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From Luke’s Journal Nov 2024 | Vol.29 No.3 | Mental Health II

Introduction

In a seminal paper, Naviaux¹ noted the significant rise in chronic illness over the past 70 years, which, despite advances in medical technology, presents significant ongoing challenges to the medical community. Naviaux observed that, compared to acute illness, chronic illness is characterised by recurrent, multi-system abnormality and failure in completing the healing cycle of intervention, treatment response and recovery.  Heterogeneity in illness trajectories, symptom presentation and biological markers are the norm.  This creates layers of complexity for researchers and practitioners in understanding and defining illness aetiologies and developing treatment pathways. Whilst specialisation has facilitated advances in the knowledge and treatment of acute illness, the need for more integrated, interdisciplinary approaches to understanding and treating chronic illness has become increasingly apparent in recent years.

The client’s experience of their illness journey can deeply impact their quality of life across multiple fronts.  A person’s innate desire for healing is energised by their sense of agency, creating psychological pathways of hope in seeking a cure.  This means being willing to trust and act on medical advice.  However, medical visits across different specialties, ambiguous diagnoses, disappointments and setbacks from treatments falling short of expectations, can all take an emotional toll.   Loss of normality in social, physical and occupational functioning, isolation and social withdrawal can lead to loss of purpose and meaning.  This can impact a person at an existential, or spiritual level, such that their sense of identity is affected. Psychiatric comorbidity, particularly depression, is a common feature of chronic illness, regardless of a person’s faith.  

Persistent Somatic Symptoms (PSS)

This paper focuses on a particular range of conditions characterised by common symptoms associated with persistent pain.  This includes:

• post-illness syndromes (e.g. viral/microorganism infection, chemical and mould exposure) that fall under diagnostic umbrellas of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), lyme disease and long-covid, and
• functional somatic syndromes (also known as disorders of gut-brain interaction) characterised by persistent pain and/or other somatic symptoms, e.g. irritable bowel syndrome (IBS), urological, chronic pelvic pain syndrome, functional neurological disorders, fibromyalgia and temporomandibular pain.

Whilst symptoms may be localised to specific organs or tissue, biomarkers do not necessarily inform aetiology. Furthermore, the association between symptoms, cause and biomarkers can progressively weaken as the condition progresses.² Conditions are aggravated by stress and characterised by inflammation, with potential wide-ranging effects on executive functioning (cognition, concentration, memory), sleep (circadian dysregulation), and vitality (metabolic function and energy/ATP regulation), all of which contribute to subjective symptom burden.  For example, ME/CFS is characterised by a hypo-metabolic state associated with energy/ATP dysfunction and symptoms of post-exertional malaise.^{3, 4}

Diagnostic systems such as the ICD-11 and DSM-5 classify illness according to distinct diagnostic boundaries (e.g. somatic, functional, mental).  However, the commonality of physical and psychiatric symptoms across persistent somatic disorders has exposed the limitations of traditional classification approaches.

Advances in translational research across the fields of neurobiology, cognitive and affective neuroscience have facilitated the development of a more concrete and systems understanding of underlying pathologies and mechanisms of action.  Consistent with the biopsychosocial framework, this knowledge brings with it opportunities for developing clearer, trans-diagnostic approaches to case formulation and treatment planning. Central sensitisation (CS) has been adopted as an umbrella term that recognises many of the common features.⁵   This paper explores the notion that CS may be a neurophysiological process that embodies a) dysfunctional mechanisms at play, and b) the generalisation effect of conditioned learning. 

The biopsychosocial model provides a useful organising framework for the purposes of explaining the illness trajectory, and distinguishing the respective event-related and process-related factors that underpin and maintain symptoms and distress.  Whereas past events can’t be changed, process-related factors represent the mechanisms of action that maintain the underlying dysfunction. If treatment interventions can target these more effectively, treatment may impact beyond providing symptom relief to effecting more sustainable change. This paper will focus on three areas:

a. Event-related factors:

(i) environment and experience – the relationship between early life adversity, trauma and stress vulnerability

b. Process-related factors:

(i) mind-body communication and interoceptive dysregulation

(ii) memory, learning and behaviour

Event-Related Factors

Environment, Experience and Stress Vulnerability

There is widespread recognition that adverse childhood experiences create vulnerability to stress and inflammatory effects associated with later onset of physical and mental illness.  A systematic review involving 85 studies across various countries found a significant association between adverse childhood experiences and the reporting of chronic pain conditions in adulthood.⁶ This appears to affect women more than men.  For example, women with a history of abuse are four times more likely to experience chronic pelvic pain in adulthood.⁷ Reports of abuse by close others are seven times greater in patients with interstitial cystitis than those with acute cystitis.⁸ Seng⁹ proposed that oxytocin alterations due to attachment dysregulation may contribute to maladaptive coping responses, manifesting as emotional dysregulation, impaired memory processing (including dissociation), somatisation and chronic smooth muscle dysregulation (a prominent feature of chronic pelvic pain, urinary pain and IBS).

