Lost Connectionscover

Johann Hari

Lost Connections

Quotes and Notes - November 21st, 2022

Against depression as a chemical imbalance, against anti-depressants as treatment

Against drug trial data

Drug companies have an incentive to sell drugs, regardless of how effective they are. They conduct scientific studies and secrets, and only publish results that makes their drug look good - or the drugs of their competitors look bad. It's why coca-cola would never publish any study showing sugary black colored water is not good for you, or why KFC would never release any information telling you that fried chicken isn't the healthiest food you can eat.

Of all the studies drug companies carry out, 40 percent are never released to the public, and lots more are only released selectively, with any negative findings left on the cutting room floor.

The Hamilton scale is a measurement scientists use to determine someone's level of depression. It was invented by a scientist named Max Hamilton in 1959 and it ranges from 0 (you're bopping and hopping) to 51 (you're hopping in front of trains).

Irving Kirsch is one expert that looked at the real data behind anti-depressants and found that there's little evidence to support drugs as a treatment for depression. Through freedom of information requests he was able to get all published an unpublished drug trial data for most anti-depressants tested in the US. He found that in the real data that hadn't been run through a PR filter, antidepressants do cause an improvement in the Hamilton score - they do make depressed people feel better - but it's only a 1.8 point increase, by contrast, improving your sleeping patterns yields an improvement of 6 points - not exactly glowing numbers in favor of antidepressants.

Against low serotonin as a cause for depression

I went to see one of the first scientists to study these new antidepressants in Britain, Professor David Healy, in his clinic in Bangor, a town in the north of Wales. He has written the most detailed history of antidepressants we have. When it comes to the idea that depression is caused by low serotonin, he told me: There was never any basis for it, ever. It was just marketing copy. At the time the drugs came out in the early 1990s, you couldn't have got any decent expert to go on a platform and say, ‘Look, there's a lowering of serotonin in the brains of people who are depressed' … There wasn't ever any evidence8 for it. It hasn't been discredited, he said, because it didn't ever get ‘credited,' in a sense. There wasn't ever a point in time when 50 percent of the field actually believed it. In the biggest study of serotonin's effects on humans, it found no direct relationship with depression. Professor Andrew Skull of Princeton has said attributing depression to low serotonin is deeply misleading and unscientific.

There's no evidence that there's a chemical imbalance in depressed or anxious people's brains, Professor Joanna Moncrieff - one of the leading experts on this question - explained to me bluntly in her office at the University College of London. The term doesn't really make any sense, she said: we don't know what a chemically balanced brain would look like

The argument for anti-depressants

Dr. Peter Kramer is one expert heavily in favor of anti-depressants. Some arguments he makes against Irving's data analysis:

  • Not giving drugs enough time to work (most trials run for 4 to 8 weeks)
    • There were two long term studies that Irving found - in one the placebo did the same as the drug, in the other, the placebo did better
  • Drug trials mix moderately and severely depressed people, and it's likely that drugs work best on severely depressed people
    • In Irving studies, with the exception of one, all studies were of people classified as suffering from severe depression
  • Drug trials are bullshit
    • While you can make an argument for bias and negative self-selection in drug trials, if the data is bullshit, then surely administering drugs on the basis of either bullshit data or no data is not a particularly powerful argument?

Very few scientists now defend the idea that depression is simply caused by low levels of serotonin, but the debate about whether chemical antidepressants work—for some other reason we don't fully understand—is still ongoing. There is no scientific consensus. Many distinguished scientists agree with Irving Kirsch; many agree with Peter Kramer.

The grief exception

The way doctors are supposed to diagnose depression, in the United States, is laid out in the Diagnostic and Statistical Manual (DSM). To get a diagnosis of depression you have to show at least five out of nine symptoms nearly every day.

But as doctors first started to apply this checklist, they discovered something awkward. Almost everybody who is grieving, it turns out, matches the clinical criteria for depression. If you simply use the checklist, virtually anyone who has lost someone should be diagnosed as having a clear mental illness. This made many doctors and psychiatrists feel uncomfortable. So the authors of the DSM invented a loophole, which became known as the grief exception. They said that you are allowed to show the symptoms of depression and not be considered mentally ill in one circumstance and one circumstance only—if you have recently suffered the loss of somebody close to you.

This exception is something that puts into question the whole reasoning behind a diagnosis of depression:

Why is a death the only event that can happen in life where depression is a reasonable response? Why not if your husband has left you after thirty years of marriage? Why not if you are trapped for the next thirty years in a meaningless job you hate? Why not if you have ended up homeless and you are living under a bridge? If it's reasonable in one set of circumstances, could there also be other circumstances where it is also reasonable?

