosensory amplification theory Sensitisation theory Sensitivity theory Immune system sensitisation theory Endocrine dysregulation theory Signal filter theory Illness behaviour theory Autonomic nervous system dysfunction theory Abnormal proprioception theory Cognitive behavioural therapy model

Expanded CBT model of hypothesized autopoietic cycle of symptom maintenance (V. Deary et al. Clinical Psychology Review ,2007, 27 (7), 781-797)

‘Pain’ Stimulating/Enhancing Factors • • • • • • •

Anticipation/expectation Uncertainty ’Imagined allodynia’ Hallucinated pain ‘Pain catastrophizing’ Mood states ‘Limbically augmented pain syndrome or LAPS’ • Conditioning and learning • ‘Conditioned nociception’ • Epigenetic

Neurovisceral Integration Model JF Thayer, JF Brosschot. Psychneuroendocriniology November 2005, Pages 1050-1058

Summary • The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. • Using a neurovisceral integration model: autonomic imbalance and decreased parasympathetic tone are the final common pathway linking negative affective states and conditions to ill health. • The central nervous system (CNS) network that regulates autonomic balance (central autonomic network, CAN) is closely related and partially overlaps with networks serving executive, social, affective, attentional, and motivated behavior • A common reciprocal inhibitory cortico-subcortical neural circuit serves to regulate defensive behavior, including autonomic, emotional and cognitive features. • This inhibitory cortico-subcortical circuit is linked to psychological processes with health-related physiology. • When the prefrontal cortex is taken ‘offline’ parasympathetic inhibitory action is withdrawn and a relative sympathetic dominance associated with disinhibited defensive circuits is released, which can be pathogenic when sustained for long periods. • This state is indicated by low heart rate variability (HRV), which is a marker for low parasympathetic activation and prefrontal hypoactivity. • HRV is associated with a range of psychological and somatic pathological conditions, including immune dysfunction.

Neurovisceral Integration Model: Complexity Theory • • • • •

Dynamic relationship Patterns of organized variability Operates ‘far-from-equilibrium’ Lability and flexibility Rigid regularity (associated with mortality, morbidity, illness, pre-mature death)

Epigenetic Modulation of Gene Expression “Converging lines of (EMGEX) research suggest that when a pregnant female is exposed to a sufficiently harsh stressor, the hormonal products of the ensuing stress response may cross the placenta and affect the course of fetal development, resulting in durable changes in brain, autonomic, endocrine and immune function. While of potential survival value, these changes also appear to increase vulnerability to life stressors, putting these individuals at greater risk of developing disorders characterized by pain and discomfort in some environments.” ( p 140)

Buffinton CA. Developmental Influences on Medically Unexplained Symptoms. Psychother Psychosom, 2009;78:139–144

Somatization: A psychoneuroimmune perspective Robert Dantzer. Psychoneuroendocrinology, 2005,30 (10), 947-952

• Summary • Proinflammatory cytokines produced by cells of the innate immune system in response to pathogen-associated molecular patterns and to endogenous danger signals act on the central nervous system via afferent and humoral pathways • These peripheral cytokines trigger a brain cytokine system that organizes the sickness response in its subjective, behavioral, and metabolic components. • Prolonged activation of this system can precipitate the development of depressive disorders in vulnerable patients. • The mechanisms that are responsible for the transition from sickness to depression may involve alterations in tryptophan metabolism. • The brain cytokine system can become sensitized in response to non-immune stressors or to immune stressors occurring early in life.

Somatization: A Psychoneuroimmune Persepctive ‘…somatization may be nothing else then the outward manifestation of sensitization of the brain cytokine system that is normally activated in response to activation of the innate immune system and mediates the subjective, behavioral and physiological components of Dantzer R. Psychoneuroendocrinology, 2005,30, 947-952 sickness.’ (p. 948)

‘This figure shows that peripheral inflammation may induce a central neuroinflammation with increased levels of proinflammatory cytokines, which together may cause ‘psychosomatic’ and depressive symptoms and, consequently, clinical syndromes, for example, chronic fatigue syndrome (CFS), depression and somatiform disorder’. ( p 77)

Maes M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Current Opinion in Psychiatry 2008, 22:75–83

Cytokines: Associations potentially relevant to Fibromyalgia • • • • • • • •

IL-1b: hyperalgesia, fatigue, fever, sleep, substance P antinocicpetion (increase GABA, decrease NMDA); NE and E stimulate its releases TNF-alpha: stress; regulates substance P expression, REM sleep, allodynia; increase EAA; NE and E stimulated its release IL-1Ra: stress; inhibits IL-8 expression IFN-gamma: stress; anxiety, lower substance P; myalgias IL-2: Myalgias; cognitive dysfunction; IL-6: Stress, fatigue, hyperalgesia, depression; NE, E, substance P stimulate its release; activates the sympathetic nervous system IL-8: substance P stimulates its production; mediates sympathetic pain IL-10 Blocks pain (Wallace et al. Rheuma, 2001, 40, 743-49 )

Cytokine-induced sickness behavior Keith W. Kelley KW et al, Brain, Behavior, and Immunity 17 (2003) S112–S118

Community Physicians’ Strategies for Patients Medically Unexplained Symptoms Anderson M et al, Clinical Research and Methods, 2007, 40 (2), 111-118

Treatment • Basic medical examination and tests • Pharmacological therapy: AEDs, Antidepressants, NSAIDs, atypical antipsychotics, opioids, sedative/hypnotics

• Modality therapy/P.T.: heat, ice, NMT • Functional restoration: graded exercise, pool • Psychological/behavioral: reassurance (control expectations/goals), relaxation/biofeedback/hypnosis, CBT

• “Be a doctor”: reassurance, acceptance, regular followup

• Interventional therapy: ‘by indication not by exclusion’

Community Physicians’ Strategies for Patients With Medically Unexplained Symptoms Anderson M et al, Clinical Research and Methods, 2007, 40 (2), 111-118

Disease of pain • This summer (2011) an expert panel convened by the Institute of Medicine is to report on the efforts to understand ‘…chronic pain and highlight the need for an all-encompassing approach that treats it as a disease of both brain and body.’ (Time, 3-1-11, p 66)

Balansreaktioner vid hot

Copyright © Tomas Waldegren

Pain and Stress SUPERSYSTEM Facilitory vs excitatory nociceptive transmission Nervous

Systemic circulation

Systemic circulation

diffusion autonomic

autonomic Peptides Hormones Neurotransmitters Endocannabinoids Cytokines

circulation

arousal vs recovery

migration

Endocrine

Immune Systemic circulation

Chapman, Tuckett, Song. The J Pain, 2008, 9 (2), 122-45

pro-inflammation vs anti-inflammation

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