Allostasis

Allostasis refers to self-modulatory neuroendocrine, autonomic, metabolic changes that enable bodily functions to adjust to environmental demands and maintain stability in the context of extreme or protracted stress.^{10, 11} This involves alteration of the operational parameters of biological systems via the hypothalamic-pituitary-adrenal (HPA) axis as the brain (Central Nervous System) evaluates and responds to environmental threats.  Allostatic load refers to the wear and tear the body experiences in attempting to adapt to prolonged stress. 

Research on the impact of adversity and psychosocial stressors such as loneliness, loss and uncertainty has established clear illness pathways whereby chronic stress and prolonged sympathetic nervous system activation produce an inflammatory response that alters gene expression, with an associated negative impact on immune system function and health. Social genomics researchers have coined the term Conserved Transcriptional Response to Adversity (CTRA) to describe the neuro-adaptive conditioning of the immune system toward a more pro-inflammatory stance.¹² Chronic stress in childhood can result in compromised early safety learning, whereby a state of vigilance and arousal becomes experienced as ‘normal’ and is undetected as a stress response in adulthood.

Dysregulation of the stress response produces cognitive, affective and behavioural responses marked by rigidity. These represent forms of maladaptive neuromodulation or conditioned learning, manifesting in common symptom patterns across a range of central pain syndromes. This ‘maladaptation’ can lead to secondary outcomes whereby biological markers of oxidative stress (inflammation) are manifested in various physiological systems (endocrine, gastrointestinal and enteric nervous systems).

Psychosocial stress is recognised as a major risk factor for somatic disease, due to the ‘wear and tear’ associated with prolonged physiological activity.  CTRA may therefore represent a cellular ‘biological signature’ that is communicated physiologically, psychologically and behaviourally as a learned script, characterised by an unconscious sense of threat and generalised sense of ‘unsafety’. Chemical and sensory signals are communicated to the brain via interoception (see below for further information).  However, it is up to the mind to do the sense-making (emotion-cognition) that shapes the ‘meta-narrative’ about what illness and pain mean and how they are to be faced.

Process-Related Factors

Whilst event-related factors as described above play a significant role in creating vulnerability to stress-related illness, interventions need to target the mechanisms that are maintaining the symptom experience.  Over recent decades a significant body of research has been focused on understanding the psychophysiological processes that underlie persistent pain conditions.  Generalised unsafety has been conceptualised as an implicit conditioned response, whereby the sympathetic nervous system reverts to a default, non-conscious “ON” state which becomes normalised over time.¹³ This is explored further below.

Mind-Body Communication: Interoceptive Dysregulation

The brain is responsible for the conscious perception of sensory stimuli (e.g. pain, hunger, thirst, temperature). Interoception refers to internal signalling pathways that allow the brain (via the insular cortex) to interpret physiological signals ascending from the body and to form mental representations of the state of the body. Interoception enables the brain to modulate (downward signalling) the biological, neuroendocrine and metabolic processes involved in the regulation of homeostasis. It is fundamental to internal and external threat detection and the activation of the stress response (sympathetic nervous system pathway).

The mental representations have been described as comprising three main sub-processes:

a) signal detection (e.g. heartbeat, pain),

b) self-evaluation (subjective perception of the level of sensitivity) and

c) meta-cognitive interpretation of what the signal means.

Interoceptive accuracy refers to the relationship between perceived and actual interoceptive signals.¹⁴

The functional effects of chronic inflammation have been found to increase neural activation of the cortical regions involved in interoception (insula, amygdala, anterior cingulate cortex).¹⁵ Interoceptive dysregulation has been found to be associated with a range of cognitive, emotional and behavioural responses, including amplified visceral sensitivity and increased perception of the pain threshold, anxiety, perseverative cognitions, social withdrawal, fatigue, lethargy and anhedonia.  The reported perception of pain may therefore represent the subjective sense of symptom burden and not necessarily the level of severity of the condition.  This requires sensitivity on the part of clinicians when exploring the patient’s symptom experience, to differentiate between their pain and suffering, respectively.

