Reading: Mental health is the health of the whole body: How psychoneuroimmunology & health psychology can inform & improve treatment, Alessi & Bennett, 2019

Question 1

Proposed Thesis

Answer 1

Therapeutically targeting inflammation offers translational opportunities for integrating mental and physical healthcare, a key niche of the interdisciplinary field of health psychology.

Question 2

Immune activation & psychosis: a brief historical overview

Answer 2

o As early as the late 1800s, clinicians observed apparent links between immune activation and psychosis. Emil Kraepelin, the father of modern psychiatry, first documented cases of psychosis and other mental disturbances following contraction of influenza
o Psychotic disorders are also associated with an increased prevalence of autoimmune illnesses, a heterogenous group of over 70 diseases characterized by impaired tolerance to self- antigens and subsequent tissue damage and destruction

Question 3

Autoimmunity & mental disorders: evidence for shared biological mechanisms

Answer 3

o Autoimmune disorders commonly co-occur with a broad array of other psychiatric symptoms and conditions.
o Eg
 Schizophrenia & Celiac disease patients show a higher incidence of Major depressive disorder and Panic disorder
 Depressive symptoms are also very common in lupus
 And more

Question 4

 Immune dysregulation in depression

Answer 4

o In particular, low-grade chronic inflammation appears to play a role in the development of neuropsychiatric symptoms. Chronic inflammation has been most extensively studied in the pathophysiology of depression, in a theory known as the ‘cytokine hypothesis
o A causal role for inflammation in depression was first evidenced by observations that proinflammatory cytokine treatment induced a major depressive episode in up to half of patients
o Follow-up studies in both animals and humans demonstrate that exogenous administration of cytokines or cytokine inducers (e.g., endotoxins) leads to depressive symptoms, which can be prevented by prior anti-depressant treatment Additional immune alterations observed in major depressive disorder include reduction of natural killer (NK) cell activity and decreased number of lymphocytes such as B cells, indicating that immune dysfunction in major depression is associated with aspects of both immunosuppression as well as activation

Question 5

 Immune dysregulation in other mental disorders

Answer 5

o Altered cytokine profiles are observed in anxiety disorders, bipolar disorder, schizophrenia, and autism, as well as neurodegenerative disease

Question 6

 The nervous system, the immune system, & stress: a unifying framework

Answer 6

o It is now well-established that the brain and the immune system communicate bidirectionally, connected primarily through the autonomic nervous system and endocrine signaling of the HPA axis37. Peripheral cytokines affect the central nervous system by modulating neurotransmitter metabolism, activating the hypothalamic-pituitary-adrenal (HPA) axis, afferent vagal nerves, or directly crossing the blood- brain-barrier where it is highly permeable (e.g., circumventricular organs)
o HPA axis dysregulation is observed in many psychiatric conditions as well as autoimmune disorders38, implicating the role of dysregulated stress systems in immune and mental health. Cortisol, the hormone product of the HPA axis, is considered anti-inflammatory and typically suppresses the elevated immune response that occurs under conditions of acute stress39. However, when repeatedly activated by chronic stress, the body’s stress response systems are thought to become dysregulated and desensitized to their own feedback mechanisms, contributing to a low-grade inflammatory response37. Thus, chronic stress and increased stress reactivity can directly contribute to systemic inflammation and immune dysfunction.
o Stress has also long been recognized as playing a key role in the etiology and course of autoimmune diseases such as multiple sclerosis (MS). Higher environmental stress is positively associated with MS onset as well as course with exacerbations preceded by increased anxiety and depressive symptoms

Question 7

 Therapeutically targeting inflammation

Answer 7

o The cross-communication between the nervous and immune systems and their relationships with stress and gut health highlights the central role of inflammation as a common mechanism of disease
o Therapeutically targeting inflammation offers translational implications for integrating mental and physical healthcare at both the individual and community-level.

Question 8

 Therapeutically targeting inflammation ; Pharmacological interventions

Answer 8

 NSAIDS (non-steroidal anti-inflammatory drugs) as mono or adjunct immunomodulation therapies
* NSAIDs in animals have been shown to prevent HPA axis dysregulation, reduce cytokine levels in the hypothalamus and induce behavioural changes
 Other studies investigating the use of cytokine inhibitors to directly suppress inflammation demonstrate reduction of depressive symptoms in chronic inflammatory illness
 However, use of immunomodulating medications have known limitations, including low treatment adherence due to adverse side-effects like gastrointestinal bleeding and potential harm from long-term usage

Question 9

Therapeutically targeting inflammation ; o Dietary Interventions

Answer 9

 Lifestyle changes and behavioral interventions can offer safer, sustainable, and more cost-effective approaches for therapeutically targeting inflammation to both prevent and treat chronic mental and physical illness
 Diet can reduce inflammation – if the diet is low in refined carbs and added sugars and high in fruits and veges
 Intermittent fasting may also reduce inflammation
 Vitamentation with vit d a major modulator of the immune system may also help in reducing inflammation in patients with cystic fibrosis and reduce depressive symptoms
 Omega-3’s have also been looked into as a good adjunctive treatment for psychiatric conditions as they are anti-inflammatory. Mixed findings have been gained in regards to major depression and schizophrenia but omega-3’s do appear to have a protective effect against the development of mental illness
 Probiotic supplementation may also help reduce inflammation

Question 10

Therapeutically targeting inflammation ; Psychological Interventions

Answer 10

 Given the relationship between inflammation and stress, inflammation may also be indirectly targeted by modifying the perceptions and appraisals that initiate physiological stress responses.
 This could help reduce inflammatory levels by chronic HPA axis activation and help to increase recovery time between stressors
* Eg. CBT or mindfulness and acceptance-based approaches