On an unhealthy environment (the whole sum of experiences, i.e. day to day life) as cause for depression

George and Tirril had discovered people living in poverty were more likely to become depressed—but the data showed it was too crude to say the poverty caused the depression. No: something more subtle was happening. People in poverty were more likely to become depressed because on average they faced more long-term stress, and because more negative life events happened to them, and because they had fewer stabilizers.

But the underlying lessons were true for everyone, rich, middle-class, or poor. We all lose some hope when we're subjected to severe stress, or when something horrible happens to us, but if the stress or the bad events are sustained over a long period, what you get is the generalization of hopelessness, Tirril told me. It spreads over your whole life,16 like an oil slick, and you begin to want to give up.

These findings soon ended up as a key part of the basis for psychiatric training in many parts of the Western world. Most mainstream training courses began to teach that forms of mental distress such as depression and anxiety have three kinds of cause: biological, psychological, and social. They are all real. This is known as the bio-psycho-social model. It's simple. All three sets of factors are relevant, and to understand a person's depression and anxiety, you need to look at them all.

Causes for depression

1. Lack of meaningful work

Between 2011 and 2012, the polling company Gallup conducted the most detailed study ever carried out of how people across the world feel about their work. They studied millions of workers across 142 countries.

The results summarized:

  • 13 percent say they are engaged in their jobs (happy)
  • 63 percent say they are not engaged (sleepwalking though the workday)
  • 24 percent are actively disengaged (hate work)

Most people in most places are spending a large part of their awake time (a majority in many cases) doing something they don't find particularly engaging (with a fairly large proportion actively hating what they're doing). It's not crazy to hypothesize then that this might play a part in feelings of depression.

On lack of autonomy and work-reward balance

What Michael found when he did this was even more striking than the first results. It's worth spelling it out. If you worked in the civil service and you had a higher degree of control over your work, you were a lot less likely to become depressed or develop severe emotional distress than people working at the same pay level, with the same status, in the same office, as people with a lower degree of control over their work.

During the Whitehall studies, Michael had discovered one other factor that turns work into a generator of depression—and he could see it here, too. If these tax inspectors worked really hard and gave it their best, nobody noticed. And if they did a lousy job, nobody noticed either. Despair often happens, he had learned, when there is a lack of balance between efforts and rewards. […]

So Michael explained to the tax office bosses that a lack of control and a lack of balance between efforts and rewards were causing such severe depression that it was leading their staff to suicide.

2. Disconnection from other people

An experiment where over the course of two days the participants were asked to write down how lonely or connected they felt 9 times a day throughout the course of day one, and to spit in a tube throughout the course of day two.

When John and his colleagues added up the data, they were startled. Feeling lonely, it turned out, caused your cortisol levels to absolutely soar—as much as some of the most disturbing things that can ever happen to you. Becoming acutely lonely, the experiment found, was as stressful as experiencing a physical attack. It's worth repeating. Being deeply lonely seemed to cause as much stress as being punched by a stranger.

In another experiment people spent a day and a night in a lab. A psychiatrist was brought in to hypnotize participants in two different ways. One groups was led to remember moments where they felt really connected to other people, while the other group was made to remember moments where they felt lonely. Personality tests given before and after measured various psychological traits.

What John's experiment found was later regarded as a key turning point in the field. The people who had been triggered to feel lonely became radically more depressed, and the people who had been triggered to feel connected became radically less depressed. The stunning thing was that loneliness is not merely the result of depression, he told me. Indeed—it leads to depression.

Another study followed a group of people over multiple years, getting them in a lab once a year for physical and psychological evaluations. What the study found was the loneliness and isolation preceded depressive symptoms.

And the effect was really big. Picture the range of loneliness in our culture as a straight line. At one end, you are 0 percent lonely. At the other end, you are 100 percent lonely. If you moved from being in the middle—50 percent—to being at 65 percent, your chances of developing depressive symptoms increased eight times. The fact he has discovered this through two very different kinds of study—and a great deal more research he has done—led John to a key conclusion, one that has been gathering in scientific support: loneliness, he concluded, is causing a significant amount of the depression and anxiety in our society.

You can be surrounded by people and still be alone

Loneliness isn't the physical absence of other people, he said—it's the sense that you're not sharing anything that matters with anyone else. If you have lots of people around you—perhaps even a husband or wife, or a family, or a busy workplace—but you don't share anything that matters with them, then you'll still be lonely. To end loneliness, you need to have a sense of mutual aid and protection, John figured out, with at least one other person, and ideally many more.

3. Lack of meaningful values

Materialistic people are less happy

Tim's first tentative piece of research was to give this survey to 316 students. When the results came back4 and were all calculated out, Tim was struck by the results: materialistic people, who think happiness comes from accumulating stuff and a superior status, had much higher levels of depression and anxiety.

Was this something that happened only with young people? To find out, Tim measured one hundred citizens of Rochester in upstate New York, who came from a range of age groups and economic backgrounds. The result was the same.

