Week 9- Psychoneuroimmunology Flashcards
Effect of smoking on telomere length
Smoking is associated with increased pace of telomere shortening
Pathogen Defined
A pathogen is defined as an organism causing disease to its host
Alessi and Bennet 2020; Mental health is the health of the whole body –> How PNI and health psyc can improve treatment
Background;
- Immunological dysfunction acts as a shared and common mechanism of both mental and physical illness
- eg. many psychiatric conditions have a higher prevalence in indivdiuals with autoimmune conditions (compared to the general population)
- eg. the link between chronic inflammation and depression
Proposed thesis;
- therapeutically targetting inflammation offers translation opportunites integrating metnal and phsyical healthcare, a key niche of the interdisciplinary field of health psychology
conclusion;
- we need to look at PNI treatments from an individual level and a community-wide prevention approach
- eg. could provide psychoeducation to patients and medical professionals about th elink between the immune system and mental/phsyical illnesses
-they suggest that targetting inflammation to treat mental illnesses is a valid strategy in addition to other psychological interventions (like ACT, CBT, talk-therapy, pharmacology etc etc)
- they also argue that psychologicla interventions can be used to decrease inflammation (like cbt and mindfulness), owing to the unique linkages between stress and the immune system. In fact, psychological interventions focussed on stress reduction have shown good efficacy in imporving immune function
They also proposed a framework for treatment on the indivdiual level up to community wide policies
Acute inflammation defined
arising from tissue or organ damage with fast onset and lasts a few days
Lecture summary
There is growing evidence that both chronic inflammation (especially in mid-life) and chronic stress throughout the lifespan is associated with shorter telomere length
Mechanisms linking chronic inflammation to telomere length are through redirection of bodily resources away from cellular repair; mechanisms linking chronic stress to telomere length are through chronic elevations of the HPA-axis (via cortisol) leading to increased oxidative stress and reductions in telomerase
Shorter telomeres create a shorter lifespan because the cells become unstable during replication and lead to earlier cellular death
List the two main branches of the immune system
- innate immune response
- this is the ‘dumb’ immune system
- it is non-specific to particular viruses
- it is also quick - adaptive immune response
- is able to learn and improve it’s repsonse over time
- it is specific to certain viruses
- is slow to start
Emotional Styles and Colds - Cohen 2003
Sample; 334 healthy volunteers aged 18-54
Method; a viral challenge
- they assessed people’s tendency to experience positive emotions (energetic, happy, related) and negative emotions (hostile, anxious, depressed) via repeated nightly telephone survey on 3 nights in previous week
- in quarantine, gave nasal drops containing two rhinoviruses and monitored in quarantine for the development of the common cold
- They measured objective cold symptoms (mucus production from collected tissues) and subjective cold symptoms (suveys about symptoms like congestion and sore throat severity) surveyed and averaged over the next 5 days
- Their research question was; Does emotional style alter resistance to the common cold
Findings;
People who scored highly on positive emotion style (happy people) had lower objective and subjective symptoms
People who scored highly on negative emotion styles (slightly neurotic people) had no difference to others but on subjective cold symptoms they scored higher (so they felt sicker but weren’t)
Ifnlammation and depression study - Shuang Bai et al., 2020
- a meta-analysis of 30 RCTs testing anti-inflammatory agents (non-steroidal anti-inflammatories like NSAIDS eg. ibuprofen/nurofen/advil); omega-3 fatty acids; cytokine inhibitors; statins; corticosteroids; minocycline; pioglitazone; modafinil and N-acetylcysteine
Participants with major depressive disorder. Were given either anti-inflammatory or placebo, as a mono-therapy or in a combination with traditional antidepressants for 4-16 week trials
Results;
- Anti-infalmmatory agents had a larger reduction in depression score than placebo; stronger when used as adjunctive treatment; weaker effects in women-only trials; weakest effects (but still significant) for Omega-3 Fatty acids and strongest for NSAIDS
Prople treated with anti-inflammatory agents showed a larger remission rate than placebo. Remission is good - it means a person has not become depressed again in the follow-up period (months to years)
Bidirectional Relationship Between Inflammation and Depression and anti-inflammatory treatment
There is growing evidence that we can target inflammation to decrease mental health symptoms
we can do this by ;
- pharmacology - aka administering anti-inflammatory agents
- through lifestyle interventions including anti-inflammatory diets. Therefore, inflammation may be a mechanism for why healthy diets prospectively predict lower incidence of depression
Inflammation and Depression
Chronic inflammation has been found ina variety of psychiatric conditions (such as depression and anxiety)
- pro-inflammatory cytokines elevated in depression
- evidence that ifnlammation underlies or contributes to depression via reduced neurogenesis (lower brain derived neurotrophic factors, BDNF, in hippocampus) as well as heightened neurotoxicity, and accelerated activity of the HPA-axis - which drives high corsol
There is evidence for both a prospective and longitudenal relationship whic indicates causality
Psychoneuroimmunology (PNI)
= a relatively new field of study that investigates the interaction between psychological, neurological, and immune system processes.
