Tag Archives: Epigenetics

DEPRESSION. It’s what’s Inside Your Head? – Johann Hari.

“Ask not what’s inside your head, ask what your head’s inside of” W. M. Mace.

“It is no measure of health to be well-adjusted to a sick society.” Jiddu Krishnamurti.

How does your brain change when you are deeply distressed? Do those changes make it harder to recover? The real role of genes and brain changes.

The distress caused by the outside world, and the changes inside your brain come together. If the world keeps causing you deep pain, of course you’ll stay trapped there for a long time, with the snowball growing, your genes are activated by the environment. They can be switched on, or off, by what happens to you.

Genes increase your sensitivity, sometimes significantly. But they aren’t, in themselves, the cause of depression. Your genes can certainly make you more vulnerable, but they don’t write your destiny.

Marc Lewis’s friends thought he was dead.

It was the summer of 1969, and this young student in California was desperate to block out his despair any way he could. He had swallowed, snorted, or injected any stimulant he could find for a week now.

After he had been awake for thirty-six hours straight, he got a friend to inject him with heroin, so he could finally crash.

When Marc regained consciousness, he realized his friends were trying to figure out where they could find a bag big enough to dump his body in.

When Marc suddenly began to talk, they were freaked out. His heart, they explained to him, had stopped beating for several minutes.

About ten years after that night, Marc left drugs behind, and started to study neuroscience. He became a leading figure in the field, and a professor in the Netherlands.

He wanted to know: How does your brain change when you are deeply distressed? Do those changes make it harder to recover?

If you look at a brain scan of a depressed or highly anxious person it will look different from the brain scan of somebody without these problems. The areas that relate to feeling unhappy, or to being aware of risk, will be lit up like Christmas tree lights. They will be bigger, and more active.

Fifteen years ago, if you had shown me a diagram of my brain and described what it was like, I and most people, would have thought: that’s me, then. If the parts of the brain that relate to being unhappy, or being frightened, are more active, then I’m fixed as a person who is always going to be more unhappy, or more frightened. You might have short legs, or long arms; I have a brain with more active parts related to fear and anxiety; that’s how it is.

Wrong. To understand why we have to grasp a crucial concept called neuroplasticity.

Your brain changes according to how you use it. Neuroplasticity is the tendency for the brain to continue to restructure itself based on experience. Your brain is constantly changing to meet your needs. It does this mainly in two ways: by pruning the synapses you don’t use, and by growing the synapses you do use.

For as long as you live, this neuroplasticity never stops, and the brain is always changing.

A brain scan is a snapshot of a moving picture. You can take a snapshot of any moment in a football game, it doesn’t tell you what’s going to happen next, or where the brain is going. The brain changes as you become depressed and anxious, and it changes again when you stop being depressed and anxious. It’s always changing in response to signals from the world.

Social and psychological factors have the capacity to physically change your brain. Being lonely, or isolated, or grossly materialistic, these things change your brain, and, crucially, reconnection can change it back.

We have been thinking too simplistically. You couldn’t figure out the plot of Breaking Bad by dismantling your TV set. In the same way, you can’t figure out the root of your pain by dismantling your brain. You have to look at the signals the TV, or your brain, is receiving to do that.

They, the distress caused by the outside world, and the changes inside the brain come together.

Once this process begins, it, like everything else that happens to us, causes real changes in the brain, and they can then acquire a momentum of their own that deepens the effects from the outside world.

Imagine that your marriage just broke up, and you lost your job, and you know what? Your mother just had a stroke. It’s pretty overwhelming. Because you are feeling intense pain for a long period, your brain will assume this is the state in which you are going to have to survive from now on, so it might start to shed the synapses that relate to the things that give you joy and pleasure, and strengthen the synapses that relate to fear and despair. That’s one reason why you can often start to feel you have become somehow fixed in a state of depression or anxiety even if the original causes of the pain seems to have passed.

While it’s wrong to say the origin of these problems is solely within the brain, it would be equally wrong to say that the responses within the brain can’t make it worse. They can. The pain caused by life going wrong can trigger a response that is so powerful that the brain tends to stay there, in a pained response, for a while, until something pushes it out of that corner, into a more flexible place.

And if the world keeps causing you deep pain, of course you’ll stay trapped there for a long time, with the snowball growing.

How much of depression is carried in your genes?

I had assumed I inherited it in my genes. I sometimes thought of depression as a lost twin, born in the womb alongside me.

Scientists haven’t identified a specific gene or set of genes that can, on their own, cause depression and anxiety, but we do know there is a big genetic factor.

Scientists studying the genetic basis for depression and anxiety have concluded that it’s real, but it doesn’t account for most of what is going on. There is, however, a twist here.

A group of scientists led by a geneticist named Avshalom Caspi did one of the most detailed studies of the genetics of depression ever conducted. For twenty-five years, his team followed a thousand kids in New Zealand from being babies to adulthood. One of the things they were trying to figure out was which genes make you more vulnerable to depression.

Years into their work, they found something striking. They discovered that having a variant of a gene called 5-HTT does relate to becoming depressed.

Yet there was a catch. We are all born with a genetic inheritance, but your genes are activated by the environment. They can be switched on, or off, by what happens to you.

If you have a particular flavor of 5-HTT, you have a greatly increased risk of depression, but only in a certain environment. If you carried this gene, the study showed, you were more likely to become depressed, but only if you had experienced a terribly stressful event, or a great deal of childhood trauma.

If those bad things hadn’t happened to you, even if you had the gene that related to depression, you were no more likely to become depressed than anyone else.

So genes increase your sensitivity, sometimes significantly. But they aren’t, in themselves, the cause of depression.

This means that if other genes work like 5-HTT, and it looks as if they do, then nobody is condemned to be depressed or anxious by their genes.

Your genes can certainly make you more vulnerable, but they don’t write your destiny.

For example, we know that even if you are genetically more prone to put on weight, you still have to have lots of food in your environment for your genetic propensity to put on weight to kick in. Stranded in the rain forest or the desert with nothing to eat, you’ll lose weight whatever your genetic inheritance is.

Depression and anxiety, the current evidence suggests, are a little like that. The genetic factors that contribute to depression and anxiety are very real, but they also need a trigger in your environment or your psychology. Your genes can then supercharge those factors, but they can’t create them alone.

Endogenous Depression?

Is there some group of depressed people whose pain really is caused in just the way my doctor explained to me, by their brain wiring going wrong, or some other innate flaw? If it exists, how common is it?

It used to be thought that some depressions are caused by what happened to us in our lives, and then there is another, purer kind of depression that is caused by something going badly wrong in your brain. The first kind of depression was called “reactive,” and the second, purely internal kind was called “endogenous.”

Scientists have studied people who had been hospitalized for reactive depressions and compared them to people who had been classed as having endogenous depressions. It turned out that their circumstances were exactly the same: they had had an equal amount of things happen to them to trigger their despair. The distinction seemed, to them at that time, based on their evidence, to be meaningless.

There’s no agreement and scant evidence that endogenous depression actually exists, but researchers generally agree that if it exists at all, it’s a tiny minority of depressed people. This means that telling all depressed people a story that focuses only on these physical causes is a bad idea.

