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Connection, Compassion and the Genome

Posted on June 8, 2014 at 9:17 AM Comments comments (91)
Steve Cole, Phd one of the pioneer researchers in the new field of psycho-immunology, delivers the Meng Wu Lecture at CCARE Stamford University. Watch it here.

My transcript of Steve Cole's lecture: 

How we interact, how we connect has a tremendous influence on how our genes are expressed.  Traditionally we saw ethics, morality and the world of tangible, molecular biology of cells as very different worlds/domains. We are starting to see the shadow of each domain playing out in the other.
Gene expression and social factors

The genome isn’t expressing all its 20.000 genes at the same time. There is a lot of decision about which genes get expressed. The change of the activity of genes within our white blood cell is linked to
protracted, extended situations:
  • Low SES (social-economic status) 
  • Social Loss/ Anticipated bereavement
  • Post-traumatic stress
  • Cancer diagnosis
  • Social threat
  • Loneliness
  • Social instability
  • Chronic stress
  • Low social rank
  • Caregiving for seriously ill
  • Depression
  • Early life low SES
  • Poverty

The stress-response and the genome 

From a study by Irwin and Comle, Nature Reviews, Immunology, 2011
One of the major ways in which these experiences play on the genome is through the fight-flight stress response activated by the sympathetic nervous system, with the release of adrenaline (epinephrine) and noradrenaline (norepinephrine). Noradrenaline is released in the vicinity of a cell. Through its nteraction with receptors (ADRB2) on the surface of the cell the result is a pumped-up activity of genes involved in the expression of pro-inflamatory immune response genes and a stomping down of the activity of other genes (antiviral immune response genes).  

Through exposure to really overwhelming stress a second response kicks in – a defeat/withdrawal response, where your system shuts down, you are overwhelmed and your body hunkers down and just tries to survive. That response is mediated by a second hormonal pathway - the HPA (Hypothalamus - Pituitary - Adrenal). The hypothalamus tells your adrenal glands to produce more cortisol, which has a different impact on gene expression – it lowers the expression of antiviral immune response genes and lowers the expression of pro-inflammatory immune response genes.
Different experiences of the same event – either as a challenge that can be overcome or as something profoundly overwhelming is going to have different effects on my genome, it will evoke different kinds of biological response.

Studies by Cole et al. Proc Nat Acad of Sci USA, 2011 and Powell et al. Proc Nat Acad of Sci, USA, 2013
Our bodies are extremely dynamic at a cellular or molecular level. The average protein in the human body has a half-life of eighty days so that every single day we have to replace 1 – 2% of the proteins in our body and that process is open to ‘advice’ from the world outside the body, including the world that psychology creates in my mind. 

Gene expression can also catalyse the production of new cells (monocytes and dendritic cells which don’t live very long). This process is also orchestrated by changes in gene expression that are susceptible to regulation by the nervous system. In people who are confronting uncertain environments, the brain interprets those environments as threatening and activates these fight-and-fight responses. 

Norepinephrine signalling is delivered into the bone marrow in a form of a ‘piece of advice’ to the stem cell which says 'produce more myeloid cells: monocytes, granulocytes, dendritic cells'. As a consequence of that we have more of these cells going out into the body and circulating. For most of our development that made good sense but if there is nothing for those cells to respond to - because there is no physical injury and hence no bacterial infections. These cells are programmed to find trouble and do something about it. Some of the trouble they find might be the early stages of proliferation of cancer or damage to the wall of our blood vessels or minor damage in brain cells, all of which attracts these charged, primed immune cells. As these cells attempt to repair tissue damage but can inadvertently contribute to the sort of disease that nowadays are the true architects of our longevity . We no longer die of infectious disease, we now die of heart disease, cancer and neuro-degenerative diseases.


