تدريب Shadowing: Stanford's Sapolsky On Depression in U.S. (Full Lecture) - تعلم التحدث بالإنجليزية عبر الفيديو

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Stanford University.
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Okay, there are all sorts of interesting diseases out there, and lots of them are quite exotic.
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You've got elephant lance syndrome, and you've got progeria, which is a disease when you basically die of old age when you're about 10 years old,
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and then you've got cannibals eating brains and getting prion diseases.
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And those are very exciting, and they're great and great junior high school papers about disease and such.
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Oh, no. OK, come up to the front, please.
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See, a couple more seats.
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There's a fan back there that's actually in the middle of the middle.
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So there are all sorts of these great made -for -TV UV diseases out there.
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But when you want to come to, say, basic meat and potatoes of human medical misery, there is nothing out there like depression.
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Depression is absolutely crippling.
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Depression is incredibly pervasive and thus important to talk about.
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I'll make the argument here today, a number of things, but one critical thing being that basically depression is like the worst disease you can get.
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And I'll make the argument for that in a bit.
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It is devastating.
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It is wildly common.
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Current estimates are 15 % of us in this room will have a major depression at some point
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or other in our lives.
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So that is not good.
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What is also clear is it is worldwide.
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Currently, World Health Organization says depression is the number four cause of disability on this planet.
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And by the year 2025, it's going to be number two after obesity, diabetes -related disorders.
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So it is bad news and it is becoming more common.
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Okay, so what I'm going to talk about today are seemingly two very, very different topics and tie them together at the end.
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And what the main point is is if you live inside only one of those topics, you're not to understand this disease at all.
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First topic being, what does biology have to do with depression?
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Second topic being, what does psychology have to do with it?
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OK, so starting off, first giving a sense of symptoms.
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And right off the bat, we've got a somatic problem, which is we all use the word depression in an everyday sense.
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You get some bad news about something, you know, and replace the transmission in your car.
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Somebody disappoints you enormously.
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And you feel bummed.
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You feel depressed.
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You were down for a few days.
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That's not the version of depression I'll be talking about.
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Next version, you do have some sort of large legitimate loss, setback, whatever, losing a job, unemployment, death of a loved one.
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And you are extremely impaired by a sense of malaise for weeks afterward.
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And then you come out the other end.
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That's sort of what I'll be talking about.
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But even more so what I'll focus on is the subset of individuals who, when something like that occurs, falls into this depressive state.
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And weeks and months later, they still have not come out the other end.
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Terminology, the everyday depression that we all have now and then, that sort of version.
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The second one, the something awful happens, and you feel terrible for a while, and then come out the other end, a reactive depression.
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The third version, where you are flattened by it for long periods afterward, a major depression.
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And what you also see with people with major depression after a while is it doesn't take something awful externally
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to trigger one of those again.
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OK, so what are the symptoms about?
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If I had to define major depression in one sentence,
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I would say it's a biochemical disorder with a genetic component and early experience influences where somebody can't appreciate sunsets.
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And that's what this disease is about.
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And when you think about it, that is a very sad thing.
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You look at some of our major diseases, somebody with cancer, somebody crippled by heart disease, and you see the most unlikely things out there.
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You see somebody saying, well, obviously, I'm not glad I'm dying of cancer.
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But without this disease, I never would have realized the importance of friends.
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I never would have reconciled with my family members.
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I never would have found my god on a completely weird level.
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I'm almost glad this has happened to me.
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Humans have this astonishing capacity to derive pleasure out of the most unlikely domains.
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What could possibly be worse than the disease whose defining symptom is the inability to feel pleasure?
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Thus, at the top of the list, anhedonia.
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Hedonism, the pursuit of pleasure and hedonia, the inability to feel pleasure, that is what a depression is about.
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And you get someone who has just had some enormous, good luck, a long -sought relationship, works out well, whatever, and they feel nothing.
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An inability to feel pleasure, way at the top of the list.
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What else?
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Grief, guilt, and that's where we've got the semantic problem again, which is the everyday sort of depression.
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Something happens, bumps us out, and by definition, we are feeling some version of grief.
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Often we start obsessing at that point over some miserable thing we did to somebody 12 years ago and sort of despair.
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And that when you're talking about major depression, the grief and the guilt can be so severe that it actually takes on a delusional quality.
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OK, not delusional in the sense of the schizophrenic with delusions, hearing voices, thought disorder, but a certain style of extreme depression.
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Let me give you an example.
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You have a late middle -aged guy, perfectly healthy, and suddenly out of nowhere he has a major heart attack.
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He's lying there in the hospital and the reality is he's going to recover.
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He's going to have to make some changes in his lifestyle, but he's going to recover.
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He instead falls into a major depression.
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This has transformed his sense of who he is.
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Suddenly he's an old man.
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Suddenly there's all these things he can't do.
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He falls into a major depression yet he's recovering.
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Every day his family is in there saying, look you're just depressed, you're getting stronger.
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The doctors are saying you're getting stronger, you're just depressed.
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It happens the hospital is circular, it has a corridor that forms a circle in it.
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And one day the family is in there saying you're getting stronger,
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look the nurses said yesterday you did one loop around the hospital and today you did two loops, you're getting better, you're getting stronger.
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And the person says, no, no, no, no, you don't understand.
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They're doing some construction.
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Last night, they closed down the outer corridor, and they opened up a new little one to the two versions of this one.
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Two loops there are shorter than the large one.
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I'm getting weaker, I'm getting weaker, I'm getting done.
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This is like someone expecting to believe that last night there were like beavers digging through walls there, making this new.
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This was the father of an acquaintance of mine, a structural engineer.
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This is what a structural engineer looks like
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when they're delusional to the point of saying that this is a world in which everything is inevitably getting worse.
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Depression built around that.
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Next, of course, one of the most dramatic and one of the most awful symptoms of depression, self -injury.
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Depression depresses mutilating themselves at a high rate.
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And of course, most notoriously, suicide, risks of suicide.