There are however situations, in addition to manic depression and bipolar disorder where we know that a biological change can make you more vulnerable. People with glandular fever, or underactive thyroids, are significantly more likely to become depressed.

It is foolish to deny there is a real biological component to depression and anxiety, and there may be other biological contributions we haven’t identified yet, but it is equally foolish to say they are the only causes.

Why then do we cling to the idea these problems are caused only by our brains.

Junk Values. You can have everything a person could possibly need by the standards of our culture, but those standards can badly misjudge what a human actually needs in order to have a good or even a tolerable life. Our culture creates a picture of what you “need” to be happy, through all the junk values we have been taught, that doesn’t fit with what we actually need.

Get a Grip. For a long time, depressed and anxious people have been told their distress is not real, that it is just laziness, or weakness, or self-indulgence.

The right-wing British pundit Katie Hopkins said depression is “the ultimate passport to self-obsession. Get a grip, people,” and added that they should just go out for a run and get over their moaning.

The way we have resisted this form of nastiness is to say that depression is a disease. You wouldn’t hector a person with cancer to pull themselves together, so it’s equally cruel to do it to somebody with the disease of depression or severe anxiety. The path away from stigma has been to explain patiently that this is a physical illness like diabetes or cancer.

We have come to believe that the only route out of stigma is to explain to people that this is a biological disease with purely biological causes. So, based on this positive motive, we have scrambled to find the biological effects, and held them up as evidence to rebut the sneerers.
“See! Even you admit it’s not a disease like cancer. So pull yourself together!”

But does saying something is a disease really reduce stigma?
Everybody knew, right from the start, that AIDS was a disease. It didn’t stop people with AIDS from being horribly stigmatized. People with AIDS are still stigmatized, greatly stigmatized. Nobody ever doubted leprosy was a disease, and lepers were persecuted for millennia.

Professor Sheila Mehta set up an experiment to figure out whether saying that something is a disease makes people kinder to the sufferer, or crueller.

Believing depression was a disease didn’t reduce hostility. In fact, it increased it.

“This way is better”, Marc said, “because if it’s an innate biological disease, the most you can hope for from other people is sympathy, a sense that you, with your difference, deserve their big-hearted kindness.
But if it’s a response to how we live, you can get something richer: empathy, because it could happen to any of us. It’s not some alien thing. It’s a universal human source of vulnerability.

The evidence suggests Marc is right, looking at it this way makes people less cruel, to themselves and to other people.

Pills Pay Big

For decades, psychiatrists have, in their training, been taught something called the bio-psycho-social model. They are shown that depression and anxiety have three kinds of causes: biological, psychological, and social. And yet almost nobody I know who has become depressed or severely anxious was told this story by their doctor, and most were not offered help for anything except their brain chemistry.

Why? CASH!

It is much more politically challenging to say that so many people are feeling terrible because of how our societies now work. It fits much more with our system of neoliberal capitalism to say, “Okay, we’ll get you functioning more efficiently, but please don’t start questioning … because that’s going to destabilize all sorts of things.”

The pharmaceutical companies are major forces shaping a lot of psychiatry, because it’s this big, big business, billions of dollars.

They pay the bills, so they largely set the agenda, and they obviously want our pain to be seen as a chemical problem with a chemical solution. The result is that we have ended up, as a culture, with a distorted sense of our own distress.

Just defective tissue!?

Telling people their distress is due mostly or entirely to a biological malfunction has several dangerous effects on them.

You leave the person disempowered, feeling they’re not good enough, because their brain’s not good enough.

Secondly: it pitches us against parts of ourselves. It says there is a war taking place in your head. On one side there are your feelings of distress, caused by the malfunctions in your brain or genes. On the other side there’s the sane part of you. You can only hope to drug the enemy within into submission, forever.

But it does something even more profound than that. It tells you that your distress has no meaning, it’s just defective tissue.

This is the biggest division between the old story about depression and anxiety and the new story. The old story says our distress is fundamentally irrational, caused by faulty apparatus in our head. The new story says our distress is, however painful, in fact rational, and Sane.

You’re not crazy to feel so distressed. You’re not broken.

“It is no measure of health to be well-adjusted to a sick society.” Jiddu Krishnamurti.

from

Lost Connections. Uncovering the Real Causes of Depression and the Unexpected Solutions

by Johann Hari

get it at Amazon.com

DARK NIGHTS OF THE SOUL. Kidnapped by Depression – Dale M. Kushner * The Emotional Life of Your Brain – Richard J. Davidson, Ph.D. and Sharon Begley.

“We do not see things as they are, we see them as we are. Emotions, far from being the neurological fluff that mainstream science once believed them to be, are central to the functions of the brain and to the life of the mind.”

Why and how do people differ so widely in their emotional responses to the ups and the downs of life? How myths and neuroscience can illuminate the darkness of depression.

Imagine a black sack thrown over your head. Imagine your arms and legs bound, your body injected with a drug that wipes out thoughts, flattens feelings, and numbs senses. This is depression.

Depression is called the dark night of the soul for good reason. Depression leads us into the night world, a world of shadows, emptiness, and blurry vision. You feel lost, lonely and alone, mired in the quicksand of sadness, vulnerable to thoughts of failure and unworthiness.

During depression, we yearn for a lost part of ourselves, for it seems that our spirited aliveness has deserted us, our appetite for living kidnapped and dragged down into the house of death.

Depression may feel as if parts of us have died, and yet is it possible depression opens us to another level of deep experience, one that matures us and brings new wisdom?

We are more than our genetic predisposition and our biochemistry; we are conscious creatures capable of discovering light in the darkness.

“We do not see things as they are, we see them as we are,” says a Talmudic expression. Through the lens of depression, the world is saturated with gloom.

One way to understand the lived experience of depression is to see it acted out symbolically in story form. Myths and fairytales show us the collective (and archetypal) universal patterns of the human psyche. I may have “my depression” and you, “yours,” but throughout the ages, worldwide, depression has plagued the human race.

The Rape of Proserpina (1621-22), white marble sculpture, by Gian Lorenzo Bernini (1598-1680).
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One of the Greek Homeric hymns, the “Hymn to Demeter,” gives an early and vivid picture of depression. It tells the story of Persephone, Demeter and Zeus’s daughter, whom Hades, god of the underworld and brother of Zeus, falls in love with. When Hades asks Zeus’ leave to marry her, Zeus knows Demeter would never agree and says he will neither give nor withhold his consent. So, one day, while Persephone is gathering flowers in a meadow, the ground splits open and Hades springs forth and abducts her, dragging her down into his kingdom against her will. The unwilling bride screams to Zeus, her father, to save her, but he ignores her pleas. Demeter, a goddess herself, hears her daughter’s cries and also begs Zeus for aid, but he refuses to intervene.

Separated from her daughter, Demeter rages at the gods for allowing Persephone’s capture and rape. Her grief is “terrible and savage.” Disguised as an old woman, she roams the earth, neither eating, drinking, nor bathing while she searches for her child. During her time of mourning, the earth lies fallow.

“Then she caused a most dreadful and cruel year for mankind over the all-nourishing earth: the ground would not make the seed sprout, for rich-crowned Demeter kept it hid. In the fields the oxen drew many a curved plough in vain, and much white barley was cast upon the land without avail. So she would have destroyed the whole race of man with cruel famine.” “Hymn to Demeter,” translated from Greek by Hugh G. Evelyn-White.