PNI considers how brains, beahviour and immune system interact.
The field of PNI “Challenges the biomedical concept of the immune system as an ‘autonomous’ defense system”
Chronic Inflammation vs Chronic Stress for shortening telemores
Chronic inflammation;
- can accelerate telomere shortening through various mechanisms (increased DNA damage, ‘adverse biochemical environment”, - Epel 2009 and reducing activity of telomerase.)
Chronic Stress;
- can also accelerate telomere shortening via HPA-axis; stress increases activation of cortisol, which increases glucose metabolism and production of reactive oxygen species (free radicals), which damage cells and impair the ability of cells to repair damage
- rapid biological aging through telomere shortening is another mechanism for how chronic inflammation and chronic stress affect health and longevity
Chronic inflammation
Arising from more complex factors with slower onset that lasts months or years. Can arise form an infection,e xposure to an irrtant for long periods, auto-immune disorders, oxidative stress, aging, obestiy, and lifestyle factors (Big-5 health behaviours, poor sleep). In this circumstance the body maintains an inflammatory response even when there is no outside danger
Epel et al., 2004
- is a seminal paper on the role of stress on telomere shortening
Method;
- 58 healthy mothers of a healthy or chronically ill child
- they measured subjective stress (with the PSS) and objective stress (number of years of caregiving)
- Measired telomeric length and telomerase enzyme (from blood) and oxidative stress (from urine)
They found that the longer people had been caring for their kids (so the more stress they had) the shorter their telomeres and the less active their telomerase
Discussion;
- chronic life stress (both subjective and objective) predicted important molecular markers of cell senescence and longevity (via telomere length, telomerase activity and oxidative stress)
- high stress mothers had telomeres shorter by the equivalent of 9-17 years of additional aging compared to low stress mothers
Inflammation defined
Inflammation is part of the body’s defence mechanism. It is the process by which the immune system recognises and removes harmful and foreign stimuli and begins the healing process.
Inflammation can be acute or chronic
Idea and Application of Immune Function and Inflammation and Stress
- Psychological factors that affect stress also immune system function
- therefore, intra-individual factors like hostility and emotional style should also affect the immune system
Measuring Inflammation
we can measure;
1. pro-inflammatory cytokines (like TNF and interleukins) which are involved in initiating an inflammatory response in response to pathogen - which can be measured with a blood draw
- c-reactive protein (CRP) substance produced in liver in repsonse to acute inflammation but al also sensitive to chronic inflammation
What is inflammation and what does the inflammatory response consist of
The inflammatory response is a complex biological reaction to injury or infection aimed at eliminating harmful stimuli and promoting tissue repair.
Neutrophils are the first immune cells to arrive at the site of infection or injury and play a key role in engulfing and destroying pathogens.
Macrophages follow and help clear debris and pathogens, while also releasing signaling molecules to regulate the immune response.
Natural killer cells are specialized lymphocytes that target and kill infected or abnormal cells, helping to control infections and prevent the spread of disease.
