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PSYCH 151: Stress and Psychiatry · Clinical Deep Dives

0:00
SPEAKER_01: Right.
0:00
SPEAKER_01: So I want you to picture a scene.
0:02
SPEAKER_01: You are in a clinical pharmacology laboratory and a woman is being injected with
0:07
SPEAKER_01: a massive dose of intravenous isoproteranol.
0:11
SPEAKER_00: Which, just to give some context, is a highly potent beta-adrenergic agonist.
0:15
SPEAKER_01: Exactly.
0:16
SPEAKER_01: I mean, it essentially acts exactly like a massive systemic dose of adrenaline.
0:21
SPEAKER_00: Right.
0:22
SPEAKER_01: Pharmacologically speaking, her heart rate should just absolutely skyrocket.
0:26
SPEAKER_01: I mean, it's a biological certainty, really.
0:28
SPEAKER_00: It is.
0:28
SPEAKER_00: It is actually a really venerable tool for testing autonomic physiology because
0:34
SPEAKER_00: the chemical reaction is just so universal.
0:37
SPEAKER_01: Yeah.
0:37
SPEAKER_01: The drug enters the bloodstream.
0:39
SPEAKER_01: It binds to the beta-1 receptors on the heart and the heart races.
0:43
SPEAKER_01: But during this specific infusion, something completely unexpected happens.
0:47
SPEAKER_01: The patient spontaneously closes her eyes and she begins to meditate.
0:51
SPEAKER_00: And what happens next?
0:52
SPEAKER_00: Well, it completely defies basic pharmacological expectations.
0:55
SPEAKER_01: It really does.
0:56
SPEAKER_00: The expected heart rate response,
0:57
SPEAKER_00: you know, that receptor driven spike we were talking about, is entirely blocked.
1:01
SPEAKER_00: Her heart rate actually drops
1:03
SPEAKER_00: while this adrenaline-like drug is literally being pumped directly into her veins.
1:07
SPEAKER_00: Her brain,
1:08
SPEAKER_00: just through the top-down cognitive act of meditation,
1:13
SPEAKER_00: completely overrides the bottom-up chemical reality of the drug.
1:17
SPEAKER_01: And, you know, they actually retested her later.
1:19
SPEAKER_01: They told her not to meditate this time and her heart rate spiked exactly as expected.
1:23
SPEAKER_00: Spot on.
1:23
SPEAKER_00: Yeah.
1:24
SPEAKER_01: So I want to start there today looking right at you,
1:27
SPEAKER_01: the listener,
1:28
SPEAKER_01: because that story proves something we often just treat as a,
1:31
SPEAKER_01: you know, a bit of a wellness cliche.
1:33
SPEAKER_00: Absolutely.
1:33
SPEAKER_00: The whole mind body connection thing.
1:35
SPEAKER_01: Right.
1:36
SPEAKER_01: But it isn't just an abstract concept.
1:38
SPEAKER_01: It is a measurable pharmacological reality.
1:41
SPEAKER_01: The neural signals generated by a state of calm can literally block
1:45
SPEAKER_01: the physiological effects of a chemical stressor right at the receptor level.
1:49
SPEAKER_00: Which is incredible.
1:50
SPEAKER_01: It is.
1:50
SPEAKER_01: And that brings us to the fundamental philosophy of this deep dive today.
1:54
SPEAKER_01: Psychiatry is the study of how brain,
1:57
SPEAKER_01: mind and experience interact and crucially how that entire process can go wrong.
2:01
SPEAKER_00: Because it's not just about neurotransmitters in a vacuum, is it?
2:05
SPEAKER_01: No, not at all.
2:05
SPEAKER_01: And it's not just about abstract emotions sort of floating around in the ether either.
2:09
SPEAKER_01: It is entirely about the collision of the two.
2:12
SPEAKER_00: And to really grasp the mechanics of that collision,
2:15
SPEAKER_00: I think we need a solid conceptual framework.
2:18
SPEAKER_01: Definitely.
2:18
SPEAKER_00: So imagine a brilliant Victorian era detective.
2:21
SPEAKER_00: Let's call him Medlock Holmes.
2:25
SPEAKER_00: And he walks into this very specific, strange place.
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SPEAKER_00: We'll call it the stress laboratory.