Ceres Begging for Jupiter’s Help after the Kidnapping of Her Daughter Proserpine (1777) by Antoine-Frangois Callet (1741-1823).
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As Demeter pines for her daughter, so too, during depression, do we yearn for a lost part of ourselves, for it seems that our spirited aliveness has deserted us, our appetite for living kidnapped and dragged down into the house of death. With our instincts blunted, we sink into darkness, and experience the desolation of barren landscape. Like the grieving Demeter, our enthusiasm lost, our life-giving energy depleted, we fall into despair.

This feeling of isolation is a signature of depression and runs deep in those who try to articulate their condition and reach out for help.

As the story continues, Zeus’s mounting fear that if he does not reunite mother and daughter nothing will ever grow again on the land finally propels his intervention. He orders Hermes, messenger of the gods, into the underworld to bring Persephone back. Hades is surprisingly gracious in agreeing to her return. Inconsolable during her stay in the underworld, Persephone has yet to eat anything. Before she leaves, Hades urges her to eat at least three pomegranate seeds. Distracted by her joy at leaving, Persephone does so – and thereby consigns herself to return to Hades for three months every year. Had she not eaten the fruit of the underworld, she would have been able to stay with her mother forever.

When we enter the space of depression, it seems we will never “get out,” but as the myth reveals, nature is cyclic. The myth of Demeter and Persephone originates in ancient fertility cults and women’s mysteries, and is associated with harvest and the annual vegetation cycles. Symbolically, for a quarter of the year, while Persephone is in the underworld, lifeless winter prevails. When she returns to earth, spring advances, a time of rebirth.

But depressive cycles are not nearly as predictable as the seasons, and yet we might consider our time in the underworld as periods of incubation. While winter’s colorless landscape may suggest death, beneath the ground roots, seeds, and bulbs are dormant, not dead. They are busy with the business of storing nutrients for the coming season.

The Return of Persephone (1891), oil on canvas, by Frederic Leighton (1830-1896) shows Hermes returning Persephone to Demeter.
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For plants, winter’s stillness is necessary before spring’s renewal. Depression, too, can be viewed as a time of going inward and down into the depths, and can be a generative and creative interlude during which the psyche renews itself in the slower rhythms of dark days. Many artists attest to depressive episodes that prefigure a creative breakthrough. An astonishing number of famous artists, writers, and statesmen as diverse as Charles Darwin, Friedrich Nietzsche, Winston Churchill, Hans Christian Andersen, Abraham Lincoln, and Georgia O’Keefe have described experiencing depression.

Little is written about Persephone’s life in the underworld, but one thing is clear, she does not die. Quite the opposite. She is given the honorific title Queen of the Underworld. This suggests her movement “to below” is one of transformation and the acquisition of special gifts and powers. Depression may feel as if parts of us have died, and yet is it possible depression opens us to another level of deep experience, one that matures us and brings new wisdom?

When depression drags us away from the lively day world, we might remember Persephone. The darkness of the underworld may provide a special quality of illumination not possible in the glaring, horn-honking, digitally-frenzied daylight. To consider depression as an expression of loss, grief, mourning, and inevitability of mortality is to bring it into the realm of the human heart.

We are more than our genetic predisposition and our biochemistry; we are conscious creatures capable of discovering light in the darkness.

If myths allow us to look into “the heart of the matter,” then neuroscience allows us to peer into the actual matter of our brains. Dr. Richard J. Davidson, founder of the Center for Healthy Minds at the University of Wisconsin, Madison, has made it his life’s work to investigate brain (neuro)plasticity, and how we can improve our wellbeing through the development of certain skills, including meditation.

In his groundbreaking book, The Emotional Life of Your Brain: How Its Unique Patterns Affect the Way You Think, Feel, and Live—and How You Can Change Them, Dr. Davidson and his co-author Sharon Begley offer an in-depth view of how our brains respond to different emotions and provide strategies to help balance or strengthen specific areas of brain circuitry.

Schematic of brain regions that showed significantly different association with amygdala in control versus depressed individuals.
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The experience of depression differs from person to person. With the aid of fMRI imaging, Dr. Davidson has been able to pinpoint dysfunctional areas of the brain and correlate them with patient’s symptoms. Under the subheading “A Brain Taxonomy of Depression,”

Dr. Davidson identifies three subcategories of depression. One group of depressed patients had difficulty recovering from adversity while another group had difficulty regulating their emotions in a context-appropriate way. The third group was unable to sustain positive emotions. Different patterns of brain activity were noted for each group.

Dr. Davidson is optimistic. His book offers a questionnaire to help readers figure out their emotional “style” and gives exercises that build skills to improve brain functioning. Sufferers of depression need hope. Dr. Davidson’s excitement about what he is learning in the laboratory is palpable and his hope contagious.

Archetypal myths and brain science may seem disconnected, but each presents its own form of wisdom, one through images and story, the other through investigatory science. Demeter’s suffering, the barren land, Persephone’s descent into darkness lodge in our imagination and dreams and recommend that we look into our own lives to discover the source of our grief. Neuroscience advances our knowledge of brain anatomy and its relationship to our feelings and emotions. Each perspective provides a potentially valuable way to examine and understand our experience of depression.

Psychology Today

THE EMOTIONAL LIFE OF YOUR BRAIN. How Its Unique Patterns Affect the Way You Think, Feel and Live. And how You can Change Them.

Richard J. Davidson, Ph.D. with Sharon Begley

INTRODUCTION

A Scientific Quest

This book describes a personal and professional journey to understand why and how people differ in their emotional responses to what life throws at them, motivated by my desire to help people lead healthier, more fulfilling lives.

The “professional” thread in this tapestry describes the development of the hybrid discipline called affective neuroscience, the study of the brain mechanisms that underlie our emotions and the search for ways to enhance people’s sense of well-being and promote positive qualities of mind.

The “personal” thread is my own story. Spurred by the conviction that, as Hamlet said to Horatio, “there are more things in heaven and earth than are dreamt of” in the standard account of the mind provided by mainstream psychology and neuroscience, I have ventured outside the boundaries enclosing these disciplines, sometimes getting struck down, but in the end, I hope, achieving at least some of what I set out to do: to show through rigorous research that emotions, far from being the neurological fluff that mainstream science once believed them to be, are central to the functions of the brain and to the life of the mind.

My thirty years of research in affective neuroscience has produced hundreds of findings, from the brain mechanisms that underlie empathy and the differences between the autistic brain and the normally developing brain to how the brain’s seat of rationality can plunge us into the roiling emotional depths of depression.

I hope that these results have contributed to our understanding of what it means to be human, of what it means to have an emotional life. But as these findings accumulated, I found myself stepping back from the day-to-day life of my laboratory at the University of Wisconsin, Madison, which has grown over the years to something resembling a small company: As I write this in the spring of 2011, I have eleven graduate students, ten postdoctoral fellows, four computer programmers, twenty-one additional research and administrative staff members, and some twenty million dollars in research grants from the National Institutes of Health and other funders.