Intrinsically motivated goals bring happiness, extrinsic ones do not

People who achieved their extrinsic goals didn't experience any increase in day-to-day happiness—none. They spent a huge amount of energy chasing these goals, but when they fulfilled them, they felt the same as they had at the start. Your promotion? Your fancy car? The new iPhone? The expensive necklace? They won't improve your happiness even one inch.

But people who achieved their intrinsic goals did become significantly happier, and less depressed and anxious. You could track the movement. As they worked at it and felt they became (for example) a better friend—not because they wanted anything out of it but because they felt it was a good thing to do—they became more satisfied with life. Being a better dad? Dancing for the sheer joy of it? Helping another person, just because it's the right thing to do? They do significantly boost your happiness

Twenty-two different studies have, in the years since, found that the more materialistic and extrinsically motivated you become, the more depressed you will be. Twelve different studies found that the more materialistic and extrinsically motivated you become, the more anxious you will be

4. Childhood trauma

The Adverse Childhood Experiences study was a questionnaire given to 17k people that asked about ten different categories of terrible things that can happen to you as a child (sexual abuse, emotional abuse, etc). It then followed up that line of questioning with a detailed medical questionnaire, testing for various things that could be going wrong with you - obesity, addiction, and of course, depression.

When the data came in the results were quite clear:

It turned out that for every category of traumatic experience you went through as a kid, you were radically more likely to become depressed as an adult.

Causality was inferred as there was a direct relation between how much trauma was suffered as a child vs how great the risk of depression, anxiety or suicide was. The greater the trauma, the greater the risk.

Curiously, it turned out emotional abuse was more likely to cause depression than any other kind of trauma—even sexual molestation. Being treated cruelly by your parents was the biggest driver of depression, out of all these categories.

5. Lack of status and respect

Stress and status among baboons and their cousins

It turned out—when his blood samples were tested—that when there is a war on for the position of alpha male, the most stressed baboons are the ones at the top. But the vast majority of the time, the lower you are in the hierarchy, the more stressed you are; and the baboons at the very bottom of the pile, like Job, are stressed constantly.

A few years after Robert's initial breakthrough, it was discovered that depressed humans are flooded with the very same stress hormone that you find in low-ranking male baboons. As Robert investigated these questions further,13 he discovered even more: you get, he explains, the same constellation of changes in the brain and pituitary and adrenal glands … [as in] depressed humans, too.

Inequality and depression

When they were finally able to plot the data on a graph, they were startled by how close the relationship was. The more unequal your society, the more prevalent all forms of mental illness are. Other social scientists then broke this down to look at depression specifically16—and found the higher the inequality, the higher the depression. This is true if you compare different countries,17 and if you compare different states within the United States. It strongly suggested that something about inequality seems to be driving up depression and anxiety.

6. Disconnection from the natural world

People living in greener areas have consistently higher scores for mood, happiness, and lower scores for depression or anxiety. This is reproduced across many studies and the effect is equally strong when you control for various factors - people in cities with similar social connections, status, wealth, still show a difference in stress and despair when there is a difference in the amount of green space throughout their neighborhoods.

Talking a walk in nature improves mood and concentration. This effect is dramatically bigger for people who are depressed. Exercise is undeniably a net benefit for health, both physical and psychological, and it seems exercising in nature has the biggest combined impact on depression.

When scientists have compared people who run on treadmills in the gym with people who run in nature, they found that both see a reduction in depression—but it's higher for the people who run in nature

7. Disconnection from a hopeful or secure future

A study done on the suicide rates across The First Nations - Native American groups in Canada - found a direct link between the level of autonomy of each group and their respective suicide rates. Groups that had gained enough independence from the Canadian government and had enough autonomy where they could more realistically control their own futures had lower suicide rates than those that were still under the full control of the government.

It was, he concluded, the loss of the future that was driving the suicide rates up. A sense of a positive future protects you. If life is bad today, you can think—this hurts, but it won't hurt forever. But when it is taken away, it can feel like your pain will never go away.

Another study done on sick children, hospitalized for various mental illness, found a strong link between depressed children and their ability to reason about the future:

Both groups of kids were equally sick, and their distress levels were similar. Yet the anorexic kids could answer these questions normally, while the depressed kids couldn't. Almost unique to the suicidal group was a kind of across-the-board failure to be able to understand how a person could go on being the same individual, Michael told me. The very depressed kids could answer all sorts of other questions normally—but when it came to these questions about what they or anyone else would be in the future, they would look puzzled.

Similarity, a lack of certainty about one's own economic future can lead to depression, and with an economy that is less and less able to provide stability and any kind of certainty about the future, depression is more likely to show up than ever before.