(Sloan et al. 2010 Cancer Research – done on a mouse injected with cancer cells and then confined to a small space – a stress inducing situation)
When animals have too many of these charged up monocytes in their body during the early stages of tumour-development they get many more cancer cells escaping from the initial tumour site and spreading out (metastasising). This is mediated by those immune cells, which having gone into the tumour to kill the microbes and repair damaged tissue. They liquify tissue so that the cancer cells can grow out, they help grow blood vessels into the tumour thus feeding it and suppress the rest of the immune system’s response to the growing cancer.
Psycho-social events alter our biology

We used to think of the brain and the immune system as separate it turns out that what is going on in the world has some association with what goes on in our body at a microbial level. Over millions of years our immune system has learned to listen to the chatter from the brain and if it hears indications that you are feeling substantially threatened it gets ready to deal wit tissue damage, whether tissue damage is happening or not and inadvertently it fertilisers diseases and becomes the architect of a host of problems.
-       Central nervous system: inflammation and neuro-degenerative disease
-       Vasculature: artherosclerosis
-       Lungs: URI, asthma
-       Lymphoid tissue: neoinnervation, HIV/SIV
-       Solid tumor in the breast, ovaries: metastasis
That is why so many different types of adversity (isolation, low SES, social threat, bereavement) seem to draw out disease. There are many different ways that humans have learned to feel threatened and stressed.

Attachment and isolation and how the body responds to stress

There are two different ways to run our bodies which correspond to two social genomic programs in immune cells. One operates in a world in which we are attached and safe, connected. In this the big threats that we confront are the diseases that travel from one to another (viruses). A separate modus operandi takes place in the context in which we are separated from our community or feel threatened within our community, which up-regulates these inflammatory genes which produce monocytes, geared to fight bacteria (in anticipation of tissue damage). It doesn’t help us as well because it fertilises chronic diseases.  
Hedonic versus eudaimonic happiness

What is the secret to making people feel genuinely safe? (Frederickson et al., PNAS, 2013) How should we live? What is the best way to thrive in human life? What is the nature of true happiness. Hedonic happiness: consuming happy experiences (Epicur). Eudaimonic happiness: satisfaction that derives from a deeper sense of making a contribution to a purpose or a group outside ourselves, a community, a cause, creation, discovery. It turns out that either eudaimonic or hedonic pursuits are correlated to low levels of depression, but when researchers asked the genome, eudaimonic happiness is correlated with healthy immune profiles whereas hedonic happiness is not.  

Compassion Based CBT workshop with Prof Paul Gilbert

Posted on January 9, 2014 at 12:09 PM Comments comments (0)
This is a workshop delivered by Prof Paul Gilbert at Palo Alto University in 2013 about the scientific premise and technique of Compassion Focused Therapy. 

Overview of Compassion Focused Therapy and the process of change with compassion. 

CFT is a psychological model, although it uses elements of CBT, humanistic and psychodynamic therapies. CFT started with Prof Gilbert's interest in patients who were struggling with standard therapies (diagnosis of Borderline Personality Disorder). These patients were focused on shame and self-criticism, which is linked to poor outcomes. He wanted to understand evolutionary mechanisms which maintained emotional problems. 

Cognitive Behaviour Therapy traditionally focuses on replacing on unhelpful thoughts and behaviour with helpful thoughts and behaviour. However some clients say they see the logic of the alternative thoughts but do not feel reassured or helped at the emotional level. They also say: "I know I am not to blame but I still feel to blame"

We need to feel congruent emotion in order for our thoughts to be meaningful to us. Emotions "tag" meaning onto experiences. In order to be reassured by the thought "I am loveable", this needs to be linked with the experience of 'being loveable'. Many patients who come from traumatic backgrounds have few memories of being loveable or soothed and thus may struggle to feel reassured and safe by alternative thoughts. 

Compassion focused therapy targets the activation of the soothing system so that it can be more readily accessed and used to help regulate threat-based emotions of anger, fear, disgust and shame. 

Evolutionary model of psychopathology 

We are an emergent species in the 'flow of life' so our brains, with their mechanisms for motives, emotions and competencies are products of evolution, designed to function in certain ways. 

Anxiety disorders are related to how cognitions trigger innate defences - fight, flight, demobilisation (Marks, 1987) or danger modes (Beck, 1996)

Depressions are related to evolved mechanisms for coping with defeats and loss (Beck, 1987; Gilbert, 1992)

Personality disorders are related to the under or over development of innate strategies (e.g. cooperation vs. competition) (Beck, Freeman et al. 1990; Gilbert, 1987)

The social circumstances of our lives, over which we have no control, have major implications for the kinds of minds we have, the way our genes become expressed, the kids of brains we end up with, the kind of person we become, the values we endorsed and the lives we live. 