Since May 2010, I have also served as director of the university’s Center for Investigating Healthy Minds, a research complex dedicated to learning how the qualities of mind that humankind has valued since before the dawn of civilization, compassion, wellbeing, charity, altruism, kindness, love, and other noble aspects of the human condition, arise in the brain and how they can be nurtured.

One of the great virtues of the center is that we do not confine our work to research alone. We very much want to get the results of that research out into the world, where it can make a real difference in the lives of real people. To that end, we have developed a preschool and elementary school curriculum designed to cultivate kindness and mindfulness, and we are evaluating the impact of this training on academic achievement as well as on attention, empathy, and cooperation. Another project investigates whether training in breathing and meditation can help veterans returning from Afghanistan and Iraq cope with stress and anxiety.

I love all of this, both the basic science and the extension of our findings into the real world. But it is way too easy to get consumed by it. (I often joke that I have several full-time jobs, from overseeing grant applications to negotiating with the university bioethics committees for permission to do research on human volunteers.) I did not want that to happen.

About ten years ago, I therefore began to take stock of my research and that of other labs pursuing affective neuroscience, not the interesting individual findings but the larger picture. And I saw that our decades of work had revealed something fundamental about the emotional life of the brain: that each of us is characterized by what I have come to call Emotional Style.

Before I briefly describe the components of Emotional Style, let me quickly explain how it relates to other classification systems that try to illuminate the vast diversity of ways to be human: emotional states, emotional traits, personality, and temperament.

The smallest, most fleeting unit of emotion is an emotional state. Typically lasting only a few seconds, it tends to be triggered by an experience, the spike of joy you feel at the macaroni collage your child made you for Mother’s Day, the sense of accomplishment you feel upon finishing a big project at work, the anger you feel over having to work all three days of a holiday weekend, the sadness you feel when your child is the only one in her class not invited to a party. Emotional states can also arise from purely mental activity, such as daydreaming, or introspection, or anticipating the future. But whether they are triggered by real-world experiences or mental ones, emotional states tend to dissipate, each giving way to the next.

A feeling that does persist, and that remains consistent over minutes or hours or even days, is a mood, of the “he’s in a bad mood” variety. And a feeling that characterizes you not for days but for years is an emotional trait. We think of someone who seems perpetually annoyed as grumpy, and someone who always seems to be mad at the world as angry. An emotional trait (chronic, just-about-to-boil-over anger) increases the likelihood that you will experience a particular emotional state (fury) because it lowers the threshold needed to feel such an emotional state.

Emotional Style is a consistent way of responding to the experiences of our lives. It is governed by specific, identifiable brain circuits and can be measured using objective laboratory methods. Emotional Style influences the likelihood of feeling particular emotional states, traits, and moods.

Because Emotional Styles are much closer to underlying brain systems than emotional states or traits, they can be considered the atoms of our emotional lives, their fundamental building blocks.

In contrast, personality, a more familiar way of describing people, is neither fundamental in this sense nor grounded in identifiable neurological mechanisms. Personality consists of a set of high-level qualities that comprise particular emotional traits and Emotional Styles. Take, for instance, the well-studied personality trait of agreeableness.

People who are extremely agreeable, as measured by standard psychological assessments (as well as their own and that of people who know them well), are empathic, considerate, friendly, generous, and helpful. But each of these emotional traits is itself the product of different aspects of Emotional Style. Unlike personality, Emotional Style can be traced to a specific, characteristic brain signature. To understand the brain basis of agreeableness, then, we need to probe more deeply into the underlying Emotional Styles that comprise it.

Psychology has been churning out classification schemes with gusto lately, asserting that there are four kinds of temperament or five components of personality or Lord-knows-how-many character types. While perfectly interesting and even fun the popular media have had a field day describing which character types make good romantic matches, business leaders, or psychopaths, these schemes are light on scientific validity because they are not based on any rigorous analysis of underlying brain mechanisms. Anything having to do with human behavior, feelings, and ways of thinking arises from the brain, so any valid classification scheme must also be based on the brain. Which brings me back to Emotional Style.

Emotional Style comprises six dimensions. Neither conventional aspects of personality nor simple emotional traits or moods, let alone diagnostic criteria for mental illness, these six dimensions reflect the discoveries of modern neuroscientiflc research:

Resilience: how slowly or quickly you recover from adversity.

Outlook: how long you are able to sustain positive emotion.

Social Intuition: how adept you are at picking up social signals from the people around you.

Self-Awareness: how well you perceive bodily feelings that reflect emotions.

Sensitivity to Context: how good you are at regulating your emotional responses to take into account the context you fmd yourself in.

Attention: how sharp and clear your focus is.

These are probably not the six dimensions you would come up with if you sat down and thought about your emotions and how they might differ from those of others. By the same measure, the Bohr model of the atom is probably not the model you would come up with if you sat down and thought about the structure of matter. I don’t mean to equate my work with that of the founders of modern physics, only to make a general point: It is rare that the human mind can determine the truths of nature, or even of ourselves, by intuition or casual observation. That’s why we have science. Only by methodical, rigorous experiments, and lots of them, can we figure out how the world works, and how we ourselves work.

These six dimensions arose from my research in affective neuroscience, complemented and strengthened by the discoveries of colleagues around the world. They reflect properties of and patterns in the brain, the sine qua non of any model of human behavior and emotion.

If the six dimensions don’t resonate with your understanding of yourself or of those close to you, that is likely because several of them operate on levels that are not always immediately apparent. For example, we tend not to be consciously aware of where we fall on the Resilience dimension. With few exceptions, we do not pay attention to how quickly we recover from a stressful event. (An exception would be something extremely traumatic, such as the death of a child; in that case, you are all too aware that you have remained a basket case for months and months.) But we experience its consequences. For instance, if you have an argument with your significant other in the morning, you might feel irritable for the entire day, yet not realize that the reason you are snappish and grouchy and churlish is that you have not regained your emotional equilibrium, which is the mark of the Slow to Recover style. I will show you in chapter 3 how you can become more aware of your Emotional Styles, which is the first and most important step in any attempt to either gracefully accept who you are or transform it.

A rule of thumb in science is that any new theory that hopes to supplant what came before must explain the same phenomena that the old theory did, as well as new ones. In order to be accepted as a more accurate and all-encompassing theory of gravity than what Isaac Newton had proposed after he saw the apple fall from the tree (or not), Einstein’s general theory of relativity had to explain all of the gravitational phenomena that Newton’s did, such as the orbits of the planets around the sun and the rate at which objects fell to earth, and new ones, too, such as the bending of celestial light around a large star. Let me show, then, that Emotional Style has sufficient explanatory power to account for well-established personality traits and temperament types; later, particularly in chapter 4, we will see that it has a solid foundation in the brain, something other classification schemes do not.

I believe that every individual personality and temperament reflects a different combination of the six dimensions of Emotional Style.

Take the “big five” personality traits, one of the standard classification systems in psychology: openness to new experience, conscientiousness, extraversion, agreeableness, and neuroticism:

– Someone high in openness to new experience has strong Social Intuition. She is also very self-aware and tends to be focused in her Attention style.

– A conscientious person has well-developed Social Intuition, a focused style of Attention, and acute Sensitivity to Context.