First, this sense of precariousness started with people in the lowest-paying jobs. But ever since, it has been rising further and further up the chain. By now, many middle-class people are working from task to task, without any contract or security. We give it a fancy name: we call it being self-employed, or the gig economy—as if we're all Kanye playing Madison Square Garden. For most of us, a stable sense of the future is dissolving, and we are told to see it as a form of liberation.

8-9. The real role of genes and brain changes

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. And Avshalom discovered—as Professor Robert Sapolsky explains—that 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. (They didn't test for most of the other causes of depression I've been talking about here, such as loneliness, so we don't know if they also interact with genes in this way.)

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

There are other situations 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.

Reconnection - a different kind of antidepressant

The Cambodian cow antidepressant

Derek tried to explain it. Depression is, he said, a profound sense of sadness that you can't shake off. The Cambodians thought about this carefully and said, yes, we do have some people like that. They gave an example: a farmer whose left leg was blown off by a land mine, who came to the doctors for medical help and got fitted with a new limb but didn't recover. He felt constantly anxious about the future and was filled with despair.

They then explained that they didn't need these new-fangled antidepressants, because they already had antidepressants for people like this in Cambodia. Derek was intrigued, so he asked them to explain more.

When they realized this man was despondent, the doctors and his neighbors sat with him, and talked through his life and his troubles. They realized that even with his new artificial limb, his old job—working in the rice paddies—was just too difficult, and he was constantly stressed and in physical pain, and that was making him want to just stop living, and give up.

So they had an idea. They believed that he would be perfectly capable of being a dairy farmer, and that would involve less painful walking on his false leg and fewer disturbing memories. So they bought him a cow.

In the months and years that followed, his life changed. His depression—which had been profound—went away. You see, doctor, the cow was an analgesic, and antidepressant, they told Derek. To them, an antidepressant wasn't about changing your brain chemistry, an idea that seemed bizarre to their culture. It was about the community, together, empowering the depressed person to change his life.

A materialistic society can change

In our culture, Nathan was starting to believe, we end up on a materialistic autopilot. We are constantly bombarded with messages that we will feel better (and less stinky, and less disgustingly shaped, and less all-around worthless) only if we buy some specific product; and then buy something more; and buy again, and on and on, until finally your family buys your coffin.

For example, the city of São Paulo, in Brazil, was being slowly smothered by billboards. They covered every possible space—gaudy logos and brands dominated the skyline wherever you looked. It had made the city look ugly, and made people feel ugly, by telling them everywhere they looked that they had to consume.

So in 2007 the city's government took a bold step—they banned all outdoor advertising: everything. They called it the Clean City Law. As the signs were removed one by one, people began to see beautiful old buildings that had long been hidden. The constant ego-irritation of being told to spend was taken away, and was replaced with works of public art. Some 70 percent of the city's residents say the change has made it a better place

Meditation and psychedelics

The largest scientific study of using meditation as a treatment for depression found something really interesting. It turned out that depressed people were significantly more likely to recover from depression if they went into an eight-week meditation training program than people in a control group who didn't. Some 58 percent of the control group became depressed again,1 while only 38 percent of the newly trained meditators did—a huge gap. Other studies have found that meditation is similarly helpful for people with anxiety. One different study honed this effect a little and found that meditation works particularly well2 for people who've developed depression as a result of abusive childhoods—they have a 10 percent higher improvement rate than others.

But what both deep meditation and psychedelic experiences teach us is the ability to see how much of that self—that ego—is constructed. Mark could suddenly see that his social anxiety had been a way of protecting himself—but he didn't need it any more. My friend Rachel could see that her envy was a way of protecting herself from sadness—and meditation enabled her to see she didn't have to be that way: she could protect herself with positivity and love instead.

Both of these processes, Roland told me, create a whole new relationship with mind. Your ego is part of you. It's not the whole of you. By having moments when your ego is—as he puts it—dissolved and merged into the greater whole, into the lake of humanity that Mark saw in his vision, you can see beyond your ego. You gain a radically different sense of perspective on yourself. As Fred put it to me, these experiences teach you that you don't have to be controlled by your concept of yourself.

Overcoming childhood trauma

What this suggests is it's not just the childhood trauma in itself that causes these problems, including depression and anxiety—it's hiding away the childhood trauma. It's not telling anyone because you're ashamed. When you lock it away in your mind, it festers, and the sense of shame grows. As a doctor, Vincent can't (alas) invent time machines to go back and prevent the abuse. But he can help his patients to stop hiding, and to stop feeling ashamed.


You aren't a machine with broken parts. You are an animal whose needs are not being met. You need to have a community. You need to have meaningful values, not the junk values you've been pumped full of all your life, telling you happiness comes through money and buying objects. You need to have meaningful work. You need the natural world. You need to feel you are respected. You need a secure future. You need connections to all these things. You need to release any shame you might feel for having been mistreated.

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