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And that is absolutely tragic.
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And teenagers, early adults, that, along with accidents, is the leading cause of death.
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Major bad news.
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Another set of symptoms that wind up being important, something called psychomotor retardation.
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Everything is exhausting.
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It's exhausting to do stuff.
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It's exhausting to think stuff.
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You were there, and you can't do the laundry because where's the basket? and you've got to find change for the machine,
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and you've got to go get detergent, and just it's too much.
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Everything is too much, and you fall into this paralyzed state.
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Something very interesting in that regard.
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You get someone who is severely depressed, like to the point of hospitalization, and when they are absolutely crippled with psychomotor retardation,
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that's not when you worry about suicide.
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This is someone who's having enough trouble getting out of bed and getting dressed each day,
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They're not going to figure out how to shred the hospital mattress and make a noose out of it.
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Where you've got your problems is when somebody begins to get better.
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From a severe depression, when they're starting to come out,
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that's where the psychomotor retarination relieves enough that suddenly they've got the energy to do something catastrophic.
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That's when people are on suicide watches, when you have clinicians who are oriented well.
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Next, something really interesting.
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And in lots of ways, the single point I want to hammer in here over
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and over and over is something that people with depression constantly battle with.
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Back to semantics.
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We all get depressed.
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Bad stuff happens to us.
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We all get depressed.
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We feel lousy.
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We feel withdrawn.
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We feel sort of a sense of grief, and we're not taking much pleasure, and we withdraw.
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And then we get better.
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We cope.
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We heal.
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We deal with things in life what's the deal with you that you can't do that?
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And there is this lurking sense given that all of us have periods of being depressed and come out the other end.
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When you look at people who instead go down and stay down there to this crippling extent,
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there's always this little voice between the lines there of, come on, pull yourself together.
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We all deal with this sort of thing.
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I will make the argument throughout here that depression is as real of a biological disorder as is juvenile diabetes.
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And you don't sit down a diabetic and say, oh, come on.
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What's with this insulin stuff?
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Stop bathing yourself.
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You don't put it together.
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You will see this is just as much of a biological disorder.
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Part of what makes that clear are a bunch of symptoms called vegetative symptoms.
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The bodies of major depressors work differently.
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First set of symptoms.
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No surprise, lots of people have trouble sleeping when they're having every day off the rack depression.
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There's a certain pattern with people with major depression.
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What would you think?
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You know, you're depressed, you have trouble falling asleep, toss and turn.
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That's not what you see with a major depressive.
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Instead, you wake up early.
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You wake up four in the morning, five in the morning, you're exhausted, but you're not going to sleep early morning wakening.
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You wind end up in an emergency room somewhere deeply depressed.
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And the clinician there better ask you at some point, how's your sleep been?
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Do you tend to wake up early in the day?
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Early morning wakening, classic sign.
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Additional thing, while sleeping, sleep is not this monolithic process.
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There's all these different stages of sleep, slow wave sleep, deep sleep, REM sleep, all of that.
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There's a structure and architecture to how we sleep, sort of 90 -minute cycles as you go through the different phases,
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you look at the brain of somebody with depression while they're sleeping.
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And these different phases are completely disordered.
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The whole structure of sleep goes down the tubes.
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Look at somebody when they're sound asleep, and their brain sleeps differently.
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This is not, oh, come on, stop babying yourself.
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This screams biology.
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More versions of it.
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Most of us, what we do
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when we're feeling kind of down is we eat more out of this general belief that when you feel unloved, carbohydrates make you feel better.
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And bizarrely, there's actually a brain chemistry of it, of carbohydrates decreased stress hormone release.
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So for most of us, you're feeling bummed out about things.
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You eat more.
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That's not what you see in major depression.
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Decreased appetite.
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Another thing you see is activation of the stress response.
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A class of stress hormones are highly elevated in people with major depression,
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you also have over activation of something that's called the sympathetic nervous system, adrenaline.
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Over activity of these components of stress response, and that's really important.
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Because you look at someone with a major depression who's just mired in the psychomotor retardation stuff,
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and there's this temptation to start thinking about them as some sort of like sea sponge, some invertebrate thing, where you're just so wiped out,
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you can't even get out of bed.
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It is just debilitating in that sense.
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That's not what's going on during depression.
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What you have instead is somebody whose body is blasting through their over -activated stress response,
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this enormous battle, all of it going on internally.
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And the fact that you see changes like these tell you this is not, oh, just so wiped out you can't even activate.
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This is someone whose body is having a massive stress response 24 -7.
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There's a huge battle going on, and it's all internally increased metabolic rate, increased muscle tone, all of this, again, screaming biology.
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The final thing that says tons of biology is lots of people with major depression have rhythmic patterns to the depression.
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You will get somebody where they will fall into a depression where they will have two months of extreme severe symptoms,
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seems debilitating, come out the other end, and a year and a half later,
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the exact same pattern, a year and a half later, exact same thing.
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You have some people who only get their depressions during the winter, something known as seasonal affective disorders, SADs.
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And this is someone where something horrible happens to them in June, and they feel sort of sad for a couple of weeks,
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and they come out the other end, and nothing happens in January, and they fall into a depression,
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and they're hospitalized for a month and a half, just like every January for the last 10 years.
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And you see that, and that is all about biological clocks that are out of whack there.
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It's biology.
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This is not, oh, come on, pull it together.
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OK, so hopefully what that begins to introduce is the notion, amid all these debilitating symptoms, these are ones that are about biology.
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These are bodies working differently.
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So starting to focus in more on the biology of it.
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What's going on in the brain in major depression?