– An extraverted person bounces back rapidly from adversity and thus is at the Fast to Recover end of the Resilience spectrum. She maintains a positive Outlook.

– An agreeable person has a highly attuned Sensitivity to Context and strong Resilience; he also tends to maintain a positive Outlook.

– Someone high in neuroticism is slow to recover from adversity. He has a gloomy, negative Outlook, is relatively insensitive to context, and tends to be unfocused in his Attention style.

While the combinations of Emotional Styles that add up to each of the big five personality traits generally hold true, there will always be exceptions. Not everyone with a given personality will have all the dimensions of Emotional Style that I describe, but they will invariably have at least one of them.

Moving beyond the Big Five, we can look at traits that all of us think of when we describe ourselves or someone we know well. Each of these, too, can be understood as a combination of different dimensions of Emotional Style, though, again, not everyone with the trait will possess each dimension. However, most people will have most of them:

– Impulsive: a combination of unfocused Attention and low Self-Awareness.

– Patient: a combination of high Self-Awareness and high Sensitivity to Context. Knowing that when context changes, other things will change, too, helps to facilitate patience.

– Shy: a combination of being Slow to Recover on the Resilience dimension and having low Sensitivity to Context. As a result of the insensitivity to context, shyness and wariness extend beyond contexts in which they might be normal.

– Anxious: a combination of being Slow to Recover, having a negative Outlook, having high levels of Self-Awareness, and being unfocused (Attention).

– Optimistic: a combination of being Fast to Recover and having a positive Outlook.

– Chronically unhappy: a combination of being Slow to Recover and having a negative Outlook, with the result that a person cannot sustain positive emotions and becomes mired in negative ones after setbacks.

As you can see, these common trait descriptors comprise different permutations of Emotional Styles. This formulation provides a way of describing what the brain bases for these common traits are likely to be.

If you read original scientific papers, it is easy to get the impression that the researchers thought of a question, designed a clever experiment to answer it, and carried out the study with nary a dead end or setback between them and the answer. It’s not like that. I suspect you realized as much, but what is not as widely known, even among people who gobble up popular accounts of scientific research, is how difficult it is to challenge a prevailing paradigm.

That was the position I found myself in during the early 1980s. At that time, academic psychology relegated the study of emotions mostly to social and personality psychology rather than to neurobiology; few psychology researchers were interested in studying the brain basis of emotion. What little interest there was supported research on the socalled emotion centers of the brain, which were then thought to be exclusively in the limbic system.

I had a very different idea: that higher cortical functions, particularly those located in the evolutionarily advanced prefrontal cortex, are critical to emotion. When I first suggested that the prefrontal cortex is involved in emotion, I was met with an endless stream of skeptics. The prefrontal cortex, they insisted, is the site of reason, the antithesis of emotion. It certainly could not play a role in emotion, too. It was very lonely trying to carve out a scientific career when the prevailing winds blew strongly in the other direction. My search for bases of emotion in the brain’s seat of reason was viewed as quixotic, to say the least, the neuroscientific equivalent of hunting elephants in Alaska. There were more than a few times, especially when I struggled to get funding early on, when my skepticism about the classic division between thought (in the highly evolved neocortex) and feeling (in the subcortical limbic system) seemed like a good way to end a scientific career, not begin one.

If my scientific leanings were a less-than-savvy career move, so were some of my personal interests. Soon after I entered graduate school at Harvard in the 1970s, I met a remarkable group of kind and compassionate people who, I soon learned, had something in common: They all practiced meditation. This discovery catalyzed my then rudimentary interest in meditation to such an extent that, after my second year of grad school, I went off to India and Sri Lanka for three months to learn more about this ancient tradition and experience what intensive meditation might bring. I had a second motive as well, I wanted to see whether meditation might be a suitable subject for scientific research.

Studying emotions was controversial enough. Practicing meditation was practically heretical, and studying it was a scientific nonstarter. Just as academic psychologists and neuroscientists believed that there are brain regions for reason and brain regions for emotions, and never the two shall meet, so they believed that there is rigorous, empirical science and there is woo-woo meditation, and if you practiced the latter, your bona fides for the former were highly suspect.

This was the period of The Tao of Physics (1975), The Dancing Wu Li Masters (1979), and other books arguing that there are strong complementarities between the findings of modern Western science and the insights of ancient Eastern philosophies. Most academic scientists dismissed this as trash; being a meditator in their midst was not, shall we say, the most direct path to academic success. It was made very clear to me by my Harvard mentors that if I wanted a successful scientific career, studying meditation was not a very good place to start. While I dabbled in research on meditation in the early part of my career, once I saw how deep the resistance was, I set it aside. I remained a closet meditator, though, and eventually, once I had been granted tenure at the University of Wisconsin, and had a long list of scientific publications and honors to my credit, returned to meditation as a subject of scientific study.

A big reason I did so was a transformative meeting I had with the Dalai Lama in 1992, which completely changed the course of both my career and my personal life. As I describe in chapter 9, the encounter was the spark that made me decide to bring my interests in meditation and other forms of mental training out of the closet.

It is breathtaking to see how much has changed in the short period of time that I’ve been at this. In less than twenty years, the scientific and medical communities have become much more receptive to research on mental training. Thousands of new articles are now published on the subject in top scientific journals each year (I was tickled that the first such paper ever to appear in the august Proceedings of the National Academy of Sciences was by my colleagues and me, in 2004), and the National Institutes of Health now provides substantial funding for research on meditation. A decade ago that would have been unthinkable.

I believe this change is a very good thing, and not because of any sense of personal vindication (though I admit it’s been gratifying to see a scientific outcast of a topic receive the respect it deserves). I made two promises to the Dalai Lama in 1992: I would personally study meditation, and I would try to make research on positive emotions, such as compassion and well-being, as central a focus of psychology as research on negative emotions had long been.

Now those two promises have converged, and with them my tilting-at-windmills conviction that the seat of reason and higher-order cognitive function in the brain plays as important a role in emotion as the limbic system does. My research on meditators has shown that mental training can alter patterns of activity in the brain to strengthen empathy, compassion, optimism, and a sense of well-being, the culmination of my promise to study meditation as well as positive emotions. And my research in the mainstream of affective neuroscience has shown that it is these sites of higher-order reasoning that hold the key to altering these patterns of brain activity.

So while this book is a story of my personal and scientific transformation, I hope it offers you a guide for your own transformation. In Sanskrit, the word for meditation also means “familiarization.” Becoming more familiar with your Emotional Style is the first and most important step in transforming it. If this book does nothing more than increase your awareness of your own Emotional Style and that of others around you, I would consider it a success.

CHAPTER 1

One Brain Does Not Fit All

If you believe most self-help books, pop-psychology articles, and television therapists, then you probably assume that how people respond to significant life events is pretty predictable. Most of us, according to the “experts,” are affected in just about the same way by a given experience, there is a grieving process that everyone goes through, there is a sequence of events that happens when we fall in love, there is a standard response to being jilted, and there are fairly standard ways almost every normal person reacts to the birth of a child, to being unappreciated at one’s job, to having an unbearable workload, to the challenges of raising teenagers, and to the inevitable changes that occur with aging. These same experts confidently recommend steps we can all take to regain our emotional footing, weather a setback in life or in love, become more (or less) sensitive, handle anxiety with aplomb . . . and otherwise become the kind of people we would like to be.