2:32
SPEAKER_01: I love this.
2:32
SPEAKER_01: So what does it look like?
2:33
SPEAKER_00: Well, there is a massive,
2:36
SPEAKER_00: almost steampunk-style brass apparatus right in the center of the room.
2:40
SPEAKER_00: And it's just systematically crushing these identical pieces of metal.
2:44
SPEAKER_01: Okay, so at first glance, the mystery for Holmes seems incredibly simple.
2:47
SPEAKER_01: I mean, it's just engineering, right?
2:49
SPEAKER_00: Exactly.
2:49
SPEAKER_00: You apply enough pressure, you apply enough force, and eventually the metal snaps.
2:53
SPEAKER_01: It's a completely linear equation.
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SPEAKER_01: Force equals breaking point.
2:56
SPEAKER_00: But here is the twist that Holmes quickly discovers.
2:59
SPEAKER_00: Human beings, well, they do not behave like identical pieces of metal on a workbench.
3:04
SPEAKER_01: Right, because you can take two people and you can expose them to the exact same trauma.
3:09
SPEAKER_01: I mean, the exact same loss, the same severe illness, or the same terrifying threat.
3:15
SPEAKER_01: And what happens?
3:15
SPEAKER_00: The trajectories are wildly different.
3:17
SPEAKER_01: Completely different.
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SPEAKER_00: One person develops severe debilitating depression.
3:22
SPEAKER_00: Another person becomes intensely anxious.
3:24
SPEAKER_01: Right, and then a third person is, you know, briefly distressed, sure, but...
3:28
SPEAKER_01: They recover quite quickly.
3:29
SPEAKER_00: Yeah.
3:30
SPEAKER_00: And a fourth person.
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SPEAKER_00: They might actually emerge from that exact same horrific event stronger
3:34
SPEAKER_00: with totally new capacities.
3:36
SPEAKER_01: Which brings us to the crucial question of this entire discussion, really.
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SPEAKER_01: Why does the exact same stressor produce such radically different outcomes
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SPEAKER_01: in different human beings?
3:46
SPEAKER_00: That is the mystery.
3:47
SPEAKER_01: It is.
3:48
SPEAKER_01: And today,
3:48
SPEAKER_01: our source material for solving that mystery is a deep dive into
3:52
SPEAKER_01: the clinical understanding of stress and psychiatry.
3:55
SPEAKER_01: We are being guided by the foundational concepts in Chapter 27.90 of Kaplan
4:00
SPEAKER_01: and Sedox, a comprehensive textbook of psychiatry.
4:03
SPEAKER_00: But we should be clear about our mission today.
4:05
SPEAKER_01: Oh, absolutely.
4:05
SPEAKER_01: This isn't just a regurgitation of textbook facts.
4:08
SPEAKER_00: No, this is a conceptual synthesis.
4:10
SPEAKER_00: We want to help you build mental models,
4:13
SPEAKER_00: clarify the actual physiological mechanisms at play,
4:16
SPEAKER_00: and ultimately strengthen your clinical reasoning.
4:19
SPEAKER_01: Okay, let's unpack this.
4:21
SPEAKER_01: Because to truly understand mental illness,
4:23
SPEAKER_01: we must first disentangle a word that has become so ubiquitous,
4:28
SPEAKER_01: so incredibly broad, that it actually obscures meaning rather than clarifying it.
4:33
SPEAKER_00: What's fascinating here is that the word is, of course, stress.
4:36
SPEAKER_01: Yeah, people say I'm stressed about missing a bus,
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SPEAKER_01: and they also say I'm stressed about a cancer diagnosis.
4:41
SPEAKER_00: Which is wild when you think about it historically.
4:43
SPEAKER_00: Before the 1930s, the term stress didn't even belong to psychology or medicine.
4:47
SPEAKER_01: Really?
4:48
SPEAKER_00: No, it was strictly an engineering term.
4:50
SPEAKER_00: It referred exactly to what our imaginary brass machine was doing,
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SPEAKER_00: the actual physical strain on a material object.
4:57
SPEAKER_01: So it was literal physical pressure.
4:59
SPEAKER_00: Exactly.
5:00
SPEAKER_00: The modern psychological construct only really took shape in the 20th century.