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What I'll start off with is the chemistry of it.
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OK, what we've got here, do not panic if you are not familiar with this
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and have not wanted to think about science since high school sort of thing.
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You've got two brain cells.
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You've got two neurons.
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The way they talk to each other, they don't actually touch each other.
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In order for one neuron to send a message to another one,
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it needs to release a chemical messenger that goes floating over here and does something or other to this neuron.
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Chemical messenger called a neurotransmitter.
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And here we have a case of this.
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And by law, all neurons go from left to right.
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So this is a cell that continues down this way.
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It's all excited.
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It's trying to pass on some news to this neuron.
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There's a space in between called a synapse.
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And what this one is doing, because it's all excited, it has these little water balloons filled with neurotransmitters.
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Excitation signal comes along, dumps the neurotransmitters, They go floating across the synapse, bind to a receptor there.
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And then suddenly, something changes in this neuron.
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That's how neurons talk to each other.
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How many different types of neurotransmitters there are?
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Probably hundreds.
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And what will be pertinent here is, in depression, there's just a handful of them that seem to be implicated.
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First neurotransmitter, something called norepinephrine.
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Norepinephrine first got implicated in depression in the early 50s, in the early 60s, rather.
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What was the evidence?
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Around that time, the first generation of antidepressant drugs had been developed, something called MAO inhibitors.
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What do they do?
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OK, so you got your neurotransmitters released.
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The zysineuron's excited.
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What do you have to do?
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It comes out.
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It does its thing with receptors.
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And then you have to clean up after yourself.
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You've dumped all the stuff in the synapse.
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What do you do then?
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You've got two options.
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You can take the neurotransmitter, and you can be green in your orientation.
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You can recycle it.
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You can take it back up in here and stick it back into one of these.
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You can do this recycling business.
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Or you could be terrible and carbon footprint.
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You can throw out your neurotransmitter.
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There's like enzymes sitting around here that break it up and flush it down the toilet.
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What's the toilet?
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Out into your cerebral spinal fluid, your bloodstream, your urine, whatever.
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So either recycling or degrade this stuff.
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So what do these MAO inhibitors do?
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They inhibit the activity of this enzyme that breaks down norepinephrine.
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OK, so what's the logic there?
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So you inhibit the activity of this enzyme.
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You don't break down norepinephrine.
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So it's just floating around there.
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And for lack of anything else to do, it hits the receptor a second time, and a third time, and a gazillionth time.
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And suddenly, somebody's depression goes away.
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What's your theory have to be at that point?
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Ooh, I bet there wasn't enough norepinephrine coming out.
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You find a means to increase the signaling.
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Somebody gets better.
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And you now hypothesize there's a problem with too little norepinephrine.
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By the late 60s, another class of antidepressants came in, the tricyclic antidepressants.
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What do they do?
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Essentially the same exact thing.
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What they do is they gum up this pump that recycles the stuff.
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Neuropenephrine doesn't get removed from the synapse, has nothing else to do, hits the receptor second, third, tenth time, person feels better.
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Ooh, I think the problem in my theory is too little neuropenephrine coming out.
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Thus, the neuropenephrine hypothesis.
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More evidence for it, there are classes of drugs that will decrease your neuropenephrine release.
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Why would you want to do that?
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In some parts of the body, an excess of norepinephrine has something to do with high blood pressure.
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So you take a class of drugs, something called reserpine, and what it does is it disintegrates these things.
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And thus, you don't dump as much norepinephrine.
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Major side effect in lowering somebody's blood pressure that way is they fall into a depression.
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So you take a depressed person, you find a way of boosting up their norepinephrine signaling, they feel better.
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You take a normal person, you drive down their norepinephrine signaling, they get depressed, there's got to be a problem here of too little norepinephrine.
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So that's incredibly convincing.
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So at this point, what you've got to say is, OK, great.
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That's convincing.
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That's irrefutable.
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What does norepinephrine do?
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And people figured it out in the 50s, and it's got something to do with this.
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Take a rat and take a certain part of the brain.
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You put an electrode down in there where you can stimulate the neurons.
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You can force them to talk to each other when otherwise they have nothing to say, stimulate this pathway.
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And what you do is you make a rat unbelievably happy.
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OK, so of course the question is, how do you tell when a rat's unbelievably happy?
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What you do is you make it work in order to get stimulated there.
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It presses a lever, and it presses a lever 25 times, and it gets a little buzz there, and it does another time.
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And rats will work themselves to death to get stimulated in this area.
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It is better than food.
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It is better than sex.
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If they're addicted to a drug and going through withdrawal, it is better than the drug.
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And what you see is this mediates pure pleasure.
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And this was called the pleasure pathway in the 1950s.
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So of course, you look at it.
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And then what you have to then say is, ooh, do we have the same pathway?
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Can I get a new one?
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Can I get a second one?
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Shortly after that, people went looking and saw the exact same thing in humans.
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And this would be during neurosurgery, sort of classical neurosurgical techniques.
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You don't anesthetize the person.
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The brain doesn't feel pain.
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Once you've anesthetized the skin and the skull, you get through there.
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And you can actually keep somebody awake during surgery.
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And they used to need to do that, because you put on your little needle down one part of the brain,
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and the person flaps their arm, and another part, and they say the Pledge of Allegiance.
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And then you look at your little road map, and it says, OK, go three neurons and make a left.
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People had to do that.
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So it was around the early 60s that people started stimulating the same area in the human brain.
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And it is unbelievable what you got.
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There were transcripts of some of these.
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And you read it, and the person is going on.
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They're seeing stuff like, oh, that's great.