But my thirty-plus years of research have shown that these one-size-fits-all assumptions are even less valid in the realm of emotion than they are in medicine. There, scientists are discovering that people’s DNA shapes how they will respond to prescription drugs (among other things), ushering in an age of personalized medicine in which the treatments one patient receives for a certain illness will be different from what another patient receives for that same illness, for the fundamental reason that no two patients’ genes are identical. (One important example of this: The amount of the blood thinner warfarin a patient can safely take to prevent blood clots depends on how quickly the patient’s genes metabolize the drug.)

When it comes to how people respond to what life throws at them, and how they can develop and nurture their capacity to feel joy, to form loving relationships, to withstand setbacks, and in general to lead a meaningful life, the prescription must be just as personalized. In this case, the reason is not just that our DNA differs, though of course it does, and DNA definitely influences our emotional traits, but that our patterns of brain activity do. Just as the medicine of tomorrow will be shaped by deciphering patients’ DNA, so the psychology of today can be shaped by understanding the characteristic patterns of brain activity underlying the emotional traits and states that define each of us.

Over the course of my career as a neuroscientist, I’ve seen thousands of people who share similar backgrounds respond in dramatically different ways to the same life event. Some are resilient in the face of stress, for instance, while others fall apart. The latter become anxious, depressed, or unable to function when they encounter adversity. Resilient people are somehow able not only to withstand but to benefit from certain kinds of stressful events and to turn adversity into advantage.

This, in a nutshell, is the puzzle that has driven my research. I’ve wanted to know what determines how someone reacts to a divorce, to the death of a loved one, to the loss of a job, or to any other setback, and, equally, what determines how people react to a career triumph, to winning the heart of their true love, to realizing that a friend will walk over hot coals for them, or to other sources of happiness. Why and how do people differ so widely in their emotional responses to the ups and the downs of life?

The answer that has emerged from my own work is that different people have different Emotional Styles. These are constellations of emotional reactions and coping responses that differ in kind, intensity, and duration.

Just as each person has a unique fingerprint and a unique face, each of us has a unique emotional profile, one that is so much a part of who we are that those who know us well can often predict how we will respond to an emotional challenge.

My own Emotional Style, for instance, is fairly optimistic and upbeat, eager to take on challenges, quick to recover from adversity, but sometimes prone to worry about things that are beyond my control. (My mother, struck by my sunny disposition, used to call me her “joy boy.”)

Emotional Style is why one person recovers fairly quickly from a painful divorce while another remains mired in self-recrimination and despair. It is why one sibling bounces back from a job loss while another feels worthless for years afterward. It is why one father shrugs off the botched call of a Little League umpire who called out his (clearly safe!) daughter at second base while another leaps out of his seat and screams at the ump until his face turns purple.

Emotional Style is why one friend serves as a wellspring of solace to everyone in her circle while another makes herself scarce, emotionally and literally, whenever her friends or family need sympathy and support. It is why some people can read body language and tone of voice as clearly as a billboard while to others these nonverbal cues are a foreign language.

And it is why some people have insight into their own states of mind, heart, and body that others do not even realize is possible.

Every day presents countless opportunities to observe Emotional Styles in action. I spend a lot of time at airports, and it is a rare trip that doesn’t offer the chance for a little field research. As we all know, there seem to be more ways for a flight schedule to go awry than there are flights departing O’Hare on a Friday evening: bad weather, waiting for a flight crew whose connection is late, mechanical problems, cockpit warning lights that no one can decipher . . . the list goes on. So I’ve had countless chances to watch the reaction of passengers (as well as myself!) who, waiting to take off, hear the dreaded announcement that the flight has been delayed for one hour, or for two hours, or indefinitely, or canceled.

The collective groan is audible. But if you look carefully at individual passengers, you’ll see a wide range of emotional reactions. There’s the college student in his hoodie, bobbing his head to the music coming in through his earbuds, who barely glances up before getting lost again in his iPad. There’s the young mother traveling alone with a squirmy toddler who mutters, “Oh great,” before grabbing her child and stalking off toward the food court. There’s the corporate-looking woman in the tailored suit who briskly walks up to the gate agent and calmly but firmly demands to be rerouted immediately through anywhere this side of Kathmandu, just get her to her meeting! There’s the silver-haired, bespoke-suited man who storms up to the agent and, loud enough for everyone to hear, demands to know if she realizes how important it is for him to get to his destination, insists on seeing her superior, and-red-faced by now-screams that the situation is completely intolerable.

Okay, I’m prepared to believe that delays are worse for some people than for others. Failing to make it to the bedside of your dying mother is definitely up there, and missing a business meeting that means life or death to the company your grandfather founded is a lot worse than a student arriving home for winter break half a day later than planned. But I strongly suspect that the differences in how people react to an exasperating flight delay have less to do with the external circumstances and more to do with their Emotional Style.

The existence of Emotional Style raises a number of related questions. The most obvious is, when does Emotional Style first appear, in early adulthood, when we settle into the patterns that describe the people we will be, or, as genetic determinists would have it, before birth? Do these patterns of emotional response remain constant and stable throughout our lives? A less obvious question, but one that arose in the course of my research, is whether Emotional Style influences physical health. (One reason to suspect it does is that people who suffer from clinical depression are much more prone to certain physical disorders such as heart attack and asthma than are people with no history of depression.)

Perhaps most fundamentally, how does the brain produce the different Emotional Styles, and are they hardwired into our neural circuitry, or is there anything we can do to change them and thus alter how we deal with and respond to the pleasures and vicissitudes of life? And if we are able to somehow change our Emotional Style (in chapter 11 I will suggest some methods for doing so), does it also produce measureable changes in the brain?

The Six Dimensions of Emotional Style

So as not to leave you in suspense, and to make specific what I mean by “Emotional Style”, let me lay out its bare bones. There are six dimensions of Emotional Style. The existence of the six did not just suddenly occur to me, nor did they emerge early on in my research, let alone result from a command decision that six would be a nice number. Instead, they arose from systematic studies of the neural bases of emotion. Each of the six dimensions has a specific, identifiable neural signature, a good indication that they are real and not merely a theoretical construct. It is conceivable that there are more than six dimensions, but it’s unlikely: The major emotion circuits in the brain are now well understood, and if we believe that the only aspects of emotion that have scientific validity are those that can be traced to events in the brain, then six dimensions completely describe Emotional Style.

Each dimension describes a continuum. Some people fall at one or the other extreme of that continuum, while others fall somewhere in the middle. The combination of where you fall on each dimension adds up to your overall Emotional Style.

Your Resilience style: Can you usually shake off setbacks, or do you suffer a meltdown? When faced with an emotional or other challenge, can you muster the tenacity and determination to soldier on, or do you feel so helpless that you simply surrender? If you have an argument with your significant other, does it cast a pall on the remainder of your day, or are you able to recover quickly and put it behind you? When you’re knocked back on your heels, do you bounce back and throw yourself into the ring of life again, or do you melt into a puddle of depression and resignation? Do you respond to setbacks with energy and determination, or do you give up?