Interoceptive dysregulation is implicated in a range of chronic pain conditions such as fibromyalgia, IBS, chronic pelvic pain, interstitial cystitis, ME/CFS and is associated with a higher risk of psychiatric comorbidity.¹⁶ Resting Heart Rate Variability (HRV) is regarded as an indicator of autonomic imbalance, particularly reduced parasympathetic activity.  Resting HRV has been found to be a predictor of emotional instability, particularly positive affect.¹⁷ A meta-analysis covering 58 studies found lower reported HRV indices in patients with fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to healthy individuals.¹⁸ Resting HRV may be a reliable biomarker of interoceptive dysregulation, potentially useful as a psychophysical assessment measure.

Learning, Memory and Behaviour

Memory stores the learning from previous experiences and serves as a reference for making predictions about the future.  The “Better Safe than Sorry Strategy”¹⁹ has been used to describe the conditioning of the fear response, as characterised by an implicit, generalised assumption of unsafety, which in turn activates external and internal hypervigilance and an avoidant default coping response.  It proposes that the chronic stress response is a psychophysiological default state determined by automatic (bottom-up) processes that shape how safety is perceived and construed.  The implications are that the stress response is largely unconscious, i.e. perceived safety is the outcome of the brain’s prediction.  Psychological processes, such as perseverative cognition, strengthen the negative attribution bias, generating anticipatory anxiety at a conscious and unconscious level (e.g. disturbed or unrestful sleep).

Conditioned fear learning involves a self-reinforcing cycle of faulty interoceptive processing that is stored in long-term autobiographical memory. Faulty interoceptive processing leads to the sensitisation of pain memories, which are associated with abstract, non-contextualised mental representations. Sensory signals activate automatic fear-based responses.  This prevents new learning and acts as a barrier to recovery.  Interoceptive errors involve the following information processing deficits:

1. Working memory: perseverative cognition experienced as worry, rumination and reinforcing internal attention bias.
2. Abstract construal of sensory input which is generalised into one symptom report
3. Input from somatic and affective states is not well distinguished and contextualised, making the person feel more vulnerable.
4. Threat assessment: cognitive inflexibility associated with low discrimination between danger and safety cues.
5. Generalised, non-contextualised pain ‘scripts’ are stored in long-term autobiographical memory.  They contain implicit, self-limiting attributions (e.g. defectiveness, helplessness, failure) that reinforce loss of agency and lead to long-term negative side effects.

Generalisation is associated with a top-down command and control response via downward modulation of neural pathways in the central autonomic network (CAN), which creates the subjective experience of behavioural control over adverse events, with associated changes in motor-response programmes (e.g. avoidant coping).²⁰ This leads to enduring neuroplastic changes in the prefrontal cortex and compromised functional connectivity to ascending neural networks. As noted above, the Generalized Unsafety Theory of Stress proposes that prolonged stress responses are due to generalised and largely unconsciously perceived unsafety.  As such, the perception of stress is determined by subjective internal experience and isn’t necessarily dependent on the presence of external stressors.  This has implications for treatment planning.

Psychological Assessment and Case Formulation

Pain has a social and emotional context which contains the personalised narrative of a person’s symptom experience, including their beliefs (explicit and implicit) about the illness.  These factors influence the individual’s subjective state of weariness, sense of personal efficacy, level of ambivalence, expectations about treatment and potential for active engagement.  In considering these factors, medical assessment may need to consider whether psychological treatment is warranted as part of early intervention. Psychological assessment should seek to understand the biopsychosocial context, with the goal of developing a joint understanding between the client and clinician that provides an explanatory model of the presenting problems and points to a way forward.

Psychological self-report assessments of depression and anxiety (e.g. DASS42) may not be sufficiently sensitive to cases where psychological distress is manifested as a somatic experience, as is the case in many persistent pain syndromes.  The Patient Health Questionnaire (PHQ-15)²¹ and The Central Sensitisation Inventory (CSI)²² are examples of screening instruments that can provide a more informed understanding of psychological and somatic manifestations of stress.

Case formulation is an organic, iterative process that will benefit from an integrated, interdisciplinary approach between medical practitioners, psychologists and other allied health clinicians.  Given the practical challenges involved, this may be optimised by informative written communication, and case conferencing where necessary. 

Figure 1 below provides an example of the type of template that may be useful in psychological case conceptualisation.  It seeks to map the biopsychosocial components of the client’s illness experience, the functional consequences and the associated psychological mechanisms that form the basis of treatment planning.

Treatment Considerations

Treatment options fall into four broad categories:

a) pharmacological treatments and other medical interventions,

b) psychological treatments,

c) nutritional strategies that focus on improving the gut biome and reducing inflammation, and

d) other specific complementary treatments targeted towards reducing symptoms of ME/CFS, long-covid, mould toxicity, IBS, pelvic floor pain, etc.