How new psychologies emerged in the world
500 mil years ago - Reptilian psychology (territory, fear, aggression, sex, hunting)
120 mil years ago - Mammalian psychology (capacity for caring, group, alliance building, play, status)
2 mil years ago - Human psychology emerged (capacity for symbolic thought and self-identity, theory of mind, meta-cognition)
1 mil years ago - Human capacity for extended caring (looking after the old or the sick) 

Why we have complex brains and minds that are difficult to understand and regulate

The Old Brain: Emotions (anger, anxiety, sadness, joy, lust); Behaviours (fight, flight, withdraw, engage) Relationships (sex, status, attachment, tribalism)
New Brain: Imagination, fantasise, look back and forward, collating and integrating vast amounts of information from different modalities- sensory emotional, plan, ruminate. 
Social Brain: Need for affection and care 

The brain has a number of built-in biases. Biased learning (fear of snakes, heights). Biases can be implicit or explicit. We tend to be self-focused, kin-focused and exhibit in-group preferences. 

We have a capacity to become aware of being awareness. Mindfulness is the capacity to observe one's mind and it naturally calms us down. Compassion comes is a motivating system rooted in the caring system. Compassion has to be understood as an interaction - it depends also on the other being responsive to being cared for. 

The mind is primarily a social signalling system (See Tronick's 'still face' experiment, Joseph Campos experiment on the role of non-verbal communication guiding behaviour in babies) 

Humans have fundamentally have a desire to be helpful( Warneken and Tomasello experiments in compassion in babies). 

Evolutionary functional analysis 

There are three types of emotions, which act as motivators: 
-those that focus on threat and self-preservation
-those that focus on doing and achieving 
-those that focus on contentment and feeling safe. 

The threat system is the dominant system in your brain. It is designed to over-rule and switch off everything else. Attention becomes narrow-focused, scans for threats, moves towards thinking about what could go wrong. In anger and anxiety the body feelings overlap. Borderline patients are not able to distinguish between tension and anxiety. 

The role of the Anterior Insula in compassion

Posted on December 10, 2012 at 7:23 PM Comments comments (96)
Social emotions in social neuroscience: From emotion contagion to empathy and fairness (from 0:43:54) presented by Tania Singer from the University of Zurich at the 2012

Emotional contagion. Empathy. Theory of mind. 

Empathy is different from emotion contagion.  When we are empathic we are aware that the emotion that we experience is carried vicariously for the other, that they are the source of our affective state. A self-other distinction is important in the experience of empathy. In the case of emotion contagion we are unaware of the source of our emotion. All mammals exhibit emotion contagion.

Empathy is also different from cognitive perspective taking or "Theory of mind", which is a cognitive empathy. When we have "theory of mind" we have an abstract concept of the other person, we aware of the others'  thoughts but we don't share the affective state with the other person.  The brain circuits underlying these two routes to the understanding of the other are very different. In psychopathy the affective empathy missing.

Sympathy and compassion

Sympathy is feeling sorry that someone is experiencing a negative emotion, but not experiencing that emotion with the other. Sympathy can have a condescending aspect to it, it comes from a one-up position. Compassion is the appreciation that we are all on the same level, a deep understanding of connectivity and of the sameness of everyone. Compassion has a motivational element - wanting to help relieve the other of suffering.

There is an ontogenetic and phylogenetic sequencing between emotional contagion, empathy and compassion, which leads to prosocial behaviour. Emotion contagion developmentally precedes emotion and compassion. (Singer, 2006, Neuroscience behaviour review). Emotion regulation capacity, which reliant on the prefrontal cortex is related to the ability to understand another person. Young children have an "ego-centricity bias" that is they tend to be influenced by their own emotional state when judging the emotional state of another - they project their emotions onto the other. The prefrontal cortex allows us to inhibit our own emotional state and to come to an accurate understanding of the other as different from us (PFC is still being developed up to the age of 25 years old.)