People at one extreme of this dimension are Fast to Recover from adversity; those at the other extreme are Slow to Recover, crippled by adversity.

Your Outlook style: Do you seldom let emotional clouds darken your sunny outlook on life? Do you maintain a high level of energy and engagement even when things don’t go your way? Or do you tend toward cynicism and pessimism, struggling to see anything positive? People at one extreme of the Outlook spectrum can be described as Positive types; those at the other, as Negative.

Your Social Intuition style: Can you read people’s body language and tone of voice like a book, inferring whether they want to talk or be alone, whether they are stressed to the breaking point or feeling mellow? Or are you puzzled by, even blind to, the outward indications of people’s mental and emotional states? Those at one extreme on this spectrum are Socially Intuitive types; those at the other, Puzzled.

Your Self-Awareness style: Are you aware of your own thoughts and feelings and attuned to the messages your body sends you? Or do you act and react without knowing why you do what you do, because your inner self is opaque to your conscious mind? Do those closest to you ask why you never engage in introspection and wonder why you seem oblivious to the fact that you are anxious, jealous, impatient, or threatened? At one extreme of this spectrum are people who are Self-Aware; at the other, those who are Self-Opaque.

Your Sensitivity to Context style: Are you able to pick up the conventional rules of social interaction so that you do not tell your boss the same dirty joke you told your husband or try to pick up a date at a funeral? Or are you baffled when people tell you that your behavior is inappropriate? If you are at one extreme of the Sensitivity to Context style, you are Tuned In; at the other end, Tuned Out.

. . .

from

The Emotional Life of Your Brain. How Its Unique Patterns Affect the Way You Think, Feel and Live. And how You can Change Them.

by Richard J. Davidson, Ph.D. and Sharon Begley

get it at Amazon.com

LOOKING BACK FROM DEATH ROW. A Gunman’s Regret – R. Douglas Fields * Study: Violent aggression predicted by multiple pre-adult environmental hits – Molecular Psychiatry.

Alternative Title: Adverse Childhood Experiences cause Epigenetic changes in the developing young Brain, leading to mental illness, depression, anger management issues, violent crime, incarceration and a multi generational vicious cycle of hopelessness and despair.

With only 5 percent of the world’s population, the United States has 25 percent of the world’s prison population. Why?

This study is the first to provide sound evidence, based on 6 separate cohorts, of a disease independent relationship between accumulation of multifaceted pre-adult environmental hits and violent aggression.

The name “correctional facility” is accurate from society’s perspective, but it is a delusional euphemism from the perspective of most inmates. According to the National Institute of Justice, three quarters of prisoners will be rearrested within five years of their release.

We lock up 7.16 out of 1,000 people in the United States, the highest rate of incarceration in the world.

The explosion of senseless mass violence in places that were once society’s most cherished communal places, schools, concert stadiums, public transportation and even houses of worship, is ripping apart the social fabric of American life.

The roots of violence at the level of brain biology need to be understood so that violence can be prevented.

Researchers have found a high incidence of genetic factors that increase impulsivity and anger in the violent prison population, and also an increased incidence of neurological abnormalities detectable with brain imaging. Studies of twins show that heredity accounts for over 60 percent of the risk for aggression.

The perpetrators of violent crime are almost always male. Humans have evolved through the survival-of-the-fittest struggle in the wild, evolved brain and bodily attributes that equip and predispose them to engage in aggression to provide and protect. This biological drive in males for aggression still exists in modern civilization.

Changes in society and in traditional male roles must be accompanied by new approaches to channel male aggression positively.

This can be reached by a path guided by neuroscience. Males have this biology of aggression for a reason, but it must be adapted to our current environment.

A new study finds that exposure to certain adverse events in early life, while the brain is undergoing maturation, greatly multiplies the odds of being institutionalized as an adult for violent aggression. They include poverty, social rejection from peer groups, cannabis and alcohol abuse, living in an urban environment, traumatic brain injury, immigration, conflict and violence in the home, and physical or sexual abuse.

. . . Scientific American

Molecular Psychiatry: Study

Violent aggression predicted by multiple pre-adult environmental hits.

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow up of matched extreme group individuals unexpectedly revealed that high risk subjects had 5 times greater probability of forensic hospitalization.

In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression.

Most strikingly, however, their accumulation strongly predicted violent aggression. An epigenome wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely. detemination in peripheral blood mononuclear cells of histone deacetylasel mRNA as ‘umbrella mediator’ of epigenetic processes revealed an increase in the high risk group, suggesting lasting epigenetic alterations.

Together, we provide sound evidence of a disease independent unfortunate relationship between well defined pre adult environmental hits and violent aggression, calling for more efficient prevention.

Introduction

Early exposure to external risk factors like childhood maltreatment, sexual abuse or head trauma, but also living in urban environment or migration from other countries and cultures, have long been known or suspected to exert adverse effects on individual development and socioeconomic functioning. Moreover, these environmental risk factors seem to contribute to abnormal behavior and to severity and onset of mental illness, even though different risk factors may have different impact, dependent on the particular neuropsychiatric disease in focus. On top of these ‘primary factors‘ that are rather inevitable for the affected, ‘secondary’, avoidable risks add to the negative individual and societal outcome, namely cannabis and alcohol abuse.

Adverse experiences in adulthood, like exposure to violence, traumatic brain injury, or substance intoxication, can act as single triggers to increase the short term risk of violence in mentally ill individuals as much as in control subjects.

However, comprehensive studies, including large numbers of individuals and replication cohorts, on pre-adult accumulation of environmental risk factors and their long term consequences on human behavior do not exist.

In a recent report we showed that accumulation of environmental risks leads to a nearly 10 year earlier schizophrenia onset, demonstrating the substantial impact of the environment on mental disease, which by far outlasted any common genetic effects. To search for epigenetic signatures in blood of carefully matched extreme group subjects of this previous study we had to re-contact them. This reconnect led to the unforeseen observation that high risk subjects had 5 times higher probability to be hospitalized in forensic units compared to low risk subjects.

This finding stimulated the present work: Having the longstanding concepts of sociologists and criminologists in mind, we hypothesized that early accumulation of environmenml risk factors would lead to increased violent aggression and social rule-breaking in affected individuals, independent of any mental illness. To test this hypothesis, we explored environmental risk before the age of 18 years in 4 schizophrenia samples of me GRAS (Göttingen Research Association for Schizophrenia) data collection. Likewise, risk factors were assessed as available in 2 general population samples.

In all cohorts, accumulation of pre-adult environmental hits was highly significantly associated with lifetime conviction for violent acts or high psychopathy and aggression hostility scores as proxies of violent aggression and rule breaking.

As a first small hint of epigenetic alterations in our high risk subjects, histone deacelylasel (HDACI) mRNA was found increased in peripheral blood mono nuclear cells (PBMC).