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That's great.
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That's kind of like sex.
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But you know when you have this itch, and finally you get to scratch it?
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And you're like, oh, it's like getting back to bed.
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And you know, remember how, like in the fall, you'd go out and play in the weeds,
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and mom would call you in and she made cookies and then you get into your jammies with your feet on them.
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They just go on.
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Where can you sign up and have this happen?
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The same exact sort of theme as in a rap.
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And it was around that time that people discovered that in this pathway it uses norepinephrine.
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Aha!
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So if you've got a shortage of norepinephrine in that part of the brain, what have you just explained?
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That's the loss of pleasure.
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Great, utterly convincing.
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Here's all the reasons why you shouldn't be convinced.
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Problems began to emerge.
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First problem was, there's something weird with the time course.
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You throw in any of the drugs I just talked about, and norepinephrine signaling is changing within like an hour.
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You put a depressed person on those drugs, and they don't get better for a couple of weeks.
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Something isn't working there.
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So that was mysterious.
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Next problem was, it turned out, norepinephrine is useful in this pathway, another neurotransmitter turned out to be even more important, neurotransmitter called dopamine.
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Dopamine cocaine works on dopamine systems.
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So suddenly, neuroconnection is just a minor player in this pleasure pathway stuff.
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But the biggest problem came in the late 80s with the introduction of Prozac.
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Prozac, which is an SSRI, a selective serotonin reuptake inhibitor, what that does is we're
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We're on a completely different neurotransmitter system.
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This neurotransmitter called serotonin.
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What that drug does is it does the same deal.
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It stops the reuptake, increased serotonin signaling.
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And then once your hypothesis, ooh, you give somebody a Prozac SSRI, they feel better, I bet you there was too little serotonin.
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So it was during this period where there was just endless tragic drive -by shootings of norepinephrine people by the serotonin crowd.
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And there was a huge, huge controversy.
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And of course, like
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Miller the road liberals, and why can't we all get along, would start suggesting that, oh, maybe it's got something to do with norepinephrine,
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and serotonin, and dopamine, and everybody hold hands, and oh my gosh, and that's absolutely what's going on.
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The best evidence at this point to be insanely simplistic is that dopamine has something to do with the anhedonia, an absence of dopamine.
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The absence of norepinephrine has something to do with the psychomotor retardation.
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The absence of serotonin is this obsessive sense of grief.
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And interestingly, supporting that notion is you can have an obsessive sense of something else.
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You can have an obsessive need to keep your utensils perfectly symmetrical and obsessively wash your hands eight hours a day.
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Obsessive compulsive disorder, that's helped by SSRIs like Prozac as well.
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Whatever it is you are just perseverating over like mad, getting increasing serotonin signaling can help.
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So you've got at least three different neurotransmitters relevant to the pleasure, the psychomotor retardation, all of this,
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all sorts of other leads floating around the field.
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There's a neurotransmitter called substance P.
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And what substance P is about is pain.
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Like, poke your finger and your spinal cord, or there's neurons there releasing substance P talking to each other.
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It's about pain.
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It's about chronic pain syndromes.
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It's about whole body burns.
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Everybody knew this.
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And then it was discovered that if you get a drug that decreases substance P signaling, sometimes depressives get better.
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What does that suggest?
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It is not just a metaphor of depression as psychic pain.
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Your body is using the same brain chemistry to feel this sort of psychic pain of depression as just telling you,
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ooh, I just stubbed my toe.
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Interesting similarities there.
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OK, so we got something about the neurochemistry.
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How about the neuroanatomy, the structure of the brain?
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And what you've got here is this is the human brain.
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This is exactly what it looks like.
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It comes in three colors.
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And this was this formulation that came out during the 40s called the triune brain concept, which wanted to be really, really spiratory.
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Down here at the bottom, you've got the really boring nuts and bolts part of the brain.
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And this was termed.
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This is the reptilian part of the brain.
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Take a lizard, and it's basically the exact same stuff down there.
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What does this part of the brain do, like regulatory, boring things?
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It measures your blood glucose levels, or if your blood pressure is dropped, it sends out a signal to tighten up your blood vessels.
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Just total boring plumbing -type issues.
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Sitting on top of it is a much more interesting brain region called the limbic system.
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Limbic system is about emotion.
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You don't see a big limbic system until you get to mammals.
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Lizards are not famous for their emotional lives.
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The limbic system is much more about emotive stuff.
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Fear and lust and anger and rage and poignance and God knows what.
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What you've got there are all sorts of ways where the limbic system talks to this part of the brain.
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And what it does is, rather than you being hemorrhaged, ooh, park this brain, your body getting cold,
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whatever, hurt, you're some elk and there's some scary other elk there that's got you all upset, and you start secreting stress hormones.
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That's your limbic system saying, ooh, I don't like the smell of that by talking down there.
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All sorts of means by which your emotional part of the brain can talk to stuff down here.
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Then you've got the really interesting area.
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Up on top, the cortex.
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Cortex, all sorts of creatures out there have cortexes we got more than anybody.
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It is this hugely expanded area.
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And primates, we proportionally have the biggest one out there.
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What does cortex do?
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It makes you do your taxes.
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And it does like processing visual information and tells you, aha, that's punk rock, and that's not Beethoven.
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And then all sorts of sensory stuff associated cortex things.
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But then there's an interesting part of the cortex that's very relevant to all of this.
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OK, suppose you finish the lecture.
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You go outside.
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Unexpectedly, you are gored by an elephant.
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What are you going to do?
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You are going to activate your stress response.
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You may feel a sense of grief at that point.
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You may kind of hunker down at that point, a little psychomotor retardation.
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Appetite, there goes the dinner arrangements.
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Sex may not be the most appealing thing under
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that context you are having a stress response in response to the sort of insult
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that this part of the brain is thinking about.
415
So what's a depression?
416
You sit there and you think about kids in refugee camps, you think about the inevitable mortality of your loved ones,
417
