Systems, personalised, precision medicine
Ethics, methodology and epistemology
Written by Dr Mark Ryan, Psychiatrist
The brain (more specifically, the microbiota-gut-brain axis) orchestrates homeostasis. Homeostasis is the correction of deviations outside a tight range of physiological functioning and activity necessary for health; it also orchestrates allostasis which refers to the process of adjusting physiological processes through change, and enables response to predicted challenges, enabling relevant physiological and behavioral responses. Allostatic overload refers to progressive adjustments to the point where the system is ‘strained’ and symptoms and illness emerge.
Typically, health assessments are limited to symptom profiling and categorical diagnostic labelling and then, application of a predominately pharmacologically based algorithm, often with polypharmacy. The treatment algorithm is based on population or group average data which simplifies the complexity of real-world conditions, fails to specify for the individual and for the important/essential role of clinical judgment and expertise. The outcomes of this methodology are generally limited and suboptimal with medication side effects being common. This suggests that co-morbidity may be a function of the model for understanding and identifying illness/disease categories. This in turn points to the need for a theory of observation (more on this later).
Psychiatric and physical illnesses are invariably associated with metabolic and physiological problems, which the medication-only approach fails to address, and may aggravate. Common manifestations of the physiological/metabolic issues include fatty liver, insulin insensitivity/type 2 diabetes, hypertension, elevated lipids, fatigue, gut symptoms, cognitive symptoms, inflammation, obesity, psychiatric, neurodegenerative, sleep, cardiac, and other diseases etc. This suggests that mental and physical health problems are not separate but more usually combined mental-physical problems. The various adjustments made in homeostasis/allostasis are inherent in our being-in-the-world, usually not apprehended unless we have a capacity to be subjectively attuned, and so often normalised until the ’downstream’ emergence of symptoms and identifiable pathology is apparent.
Everything is connected and our social world, life events and interpersonal relationships also involve our physiology and metabolism and thus homeostatic and allostatic processes. It is on this way that life events and experiences affect our physical and mental functioning. Interoception, ‘gut feelings’, felt sense, affective states and subjectivity are all terms that refer to the non-cognitive ‘information’ the gut-brain system uses in the homeostatic/allostatic adjustment process. In these ways the ‘body keeps the score’ of our life events and course through life to date, with emerging evidence that the microbiota-gut-brain axis is an important aspect of this dynamic.
The microbiota biomass has a systems-wide influence. Dysbiosis has been implicated in a wide range of illnesses including sleep(12;11), mood disorders(13;14;15), the stress response, adverse childhood experiences, Post Traumatic Stress Disorder (PTSD) (16;17;18), irritable bowel syndrome (IBS)(19;20), metabolic syndrome and non-alcoholic fatty liver disease(21:22;23). Dysbiosis has also been reported with SARS-CoV-2 infection(24;25;26), Attention Deficit Hyperactivity Disorder (ADHD)(27), Chronic Fatigue Syndrome (CFS)(28), obesity(29) and cardiovascular diseases(30;31).
Everything is also connected within. The microbiota-gut-brain axis refers to cross-talk in this axis - metabolic signaling, vagal nerve, enteric nervous system, immune system and blood borne neuroactive substances, influencing all cellular and other Central Nervous System (CNS) processes, microglia, astrocytes and blood-brain barrier permeability. A gut-brain network, comprised of a 0.05Hz gut rhythm entrains autonomic, sensorimotor and visuospatial neural networks in the brain.
From this perspective, we are a bioelectric network. Bioelectric networks and signaling are evolutionarily preserved and are involved in the integrated body-mind-world relationship and the emergence of intelligence and the cognitive mind. Transcranial magnetic stimulation influences this bioelectric network.
A systems model views symptoms as signifiers of dysregulation of homeostasis/allostasis. A systems medicine approach involves a ‘look under the hood’ approach for causal/driving/maintaining processes manifesting as the presenting and other symptoms. These processes are transdiagnostic – they occur across a wide range of diagnostic labels. Approaches and interventions aimed at these biomarkers of allostatic overload are intended to restore metabolic efficiency, recalibrate the allostatic system, and to re-establish functionality beyond only treating a symptom. Improved quality of life and wellbeing are thus more readily achievable outcomes than symptom reduction. From a systems perspective important transdiagnostic biomarkers include dysregulation of sleep-circadian sleep-wake rhythmicity and dysregulation of the gut-brain interactions with a complex systems interactions between both these biomarkers. The Research Domain Criteria (RDoC), specifies a look ‘under the hood’, as part of a systems assessment to assess patient-specific problems and to devise personalised treatments with the promise of outcomes beyond that achieved by standard diagnoses and generic treatments.
A systems approach is a necessary component of a personalised, precision medicine approach to both assessments and treatments. This is also a process of ‘seeing’ the patient as a person, a patient is much more than their diagnosis, but knowing the other requires paying close attention. Paying attention to others is seen by the philosopher Iris Murdoch as a moral issue, so that an inability/failure to attend to and see other people as they are, is an immoral act. In being immoral in this way, we unsee others, fail to ‘unself’, seeing them only from our perspective, not as they are/manifest themselves, thereby stereotyping, dismissing, ignoring, dehumanising them. Seeing the other is also a profoundly healing gesture. The various -sims, racism, sexism etc, are forms of ‘unseeing’ and the experiential impact of feeling dehumanised becomes more readily understandable.
This account of systems, personalised medicine is arguably a best practice methodology and epistemology. This is what we orientate to do at Cingulum Health with our multi-level, multi-modal assessments, interpersonal interactions and range of interventions.