5:04
SPEAKER_00: And now patients use it constantly in the clinic.
5:07
SPEAKER_01: Oh, all the time.
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SPEAKER_01: They will list their acute and chronic stressors without you even having
5:11
SPEAKER_01: to prompt them in an interview.
5:13
SPEAKER_00: And you learn a tremendous amount by listening to how a patient recounts
5:18
SPEAKER_00: and perceives their ability to overcome those challenges.
5:21
SPEAKER_00: But clinically speaking, the slipperiness of the word is a major disadvantage.
5:26
SPEAKER_01: Because it's so vague.
5:27
SPEAKER_00: Right.
5:28
SPEAKER_00: When a patient says stress, are they referring to the event itself?
5:33
SPEAKER_00: Or are they referring to how their heart is racing?
5:35
SPEAKER_00: Or are they talking about the emotional suffering?
5:37
SPEAKER_01: It's just too muddy.
5:38
SPEAKER_01: We have to break down the clinical pathway into a much more precise framework.
5:42
SPEAKER_00: We do.
5:42
SPEAKER_01: We must separate it into four distinct concepts.
5:45
SPEAKER_01: First, there is the stressor.
5:47
SPEAKER_01: That is the external challenge or the end itself.
5:49
SPEAKER_01: Okay, step one.
5:51
SPEAKER_01: Second, there is the stress response.
5:53
SPEAKER_01: That is the physiological and psychological reaction,
5:56
SPEAKER_01: what the organism actually does about the challenge.
5:58
SPEAKER_00: Right, the internal reaction.
5:59
SPEAKER_01: Exactly.
6:00
SPEAKER_01: Third, we have distress.
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SPEAKER_01: And this is when the response actually becomes a pathological state of suffering.
6:06
SPEAKER_00: And finally, adaptation.
6:08
SPEAKER_00: The resolution or the adjustment to that challenge.
6:11
SPEAKER_01: So just to recap for you listening, stressor, stress response, distress, adaptation.
6:15
SPEAKER_00: That linear progression clarifies so much.
6:18
SPEAKER_00: And to understand how we arrived at this model,
6:21
SPEAKER_00: we have to look back at two massive pioneers in the field.
6:24
SPEAKER_00: First, Hans Slay.
6:27
SPEAKER_00: He essentially coined the medical use of the term stress in the mid 20th century.
6:32
SPEAKER_00: And what he observed in his animal studies was revolutionary,
6:35
SPEAKER_00: mainly because it directly contradicted the prevailing medical ideology of the time.
6:40
SPEAKER_01: Which was what?
6:41
SPEAKER_01: Exactly.
6:41
SPEAKER_00: Back then, the focus was entirely on specificity.
6:44
SPEAKER_00: It was the idea that specific pathogens elicited unique, specific pathologic responses.
6:50
SPEAKER_01: Ah, okay.
6:50
SPEAKER_01: So you get exposed to the tuberculosis bacterium, you get tuberculosis.
6:53
SPEAKER_00: Exactly.
6:54
SPEAKER_00: A specific lock and a specific key.
6:56
SPEAKER_01: Right.
6:56
SPEAKER_01: Highly specialized pathways for every single insult.
7:00
SPEAKER_00: But Salai noticed something else entirely.
7:02
SPEAKER_00: He saw that highly diverse stimuli,
7:04
SPEAKER_00: whether it was exposure to cold,
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SPEAKER_00: physical trauma,
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SPEAKER_00: or psychological threats,
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SPEAKER_00: they all seemed to result in common, orchestrated physiological changes.
7:12
SPEAKER_01: Interesting.
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SPEAKER_00: He called this the general adaptation system.
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SPEAKER_00: He proposed that any novelty or perturbation activates a systemic adaptive response,
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SPEAKER_00: primarily invoking the slower adrenocortical system.
7:22
SPEAKER_01: And he noted that if this unremitting stimulation continued,
7:26
SPEAKER_01: you would see diverse pathologic changes, right?
7:29
SPEAKER_00: He did.
7:29
SPEAKER_00: And while Sully focused on that slower adrenocortical system, we also have Walter Cannon.
7:36
SPEAKER_01: Ah, Walter Cannon.
7:37
SPEAKER_00: Yes.
7:38
SPEAKER_00: Cannon had a long abiding interest in the physiology of emotion.