you think about whatever, and suddenly your body does the exact same thing as if you were gored by an elephant.
418
And what's going on there is you get the feelings, the abstract sort of depressive stuff there,
419
and this part of the brain is able to make the rest of the brain go along with it as
420
if this was an elephant goring you.
421
On a certain totally simplistic level, what depression is about is the cortex whispering in the ear of the rest of the brain saying
422
this is as real as you were just physically assaulted by some sort of predator, whatever, and you turn on the exact same thing.
423
On a very simplistic level, what a depression is is a cortex having too many sad thoughts
424
and getting the rest of the brain to go along with it.
425
OK, so that's how you think about depression, which is insanely simplistic.
426
You can come up with an insanely simplistic treatment for depression,
427
which is get yourself a pair of scissors and separate that part of the brain for the rest of it.
428
And you're home free.
429
Oh, yeah, right.
430
Well, that's certainly an advance in medicine.
431
That is a medical procedure.
432
It is called a cingulotomy.
433
The part of the cortex called the anterior cingulate, a cingulotomy, or a cingulum bundle cut.
434
And what you do is you sever this pathway.
435
And people get less depressed at that point.
436
OK, when does this happen?
437
This is someone where every type of medication and every type of therapy and electroshock interventions, all of that has been tried.
438
And every combination, and they're still on the backboard of the state hospital slashing their wrists every three months.
439
That's when people try this.
440
And the amazing thing of this desperate measure is people get less depressed at this point.
441
OK, so at that point, you may want to look at that and say,
442
well, anything else about these people when you've gone through there and just snipped away?
443
Mind you, this is not a frontal lobotic.
444
Frontal lobotic is doing something very undefined there but instead you're disconnecting here.
445
What else is up with somebody when you've just disconnected part of their cortex from the rest of the brain?
446
Ooh, insofar as the cortex can come up with abstractly sad thoughts
447
and get the rest of the brain to go along with it,
448
maybe the cortex also comes up with abstractly pleasurable thoughts and gets the rest of the brain.
449
Have you just wiped out somebody's ability to have abstract pleasure?
450
Absolutely.
451
So suddenly you are off and running with a great philosophy term paper, ooh, it's important that we have pain in order to have pleasure.
452
This is nonsense.
453
You get someone who's a candidate for this procedure back in the state hospital
454
there with the wrists scarred over at this is not somebody feeling a whole lot of abstract pleasure anyway.
455
So what does this tell us?
456
You come up with some ridiculously simplistic explanation that,
457
ooh, you make it impossible for this sad part of the brain to whisper sad thoughts to the rest of the brain.
458
The best people in the field thinking about this can't come up with anything a lot more sophisticated than that.
459
So that tells you something about the brain structure with depression.
460
Final bit of biology here, hormones.
461
What do hormones have to do with it?
462
One very important domain of hormones.
463
You take somebody, and they're having problems with a class of hormones, thyroid hormones.
464
What thyroid hormones are about is maintaining your metabolism, keeping your body warm enough, all that sort of stuff.
465
If you have a severe shortage of thyroid hormone, lots of things happen, including you fall into a major depression.
466
Hypothyroidism is associated with major depression.
467
There's an autoimmune disease called Hashimoto's disease, which involves problems with secretive thyroid hormone, and that's a basic feature of it.
468
And somebody comes in, and you diagnose it, and you give them normal levels of thyroid hormone, and away goes their depression.
469
Lots of lessons with that.
470
First one is, best estimates are about 20 % of major depressions, are undiagnosed hypothyroid syndromes instead.
471
The next one that demonstrates is you better, when somebody is thinking about your psychiatric state, you better have somebody there who's thinking about your nutrition,
472
your hormone levels, your nothing about what's going on here is independent of the rest of the body.
473
So a big role for thyroid hormones.
474
Next domain of hormones being relevant, you take women.
475
You take women and they have a higher incidence of major depression than men do, approximately twice the rate.
476
In addition, women have their highest vulnerability to depression at certain points in their reproductive life histories.
477
After you've given birth, a postpartum depression, around the time of your period, around the time of menopause,
478
all of these scream biology.
479
So you look at why women have elevated rates of depression, and there's biology.
480
There's all sorts of other schools of thought that have gone into it.
481
There are ones having more kind of sociological framework.
482
Lack of control can cause depression in society after society.
483
Women traditionally have less control.
484
No wonder they fall into more depression.
485
There's another school that focuses on a certain style of emotional differences you see between the genders on the average,
486
women tend to ruminate more on emotionally upsetting things to focus in on them more.
487
And this sounds totally stereotypical.
488
And when you do the studies, there's overlaps between individuals.
489
But nonetheless, on the average,
490
what you see is these sorts of studies where you get someone after they've just had a fight with a close friend.
491
And what do women do when they give a choice of a whole bunch of activities?
492
They choose to fill out questionnaires about how they met their friend, what relationship is, does a friend have a good marriage, and all of that.
493
You do it to guys, and they fill out questionnaires about, like trivia questions about the Civil War.
494
Oh my god, they can't express their emotions.
495
They're impossible.
496
And of course, again, individual variation.
497
This is highly stereotyping.
498
On the average, though, women ruminate more on upsetting emotions than men do.
499
So that is solid science.
500
What is completely unsolid science is the speculation at that point that if you ruminate on bad feelings, you're more prone to a depression.
501
So that's a whole emotional regulation argument.
502
But you come back to that business of women are most at risk for depression in the two weeks after giving birth,
503
around period of their period is menopause, and that's all about hormones.
504
And by now, there's a huge literature having to do with the effects on all
505
that stuff over there of estrogen and progesterone and probably most importantly, the ratio of estrogen to progesterone,
506
and what's going on around giving birth, what's perimen, levels of this stuff is just shooting around all over the place,
507
and the sense is something goes out of whack with the ratios there,
508
and everything about estrogen to progesterone to the ratio can change the number of receptors for these neurotransmitters,
509
the extent to which you do this re -up to the pump.
510
Whatever depression is going to turn out to be on this nuts and bolts level, estrogen and progesterone can do something to it.
511
Final class of hormones that are relevant.
512
A class of hormones released during stress.
513
Okay, what's the most famous stress hormone?
514
Adrenaline.
515
Adrenaline is this vastly overrated hormone that I despise
516
because there's a much more important stress hormone out there to which I've devoted the last 30 years of my life.
517
A class of stress hormones called glucocorticoids.
518
They come out of your adrenal gland during stress.
519
The human version is hydrocortisone, also known as cortisone.
520
All sorts of other species out there.
521
You secrete these glucocorticoids when you are stressed.
522
You look at people with major depression, and about half of them have elevated levels of glucocorticoids through the roof.
523
There is something out of whack with the regulation of this stress hormone during depression.
524
What's that about?
525
That's back to people with depression are not invertebrates sitting here in their beds.
526
These are bodies undergoing massive stress responses.
527
There's a huge emotional battle going on, all of it inside their heads.
528
So elevated stress hormone levels.
529
What's very clear is you get exposed to a lot of glucocorticoids, and you're more at risk now for depression.
530
You can see this epidemiologically.
531
You get people, and statistically, before their first major depressive episode, something awful stressful occurs and that's where this happens
532
and this is the subset of people who stay down
533
there far longer have one of those first depressive episodes due to some stressful event
534
you come out the other side eventually
535
you were no more at risk for depression than anybody else along comes the second major stressor
536
and you fall into a depression come out the other end
537
no more at risk for anyone at any than anyone else for depression somewhere around the fourth or fifth stress -induced depression,
538
something happens and things start cycling on their own there
539
and you no longer need a major stressor to cause you to get depressed like that.
540
That's when the clocks are off and running.
541
That's the transition.
542
OK, so major stress can predispose you towards depression.
543
More evidence.
544
There's a disease called Cushing's disease, where people secrete boatloads of this glucocorticoid stuff.
545
People with Cushing's fall into depressions.
546
There's a whole bunch of diseases where people have to be treated with lots of glucocorticoids.
547
They fall into depression.
548
What are glucocorticoids doing?
549
A whole lot of them.
550
And your brain gets depleted of dopamine.
551
And you're right back in this domain that's probably neurochemistry, how do you get there?
552
OK, so what do we got at this point?
553
We got something about brain chemistry depression.
554
We got something about the structure of the brain.
555
We got something about hormones.
556
You are a card -carrying biological psychiatrist, and that's all you need to know about the subject.
557
And if that's all you know about the subject, you are going to be pitifully bad at making anybody get better.
558
Because all of this knowledge winds ends up being effective for treating maybe 30%, 40 % of depressives.
559
The vast majority of people, the antidepressant drugs, don't do a whole lot there.
560
All you got there is modern, cutting edge biology stuff, and that's not enough.
561
So what I'll transition to here is now talking about the psychology of depression, because you'd better have that piece of the story,
562
or else you're absolutely useless.
563
Starting off with, I make apologies here, but I actually have to say the name of Sigmund Freud.
564
Because he wants to be very relevant to depression.
565
Freud, back when, dealt with this puzzle of the difference between we all get depressed and come out the other end,
566
and the subset of people who crash.
567
The turn of the century Viennese term for people who come out the other side, mourning.
568
You mourn something and you recover.
569
Turn of the century Viennese term for major depression, melancholia.
570
And Freud, in this famous essay, said, why is it that a subset of us fall into it and don't count?
571
What's the difference between mourning and melancholia?
572
And he came up with a really interesting model.
573
Okay, according to Freud, you have mixed feelings and glibbalances about everybody you love out there.
574
You love them and you hate them and you resent them
575
and you yearn for them and you reject them and all that Freudian stuff.
576
So in this Freudian view, you have lost a loved one.
577
That can also be a loved concept, a loved goal, a loved thing.
578
You have lost a loved one.
579