Fig. 1 Multiple environmental hits before adulthood predict violent aggression in mentally ill subjects as well as in the general population. Results from 6 independent samples.

a – Distribution of forensic hospitalization in the discovery sample (see results) suggested a substantial impact of environmental risk accumulation on violent aggression, a finding replicated in the remaining GRAS sample (GRAS I males and females minus extreme group subjects of the discovery sample). Note the ‘stair pattem’ upon stepwise increase in risk factors; stacked charts illustrate risk factor composition in the respective groups (including all risk factors of each individual in the respective risk group), Each color represents a panicular risk (same legend for dg and jk); b – Brief presentation of the violent aggression severity score, VASS, ranging from no documented aggression to lethal consequences of violent aggression with relative weight given to severity of aggression and number of registered re occurrences. c – Highly significant intercorrelation of violent aggression measures used in the present paper. d – Application of VASS to risk accumulation in the discovery sample; Kmskal Wallis H test (two sided). e-g – Schizophrenia replication cohorts 1: ‘stair pattem‘ of aggression proxy in risk accumulation groups: all 12 test (one sided). h – Comparative presentation of subjects (%) with violent aggression in risk accumulation groups across schizophrenia cohorts. i – Comparative presentation of subjects (%) with violent aggression before (pre morbid, ‘early’) or after schizophrenia onset (‘late‘) vs. individuals without evidence of aggression (‘no’) in risk accumulation groups of the discovery sample. j-k – General population replication cohorts IV and V: ‘stair pattern‘ of aggression proxies, LSRP secondary psy chopathy score (j) and aggression hostility factor of ZKFQ 50 CC (k) in risk accumulation groups; Kruskal Wallis 1 test (one sided). l – HDACI mRNA levels in PBMC of male extreme group subjects as available for analysis; Student‘s t test (one sided).

Discussion

The present work was initiated based on the observation in a schizophrenia cohort that accumulation of environmental risk factors before adulthood promotes the likelihood of later forensic hospitalization, interpreted as indicator of violent aggression. This interpretation and the effect of risk accumulation were consolidated using direct scoring of aggression over lifetime or, as aggression proxies, forensic hospitalization and conviction for battery, sexual assault, manslaughter or murder. or respective psychopathology measures in 4 independent schizophrenia cohorts and 2 general population samples. Importantly, our data support the concept of a disease independent development of violent aggression in subjects exposed to multiple pre adult environmental risk factors.

Whereas a vast amount of literature on single environmental risk factors reports consequences for abnormal behavior and mental illness, publications on pre-adult risk accumulation are scarce and mostly based on closely interrelated social/familial risk factors. Also, risk and consequence are often not clearly defined. Studies including larger, comprehensively characterized datasets and replication samples do not exist.

The present work is the first to provide sound evidence, based on 6 separate cohorts, of a disease independent relationship between accumulation of multifaceted pre-adult environmental hits and violent aggression.

The overall societal damage is enormous, and we note that mentally ill individuals who re-enter the community from prison are even more at risk for unemployment, homelessness, and criminal recidivism. These results should encourage better precautionary measures, including intensified research on protective factors which is still underrepresented.

In the psychosociological literature, the so called externalizing behavior in childhood includes hostile and aggressive physical behavior toward others, impulsivity, hyperactivity, and noncompliance with limit setting. The respective risk factors are all highly plausible, yet often theoretical, and derived from 4 broad domains: child risk factors (e.g., adverse temperament, genetic and gender risk), sociocultural risks (e.g., poverty, stressful life events), parenting and caregiving (e.g., confiict and violence at home, physical abuse), and children’s peer experiences (e.g., instable relationships, social rejection). A full model of the development of conduct problems has been suggested to include at least these 4 domains.

The risk factors analyzed in the present study are perhaps somewhat clearer defined but partially related to and overlapping across these domains. Urbanicity, migration, cannabis and alcohol reflect sociocultural input but also peer experience, and physical or sexual abuse belong to the parenting/caregiver aspect.

Certainly, there are many more, still undiscovered risk and numerous protective factors, potentially explaining why ‘only’ 40-50% of high risk individuals in our schizophrenia samples fulfill criteria of violent aggression.

We note that this study does not include genetic data analysis or correction for any genetic impact. The genetic influence on aggression, however, may be of considerable relevance for the individual, even though highly heterogeneous as for essentially all behavioral traits. Heritability of aggression, estimated from twin studies, reaches >60%. In fact, 50% of individuals with violent aggression upon pre-adult risk accumulation in the present study means another 50% without detectable aggression. This consistent finding across samples likely indicates that genetic predisposition is prerequisite for whichever behavioral consequence. Individuals without genetic predisposition and/or with more protective factors (genetic and environmental) may not react with violent aggression to accumulated environmental risk.

Importantly, the obvious gender effect may be a matter of degree rather than of pattern. In fact, the etiology of externalizing behavior problems is similar for girls and boys, as is the consequence of risk accumulation in the present study for males and females.

The risk factors of the sociological domains seem to be stable predictors over time, to some degree interchangeable, pointing to many pathways leading to the same outcome (principle of equifinality). The interchangeability is highly interesting also with respect to potential biological mechanisms. It appears that any of the here investigated hits alone, independent of its kind, can be compensated for but that higher risk load increases the probability of violent aggression.

Also for that reason, we are weighing risk factors equally in the present study. This could theoretically create some bias. However, to be able to estimate the true effect size of each specific factor separately on violent aggression and subsequently weigh all factors in a more proper way, much larger samples sizes would be needed that are presently not available anywhere in the world.

In contrast to the marginal influence of genome wide association data on mental disease in GRAS, the accumulated environmental impact on development of violent aggression is huge, reflected by odds ratios of >10. When striking at a vulnerable time of brain development, namely around/before puberty, the environmental input may ‘non specifically’ affect any predisposed individual. The hypothetical biological mechanisms underlying this accumulation effect in humans may range from alterations in neuroendocrine and neurotransmitter systems, neuronal/ synaptic plasticity and neurogenesis to changes in the adaptive immune system and interference with developmental myelination, affecting brain connectivity and network function.

Our approach to detect methylation changes in blood using an epigenome wide association scan was unsuccessful despite matched extreme group comparison, likely due to the small sample size, and perhaps the etiological/pathogenetic complexity of accumulated risks. Changes in brain, not accessible here for analysis, can certainly not be excluded. Interestingly, however, HDAC1 mRNA levels in PBMC of male extreme group subjects were increased in the high risk compared to the low risk group. This finding confirms peripheral HDAC1 mRNA levels as a more robust readout of epigenetic alterations in relatively small sample sizes, as compared to specific methylation sites in epigenome wide association scans or even in candidate genes. To gain further mechanistic insight and thereby develop in addition to prevention measures novel individualized treatment concepts, animal studies modeling risk accumulation seem unavoidable.

To conclude, this study should motivate sociopolitical actions, aiming at identifying individuals at risk and improving precautionary measures. Effective violence prevention strategies start early and include family focused and school based programs. Additional risk factors, interchangeable in their long term consequences, like urbanicity, migration, and substance abuse, should be increasingly considered. Health care providers are essential for all of these prevention concepts. More research on protective factors and resilience should be launched. Animal studies need to be supported that model risk accumulation for mechanistic insight into brain alterations leading to aggression, and for developing new treatment approaches, also those targeting reversal of epigenetic alterations. As a novel concept, scientific efforts on ‘phenaryptyping of the environment’, should be promoted to achieve more fundamental risk estimation and more effective prevention in the future.

*

Read the complete study here: Violent aggression predicted by multiple pre-adult environmental hits