7:41
SPEAKER_00: He was the pioneer of the sympathetic nervous system, the SNS.
7:45
SPEAKER_01: He was the one looking at the immediate short term fight or flight responses, wasn't he?
7:49
SPEAKER_00: Exactly.
7:50
SPEAKER_00: Cannon gave us the foundation for understanding how the body mobilizes immediately
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SPEAKER_00: in the face of a stressor.
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SPEAKER_01: So putting them together,
7:57
SPEAKER_01: early researchers were heavily influenced by this idea of
7:59
SPEAKER_01: a universal general adaptation.
8:02
SPEAKER_01: But, I mean, that led to a massive oversimplification, didn't it?
8:05
SPEAKER_00: It really did.
8:06
SPEAKER_01: They basically treated stress like an infectious virus.
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SPEAKER_01: The prevailing thought was that if you expose someone to enough of this,
8:13
SPEAKER_01: you know, stress virus, eventually they will catch a stress cold.
8:17
SPEAKER_00: Yeah, that the magnitude of the stressor alone dictated the illness.
8:20
SPEAKER_01: But that model is just too simple, isn't it?
8:22
SPEAKER_00: It is.
8:23
SPEAKER_00: And that exact oversimplification has historically hindered progress in psychiatry.
8:29
SPEAKER_00: It ignores a fundamental clinical distinction that we simply must make.
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SPEAKER_00: The difference between a cause and a trigger.
8:35
SPEAKER_01: Right.
8:36
SPEAKER_01: Cause versus trigger.
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SPEAKER_00: It is very, very difficult to prove that a stressor causes a complex illness out of nowhere.
8:43
SPEAKER_01: Yeah.
8:44
SPEAKER_00: Let's take a myocardial infarction, a heart attack.
8:46
SPEAKER_01: Okay.
8:47
SPEAKER_00: It usually only becomes evident after a long silent accumulation of coronary artery disease.
8:52
SPEAKER_00: You can't say the stress of a bad day at work caused the heart attack as
8:56
SPEAKER_00: if it magically conjured the plaque overnight.
8:58
SPEAKER_01: Right.
8:58
SPEAKER_01: The vulnerability was already there.
9:00
SPEAKER_01: The plumbing was already clobbed, so to speak.
9:02
SPEAKER_00: Exactly.
9:03
SPEAKER_00: Instead,
9:03
SPEAKER_00: we have to view the stressor as a trigger in a biologically
9:07
SPEAKER_00: or psychologically vulnerable individual.
9:09
SPEAKER_01: So the underlying illness is latent or maybe subclinical,
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SPEAKER_01: and the stress response acts as the catalyst that just brings it right to
9:15
SPEAKER_01: the surface.
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SPEAKER_00: And the clinical data illustrating this is just breathtaking.
9:19
SPEAKER_00: Consider a psychophysiological study done around the September 11 attacks
9:23
SPEAKER_00: the World Trade Center.
9:24
SPEAKER_01: Oh, wow.
9:25
SPEAKER_01: Okay.
9:25
SPEAKER_00: Researchers were tracking a 54-year-old man whose office was near the towers
9:30
SPEAKER_00: and they were recording his blood pressure twice a day.
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SPEAKER_00: Just routinely.
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SPEAKER_00: Routinely.
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SPEAKER_00: And his mean systolic blood pressure jumped 24 millimeters of mercury
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SPEAKER_00: and his diastolic jumped 12 millimeters immediately in the week following
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SPEAKER_00: the attacks.
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SPEAKER_01: That is a massive quantifiable physiological spike.
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SPEAKER_01: And it was triggered purely by a psychological and environmental stressor.
9:53
SPEAKER_00: Purely by the environment.
9:54
SPEAKER_00: And it goes even further than blood pressure.
9:56
SPEAKER_00: We see this quite dramatically with Takotsubo cardiomyopathy.
9:59
SPEAKER_01: Ah, yes.
10:01
SPEAKER_01: Literal heartbreak syndrome.
10:02
SPEAKER_00: Exactly.
10:03
SPEAKER_00: And a reversible cardiomyopathy elicited purely by psychologically stressful events.
10:07
SPEAKER_01: And when you actually look at the echocardiograms of these patients,
10:10
SPEAKER_01: you can see a profound structural change in the heart, can't you?