What happens then is, in most people, you are able to focus on the love and the sense of loss.
580
You mourn, and you come out the other end.
581
In Freud's view, what melancholia is about is the subset of people who can't quit.
582
the negative feelings in the background, and instead you are awash in the love, and the hate, and the regret,
583
and the pain, and the delight, and all of that.
584
And what a depression is, is this wallowing, this melancholic loss in the ambivalencies you have about the lost loved one.
585
It explains tons.
586
No wonder you have the grief.
587
Lose somebody and go through the morning business, and only one thing is wrong.
588
You've lost this loved one.
589
You've lost somebody with melancholia, and two things have happened.
590
You've lost the loved one, and you have now lost the opportunity to ever make things better with them.
591
No wonder you have the guilt.
592
You're sitting there saying, thank God I'm finally done with this person.
593
They are never going to control my life.
594
How can I think such a thing like that?
595
Sudden, crippling guilt.
596
All sorts of other symptoms.
597
And out of this came this wonderful sound bite.
598
Depression is aggression turned inward, because you've got nobody else out there to have these arguments with.
599
This is the person who you have most loved, the most hated, and you've never said the things you needed to hear,
600
and pounding at the door to get them to finally be able to tell them.
601
And now you've lost that opportunity forever.
602
And all you can do is internalize all of that aggression turned inward.
603
No wonder you're not feeling a whole lot of pleasure.
604
No wonder you're secreting stress hormones.
605
No wonder you're not getting out of bed all that readily with the psychomotor retardation stuff.
606
This really powerful sound bite of aggression turned in.
607
That's great.
608
What isn't great is how in hell do you turn like Freudian ambivalent feelings into something about neurochemistry?
609
Or like, what do estrogen progesterone ratios have to do with like love -hate ratios?
610
It's great.
611
It feels very intuitive it, you can't do modern science on it, which is a problem with the best parts of world.
612
OK, so instead, you need to shift over to looking at experimental psychology and understanding what is the psychology of stress.
613
What is it that makes psychological stressors stressful?
614
And an enormous literature now shows that for the same external misery, you feel more stressed, you turn on stress response,
615
you have more risk for stress -related disease if you don't have outlets for the frustration caused by the stressor,
616
if you feel like you have no control over what's happening, you have no predictability as of when it's occurring,
617
and you don't have anybody's shoulder to cry on.
618
This is what psychological stress is about.
619
And what a depression is is pathological extremes of this.
620
You fall into the cognitive psychology soundbite of what a depression is.
621
It's learned helplessness.
622
It is learning to be helpless something bad happens to you you a rat getting some shocks now
623
and then you a human experiencing some loss
624
and the logical thing you should do is learn this is awful
625
when I'm in this situation there's not a damn thing I can do about it it's awful I feel terrible
626
but this is not the whole world
627
and what a major depression is about is you sit there
628
and you're that rat and in this setting you get uncontrollable shocks
629
but put you in another setting and just by hitting the a couple of times you avoid the shocks,
630
you don't bother doing it because you've learned to be helpless.
631
Just like a human depression.
632
What depression, what learned helplessness is, is taking a circumstance whereby any logic, again, you should be saying,
633
this is awful, but it is not the whole world.
634
And do this cognitive distortion and decide, this is indeed the entire world.
635
And I have no control.
636
I am always helpless.
637
I am always hopeless this is the psychology of what a depression is about.
638
At that point, you don't have a whole lot of trouble seeing how you wind up in here, stress, effects on some of the dopey,
639
all that sort of stuff.
640
OK, so we've got two extremely different viewpoints here as to what depression is about.
641
Modern, biological stuff, and this totally different world of psychology, loss, lack of control.
642
One version of it, one of the most reliable findings in the whole epidemiology of depression is lose a parent to death
643
when you are under 10 years of age, and for the rest of your life you are more at risk for a major depression.
644
This makes perfect sense.
645
What is a lot of what's going on during your first 10 years of life?
646
You were learning about cause and effect.
647
You were learning about, you're learning, is this a world out there where I have any sort of efficacy, we're in any sort of control,
648
and you have just learned in the most big time awful way, there are things you can't control and sometimes they are awful,
649
and what have you just learned, there's all sorts of reasons where one can be helpless,
650
and you're that much closer to this edge of this learned helplessness cliff for the rest of your life.
651
Extremely powerful model here of that.
652
So you've got all the biology stuff.
653
You've got this weird Freudian aggression turned inward, which just feels right.
654
But you can't do modern science on it.
655
You've got this whole world.
656
How do you begin to put this world and that world together?
657
And the critical link turns out to be stress.
658
Stress is the intersection of the two in a very interesting domain.
659
OK.
660
Depression is a genetic disorder.
661
What do I mean by that?
662
Depression has some degree of heritability.
663
Depression tends to run in families.
664
Depression runs more reliably as you look at closer and closer relatives, and you eventually look at identical twins.
665
And if one of them has depression, the other has a 50 % chance.
666
Full siblings who are not identical twins, 25 % chance.
667
Half sibling, about 8%.
668
Person off the street, about a 2%.
669
50 % chance when they share the identical genes, what does that do?
670
That tells you this is a disorder that has a genetic component.
671
What does that also tell you?
672
If we've got 50 % likelihood, if you've got all the genes in common, and you've got a 50 % chance of not getting the depression,
673
it tells you genes are important, but they're not more important than any other component.
674
So genes and depression are not about inevitability.
675
They're about vulnerability.
676
So what is the vulnerability about?
677
A few years ago, people discovered a particular gene that's really relevant to whether or not you get depression.
678
What was exciting about that?
679
It was a very clear finding.
680
It has since been replicated.
681
What else was exciting about it?
682
It made sense.
683
This was not some weirdo gene having something to do with how your big toe functions.
684
This was a gene having something to do with serotonin.
685
And this was a gene relevant to this whole reuptake, pumping business, all of that.
686
The main point of it is this gene comes in two different flavors.
687
Each one of us has one of the two versions.
688
And you immediately get this prediction, one of the versions, by all logic, should be predisposing to depression.
689
One of them is the one that should get you in more trouble.
690
So what does it look like when you go and study it?
691
The first paper that reported this a few years ago, and this I suspect is going to wind up being viewed
692
as the most important paper in biological psychiatry for a quarter of a century,
693
this was this massive study where a bunch of researchers looked at 17 ,000 kids growing up in New Zealand,
694
following them year after year, and looking at the genetic makeup of these individuals, and then asking in their early 20s,
695
who's got problems with major depression?
696
And then asking this critical question, what does it have to do with this gene?
697
Does the version of that gene that gets you into trouble, by all logic, is that going to set you up for more of a depression?
698
Are you more at risk for depression if you've got the bad version of the gene?
699
And back comes the finding, which is, no, it doesn't increase your risk.
700
You look here, and what's your likelihood of depression?
701
And you got the good version, and it's this likely, and you got the bad version, and it's this likely, doesn't make a difference.
702
Unless something else is going on.
703
Unless you have a history of exposure to major stressors.
704
And what you were able to do is quantify how many major stressors somebody's had during their childhood, their development, and that involves parental divorce,
705
and physical abuse, and death of family member, all that sort of thing.
706
And what you see is in the folks who have the good version of the gene,
707
as you have more and more of a history of major stressors, your risk of depression goes up, absolutely.
708
Now you look at the people with the bad version of the gene, and as you have more and more of a history of stress,
709
your risk of depression does this.
710
And when you look at the major history of stressors, a 30 -fold difference in the likelihood.
711
This is not about, oh, genes control our brains and genes control our behavior.
712
This is a gene
713
that is relevant to how readily we pick ourselves up after life has dumped us on our rear ends, how readily we recover from stressors.
714
What's the final piece of that story?
715
Glucocorticoids regulate the function of this gene.
716
All the pieces fall into place there.
717
Wonderfully logical.
718
And suddenly, you have a way of taking this whole world of psychological components of stress
719
and tying it into all that biochemistry, wonderfully integrated model.
720
OK, so in lots of ways, this is where the field is at at this point.
721
And what should mostly have come through here amid all this minutia
722
and factualism all of that is the role of stress
723
and the intersection of biology and the psychological stuff
724
and childhood as a very important time to imprint how vulnerable you are to depression for the rest of your life.
725
But again, the single thing I want to emphasize over and over implicitly, everything on that left side of the board there,
726
which is, this is not, oh, pull yourself together.
727
We all get depressed.
728
This is as real of a biological disorder as is diabetes.
729
And that's the thing I most want you guys to take off from here.
730
And in the context of a university setting is rife with major depression,
731
a community of high achieving type A individuals is rife with major depression.
732
It is all around us.
733
And amid it being all around us, there is this weird, corrosive inhibition, embarrassment, discomfort we have in the world of psychiatric diseases.
734
One of the greatest things, if you're a researcher with disease,
735
one of the things you pray for is for some powerful senator to have their loved one come down with your disease.
736
Because they're going to set up a foundation against special funding and advocacy groups and all of that, not for a psychiatric disorder.
737
That's the one where people don't talk about it.
738
And amid this screening biology, and this is a devastating disease, and all of that, in any place, and especially in a community like this,
739
where everyone is supposed to be golden and functioning and flawless and just gliding through life,
740
this is one of the hardest diseases for people to admit to.
741
So it is there.
742
It's all over the place, and it's biology.
743
And you should be no more inhibited about admitting
744
that you've got something going on that's funny with this type of gene than you would be to admit
745
that your pancreas isn't secreting insulin.
746
So let me stop at this point.
747
And again, unfortunately, I've got to sprint out the door.
748
Otherwise, I'm going to take questions. But thanks.
749
Thank you.
750
Thank you.
751
Thank you.
752
Thank you.
753
Thank you.
754
For more, please visit us at stanford .edu.