Difference in types of inflammation and their use
Short term inflammation is good, because it signals to our immune cells where the infection is and helps us to repair tissues
but chronic inflammation means our body is always in ‘alert’ which can damage tissues
chronic inflammation may also hasten the rate at which a person ages
- proinflammatory cytokines (like CRP) shut down ‘long-term’ building projects such as cellular repair
- this can impact the length of telomeres which links to the rate of aging
Things the immune system needs to do (4)
- Recognise what is a pathogen
- Acknolwedge that pathogens are dangerous
- Recognise what isn’t a pathogen
- Initiate the appriate response to tackle the virus or pathogen
Timeline aka the History of PNI
1919; Ishigami published a paper suggesting that negative emotions could influence the immune systems of patients with tuberculosis (so more negative emotions = higher stress = poorer recovery from tuberculosis)
1920’s; students of pavlov conducted studies showing that classical conditioning could affect the immune response
- so we can condition the immune system in animals
- in these studies animals would get heat applied or a scratch on their arm then apply immune activating drug which caused inflammation. Then found that over time simply the application of heat or the scratch would cause the inflammatory response
1950’s-60s; some studies suggest psychological stress increase susceptibility to infection
1981; the term PNI first appears
Inflammation and Depression
- There is growing evidence that we can target inflammation to decrease mental health symptoms
> Through pharmacology - anti-inflammatory agents
What about through lifestyle factors, such as diet? Anti-inflammation diet fruit and vege consumption association with decreased inflammation; processed diets (refind carbs and added sugars) associated with increased inflammation
What does the innate immune response consist of
consists of;
- external barriers; like skin and mucous membranes
- internal defenses; inflammation, chemical signals, fever
Symptoms of the acute immune response
- redness
- swelling
- heat
- pain
these are designed to immobilise the pathogen
Acute Stress Enhances the Immune Response
- during the first 20-30 mins of stress parts of the immune response is upregulated/enhanced
- in particular, the innate immune response
- more cells are sent into circulation
- more neutrophils, macrophages and natural killer cells are sent ot the site of inflammation
SAM system activates the immune system but the HPA activation and cortical reduce immune activity
Once the HPA system is active, immunosupression begins to occur via cortisol’s effects of suppressing the immune system
- the effect of cortisol should bring the system back to it’s baseline functioning, but in chronic stress inflammation and high cortisol results in an overshoot and the immune system down-regulates too much
Hostile Marriages and Wound Healing - Kiecolt-Glaser and Loving 2005
Sample; 42 healthy marriage couples ages 22-77, married for a mean of 12.55 years
Method;
- completed questionnaires about relationship
- baseline blood samples were taken, then a vaccum pump was used to induce blisters on the arms
- on the first visit couples had a social support interaction whilst blood was taken to measure cortisol levels
- on the second visit discussed a marital disagreement whilst blood was taken to measure cortisol levels
They then measured the time it took for the blisters to recover and heal
Results;
- blister wounds healed more slowly, and cytokine production was lower at wound sites after martial conflict and after ‘social support’ interacions
- ‘hostile’ couples healed at 60% of the rate than ‘low hostile’ couples across both interactions (and an extra 2 days of healing required)
The role of chronic stress in suppressing the immune response
- glucocorticoids (cortisol) can shrink the thymus; halt the maturation of T cells; makes T cells less responsive; can induce apoptosis in T-cells
- therefore, chronic stress can make people more susceptible to infection over time because the immune system is suppressed
Healthy Diet - aka anti-inflammatory Diet
Is similar to the mediterannean diet - is high in unprocessed foods including fruit and veges, nuts, legumes, olive oil, fish, eggs, beans etc
There is a prospective relationship between fruits and veges and mental health;
- with moderate adherence to the mediterranean diet having the greatest effect on reducing incidence of depression
- People who eat more pro-inflammatory foods (or ultraprocessed foods) have a curvilinear relationshp with every increase in UPF (per 100g) having an increase in depression risk before it levels out
Stats on inflammation and depression
~25% of people with infalmmation have depression
1/3 of people with depression have inflammation
Role of inflammation
Short term inflammation is good, because it signals to our immune cells where the infection is and helps us to repair tissues
but chronic inflammation means our body is always in ‘alert’ which can damage tissues and cause rapid cellular aging
Telomeres
Telomeres are protective ‘non-coding’ caps of DNA at the ends of the chromosome strands. With every cell division telomeres shorten. Thelomeres that are too short destabilise DNA replication (and therefore protein production) which leads to the death of that cell (senescence)
- Telomeres shorten with biological age because each time a cell divides, telomere caps become shorter.
- Telomere length is a biomarker of biological aging
- Telomerase can replenish telomere caps, but only in certain types of cells (stem cells, germ cells, immune cells)
- Chronic stress and inflammation can increase the rate of Telomere shortening