The focus of this paper is on psychological treatment, with particular emphasis on a) the implicit nature of key maintaining mechanisms, as discussed above, and b) the relevance of heterogeneous, idiopathic factors that are an inevitable feature of the complexity of these disorders.

Treatment approaches that rely on top-down conscious mental processes may be insufficient in effecting change if the key maintaining mechanisms, as portrayed above, are a result of conditioned learning, stored in implicit dysfunctional memory and therefore outside conscious processing.  Treatment modalities such as eye movement desensitisation reprocessing (EMDR)²³ and clinical hypnosis²⁴ are aimed at targeting top-down mechanisms as well as modulating autonomic nervous system (ANS) activity and the neural circuits (thalamic-amygdala-hippocampal) involved in memory formation and consolidation. 

A recent clinical update on non-pharmacological approaches for inflammatory bowel disease, observed that patients who benefit most from cognitive behavioural therapy demonstrate psychological flexibility, which enables them to draw insights about how their thoughts and emotional states influence their experience of pain and level of suffering.²⁵ It was noted that patients with more visceral hypersensitivity find greater benefit from hypnotherapy, providing treatment is with a qualified clinician.

A person’s mentalisation or reflective functioning skills may be a factor that informs treatment planning.  Successful mentalising involves being able to maintain in conscious awareness the range of mental experiences (thoughts, emotions, memories) to make sense of one’s internal state, thereby creating a sense of internal coherence and agency.²⁶ Stress, trauma and dissociation impede mentalisation. If prior safety learning has led to emotional numbing and avoidance this may need to be addressed as part of psychological treatment.

The above considerations reflect the inherent complexity of transdiagnostic research in addressing the multivariate factors that are a prominent feature of persistent somatic symptom disorders.  SOMACROSS is an example of an inter-disciplinary research initiative focused on this objective.²⁷ Whilst this research continues, clinicians must manage the challenge of remaining up to date with research whilst using clinical judgement to make informed decisions regarding treatment. There are a range of psychological modalities, with demonstrated small to medium effect sizes that may be utilised in the management of persistent somatic symptom disorders ^{2, 24}.

The following is an outline of broad treatment goals that may form part of an integrated treatment approach, oriented toward ‘re-learning safety’, by working at the level of mechanisms of action, as portrayed in Figure 1 above.

Event-related:

• Desensitise and reprocess trauma-related memories to reintegrate dysfunctionally stored emotional, somatosensory and cognitive associations with adverse experiences.

Process-related:

• Focus on factors that promote the (unconscious) perception of safety rather than on situational stressors.
• Relearn ‘internal safety’ by modulating parasympathetic nervous system (PNS) activation.
• Improve reflective functioning and emotional regulation skills, expanding the time window for perceptual awareness of interoceptive signals and associated interpretation of cognitive-affective mental states.
• Improve threat detection and accuracy of perceived safety. 
• Incorporate imaginal and behavioural activation strategies to create ‘safety experiences’ from everyday experience (social connection, body fitness, environment/nature).
• Reinforce and consolidate generalisation of safety learning and associated functioning across broad life domains.

Spirituality

For Christians, spiritual issues can often sit in the background.  Mention was made earlier of the impact of chronic illness on identity, purpose and relationships.  This can extend to spirituality.  For some people, their relationship with God can provide a source of solace and strength.  For others, depression can create a sense of disconnection from God, and/or a sense of failure ( e.g. self-perceptions about lack of faith, lack of effort in evangelising), which may inhibit prayer and connection with other Christians.  Social situations can be anxiety provoking.  Well-meaning questions from others about the illness, treatment and recovery can be confronting, especially when there are no straightforward answers.  For some, this invokes a sense of failure, shame and loneliness. Clinicians who are informed regarding these sensitive issues can provide an important source of validation in recognising the physical, emotional and social demands of the illness.   Mutual understanding builds rapport and epistemic trust, which, regardless of the person’s faith, can create a sense of ‘being known’. 

Concluding Comments

This paper has sought to provide an overview of current developments in research and clinical practice that demonstrate how a biopsychosocial, transdiagnostic approach may assist in managing the inherent complexity of persistent somatic symptom disorders. Of relevance is the need to distinguish between event and process-related factors that form part of the illness trajectory, and which enable mapping of the mechanisms of action that hold potential for effective change via multi-disciplinary treatment approaches.  Sensitivity and understanding of the spiritual impact of the illness can provide a further source of encouragement for people navigating a difficult life journey.

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