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15 كلمة من الفيديو تستحق التعلّم، مع النطق والمعنى:

الكلمةالنطقالمعنى
hormone اسم/ˈhoɹmoʊn/هُرْمُون
gene اسم/d͡ʒiːn/مُوَرِّثَة, جِين
depressed صفة/dɪˈpɹɛst/مُحْبَط, مُكْتَئِب
biology اسم/baɪˈɑ.lə.d͡ʒi/عِلْم اَلْأَحْيَاء, بِيُولُوجِيَا
disorder اسم/dɪsˈɔɹdɚ/اِخْتِلال, اِضْطِراب
symptom اسم/ˈsɪm(p)təm/عَرَض, عَلَامَة
awful صفة/ˈɔːfʊl/فَظِيع, أَرْبَد
biological صفة/ˌbaɪ.əˈlɑ.d͡ʒɪ.kəl/بِيُولُوجِيّ, أَحْيَائِي
psychology اسم/saɪˈkɑ.lə.d͡ʒi/سَيْكُولُوجْيَا, عِلْم النَّفْس
grief اسم/ɡɹiːf/غَمّ, حُزْن
ratio اسم/ˈɹeɪ.ʃoʊ/نِسْبَة
component اسم/kəmˈpoʊ.nənt/مُكَوِّن, جُزْء
receptor اسم/ɹɪˈsɛp.tə/مُسْتَقْبِل
topic اسم/ˈtɑpɪk/مَوْضُوع, مَوَاضِيع
chemistry اسم/ˈkɛm.ɪ.stɹi/كِيمِيَاء