There is an overlap activation in the anterior part of the Insula in experiencing a bad smell and watching someone experience a bad smell. There are also shared networks in the domain of pain for self and others. Researchers worked this out by observing couples. People who were asked to watch their partner experience pain showed the same brain activation in the Anterior Insula (AI) and Anterior Cingulate Cortex (ACC) as when they themselves experienced pain. (Singer, 2004, Science) 

The theory about the neuro-function of this activity

the Insula is the interoceptive cortex, which has the function of looking into the condition of your body, registering how you feel. The better the interoceptive awareness of one person the higher the size of the AI and the activity in the AI. Singer suggests that we we use representations of our own feeling state to make a model about what other people feel. To test this she turned to looking at the brains of people of Aperger's Syndrome and Alexithymia to investigate whether people who show deficits in understanding their own internal state also show deficits in interoceptive awareness and in the empathic understanding of another.

Alexithymia is characterized as a sub-clinical phenomenon, marked by difficulty in identifying and describing feelings and a tendency to focus on external events rather than inner experiences. Alexythimia is thought to characterize 10% of the typically-developing population. The estimated prevalance rate among patients wiht Asperger Syndrom is around 60-80%. Patients with ASD have a deficient in cognitive perspective taking. 

The results show that people who have a deficit in understanding their own emotions also have deficits in understanding the emotions of others - and there is a lack of activation in AI. Empathy training may concentrate first on training interoceptive awareness in the self. 

The results show that autism is not per se associated with a lack of empathy. It depends on the degree of alexythimia. Adolescents with Conduct Disorders have less grey matter volume in the AI, and show less empathy. (Sterzer et al., 2006) 

Modulating factors of empathy

Empathy is modulated by the intensity of emotions (love, hatred), relationship (familiarity, similarity, affective link), context (appraisal of the situation) as well as the gender, personality traits and emotional repertoire of the person who is empathizing. (Viznemont and Singer, 2006, TICS)

Empathy is modulated by fairness (Singer, 2006, Nature). We resonate with the pain of someone we like and are familiar with and less with someone we don't like or are unfamiliar with. We resonate with the pain of someone from our own group more. Fairness based motivation predicts revenge but compassion motivation doesn't produce the same pattern. Could we use compassion and equanimity training to reduce the incidence of conflict?

Singer wants to experiment with biofeedback - by showing subjects images of their activated insula and getting them to focus on increasing the activity in this part of the brain. She also wants to investigate the effect of compassion training on overall wellbeing. 

Cooperation and fairness

Both fairness and compassion based motivation can support cooperation in the case of positive reciprocity, that is when someone responds to fairness with fairness. Fairness based motivation leads to a breakdown in cooperation manifested as a a desire for revenge and punishment when norms are being violated. Punishment is somewhat helpful in maintaining cooperation in the case of lack of fair-play.

In compassion based motivation - generosity and forgiveness can counteract a desire for revenge buffer the decline into tit-for-tat pattern. (Batson and Ahmad, 2001). However those who are compassionate may be exploited, so some training in fairensess based motivation is important.

The affective states underlying fariness are fear and anger and underlying compassion are love and wish for the others' well-being. They have different impact on health.

Fact: Financial rewards kill motivation and creativity.

Posted on November 5, 2012 at 6:28 AM Comments comments (104)
Businesses are constantly overestimating the importance of financial reward in fostering motivation. It turns out that intrinsic motivation - doing things because we find it rewarding, meaningful and stimulating is more important when solving problems that require lateral thinking. Rewards kill creativity and productivity because the mind becomes focused on the reward rather than the problem/task itself. The higher the reward, the more it interferes with the successful engagement with the problem. 

Dan Pink advocates for self-direction and freedom of choice over how to do ones work. Some companies experiment with radical systems such as ROWE - results only work environments - that is an environment where an employee has total freedom and control over how they structure their work including when to show up at work and whether they take part in meetings, etc. In a ROWE environment management is redundant. 

Other research has shown that the more freedom one has over how they execute a task and how to organise our work, the more productive happy and motivated we are. The reverse is true - the less control we have over how to do our work, the more externally micro-managed our tasks are, the more stressed and unhappy we become.