الأفعال المركبة التي ستسمعها

الكلمةالنطقالمعنى
come out فعل/ˌkʌm ˈaʊt/خَرَجَ, غَادَرَ
come up with فعلجَاءَ بِـ, أَتَى بِـ
wake up فعل/ˌweɪk ˈʌp/صَحَا, اِسْتَيْقَظَ
fill out فعل/fɪl ˈaʊt/مَلَأَ
go away فعلاِبْتَعَدَ
go down فعلنَزَلَ
go out فعلخَرَجَ

جمل تستحق التكرار

جمل قصيرة وكاملة من الفيديو يمكنك استخدامها في الحديث اليومي:

  • What do you have to do?
  • What do you do then?
  • What's your theory have to be at that point?
  • Why would you want to do that?
  • You look here, and what's your likelihood of depression?

القواعد في هذا الفيديو

أكثر التراكيب التي يستخدمها المتحدث، مع العبارات نفسها من الفيديو:

التركيبفي الفيديو
المضارع التام have/has + اسم المفعول — حدث ماضٍ ما زال له أثر الآنhave not come · has happened · has just had
المبني للمجهول be + اسم المفعول — التركيز على ما يحدث لا على من يفعلهare extremely impaired · are flattened · is severely depressed
جمل الوصل who / which + جملة — معلومة إضافية عن شخص أو شيءprogeria, which is · problem, which is · someone who has

نطق يحتاج إلى انتباه

يستخدم المتحدث 156 من الصيغ المختصرة، مثل you've, you're, don't. انطقها بصيغتها القصيرة كما تسمعها.

  • أصوات “th”: pathway /ˈpæθˌweɪ/, thyroid /ˈθaɪ.ɹɔɪd/, hypothesis /haɪˈpɒθɪsɪs/
  • أصوات “sh” و“zh”: ratio /ˈɹeɪ.ʃoʊ/, aggression /əˈɡɹɛʃən/, shock /ʃɔk/, delusional /dɪˈluːʒənəl/, transition /tɹænˈzɪʃ.ən/
  • الكلمات الطويلة — انتبه لموضع النبر: biology /baɪˈɑ.lə.d͡ʒi/, biological /ˌbaɪ.əˈlɑ.d͡ʒɪ.kəl/, psychology /saɪˈkɑ.lə.d͡ʒi/, psychological /ˌsaɪ.kəˈlɑː.d͡ʒɪ.kl̩/, differently /ˈdɪf.ə.ɹənt.li/

أصوات يجدها متحدثو العربية صعبة:

  • /p/ — ليس /b/: انطقه مع نفخة هواء: depressed /dɪˈpɹɛst/, symptom /ˈsɪm(p)təm/, pathway /ˈpæθˌweɪ/, component /kəmˈpoʊ.nənt/, receptor /ɹɪˈsɛp.tə/
  • /v/ — ليس /f/: مع اهتزاز الأوتار الصوتية: recover /ɹɪˈkʌvɚ/, everyday /ˈɛvɹiˌdeɪ/, convince /kənˈvɪns/, vulnerability /ˌvʌln(ə)ɹəˈbɪlɪti/, involve /ɪnˈvɑlv/
  • تتابع الصوامت — لا تضف حركة بينها: depressed /dɪˈpɹɛst/, cortex /ˈkɔɹtɛks/, symptom /ˈsɪm(p)təm/, grief /ɡɹiːf/, component /kəmˈpoʊ.nənt/

كيف تتدرب بهذا الفيديو

  1. استمع إلى الفيديو كاملًا مرة واحدة دون أن تتكلم، ودوّن الكلمات التي لا تعرفها.
  2. ابدأ بسرعة 0.75×، وردّد جملة جملة، ثم عُد إلى السرعة العادية عندما يصبح الأمر سهلًا.
  3. سجّل صوتك وقارنه بالأصل، مع الانتباه إلى كلمات مثل hormone, gene, depressed.

ما هي تقنية التظليل الصوتي؟

التظليل الصوتي (Shadowing) تقنية تعلم لغة مدعومة علمياً، طُورت أصلاً لتدريب المترجمين الفوريين المحترفين. الطريقة بسيطة لكنها قوية: تستمع لصوت إنجليزي أصلي وتكرره فوراً بصوت عالٍ — كظل يتبع المتحدث بتأخير 1-2 ثانية. تُظهر الأبحاث تحسناً كبيراً في دقة النطق والتنغيم والإيقاع وربط الأصوات والاستماع والطلاقة.

تقنية الشادوينغ: اقرأ الدليل الكامل خطوة بخطوة →