10:13
SPEAKER_00: You can.
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SPEAKER_00: The distal left ventricular chamber actually balloons out.
10:17
SPEAKER_00: It ends up looking like a Japanese octopus trap.
10:19
SPEAKER_01: Which is where the name tokotsubo comes from, right?
10:21
SPEAKER_00: Quite right.
10:22
SPEAKER_00: And to be clear,
10:24
SPEAKER_00: the psychological stress didn't build the heart muscle,
10:27
SPEAKER_00: but the massive surge of catecholamines triggered
10:30
SPEAKER_00: a profound localized systolic dysfunction.
10:32
SPEAKER_01: So if stress is the trigger,
10:34
SPEAKER_01: whether or not the gun goes off depends entirely on the vulnerability of
10:38
SPEAKER_01: the person holding it.
10:39
SPEAKER_00: Precisely.
10:40
SPEAKER_01: Which brings us nicely to vulnerability and resilience.
10:44
SPEAKER_01: In pop psychology, we often talk about resilience as just being, you know, tough or having grit.
10:49
SPEAKER_00: Just powering through.
10:50
SPEAKER_01: Yeah, exactly.
10:51
SPEAKER_01: But clinically, it is a much more complex picture.
10:54
SPEAKER_01: It's not just a static personality trait.
10:57
SPEAKER_01: It is an ecological system.
10:59
SPEAKER_00: An ecological system.
11:00
SPEAKER_01: Explain that for us.
11:01
SPEAKER_01: Because...
11:02
SPEAKER_01: If behavior like information seeking or problem solving is just one layer,
11:07
SPEAKER_01: what are the other scales we need to be looking at?
11:09
SPEAKER_00: Resilience is a process that crosses multiple interacting scales.
11:13
SPEAKER_00: You have biological systems,
11:15
SPEAKER_00: psychological systems,
11:16
SPEAKER_00: the social environment, the built environment, and the natural environment.
11:20
SPEAKER_00: And they all interact.
11:20
SPEAKER_01: So it's layers upon layers.
11:22
SPEAKER_00: Exactly.
11:23
SPEAKER_00: So a vulnerability in the biological scale,
11:26
SPEAKER_00: let's say a genetic predisposition to high anxiety,
11:30
SPEAKER_00: might be entirely buffered by a massive protective factor in
11:34
SPEAKER_00: the social environment scale,
11:36
SPEAKER_00: like an incredibly supportive family and a stable income.
11:40
SPEAKER_01: Right.
11:40
SPEAKER_01: I mean, you might have excellent psychological coping skills,
11:43
SPEAKER_01: but if your built environment is literally a war zone,
11:47
SPEAKER_01: your resilience will eventually fail.
11:48
SPEAKER_00: It will.
11:49
SPEAKER_00: It is the complex biopsychosocial ecological system at work.
11:54
SPEAKER_00: If a patient is struggling,
11:56
SPEAKER_00: the failure of resilience might not be a failure of their internal willpower at all.
12:00
SPEAKER_00: It might be a total failure of their environment.
12:02
SPEAKER_01: Here's where it gets really interesting, though.
12:04
SPEAKER_01: Now that we have the framework,
12:05
SPEAKER_01: you know,
12:05
SPEAKER_01: stressors trigger distress in vulnerable systems,
12:08
SPEAKER_01: let's get into the actual biological mechanics.
12:11
SPEAKER_00: Let's do it.
12:12
SPEAKER_01: How does the brain actually process these stressors to create that distress?
12:15
SPEAKER_01: We need to look at the two main pathways, the fast pathway and the slow pathway.
12:20
SPEAKER_01: Let's start with the immediate response.
12:22
SPEAKER_00: Okay, the fast pathway.
12:23
SPEAKER_00: This is the domain of the autonomic nervous system, specifically the sympathetic branch.
12:27
SPEAKER_00: When a stressor disrupts equilibrium, this system is activated instantly.
12:32
SPEAKER_00: It triggers the release of catecholamines.
12:34
SPEAKER_00: So that's noradrenaline, dopamine and serotonin.
12:37
SPEAKER_01: This is your classic adrenaline rush.
12:39
SPEAKER_00: Exactly.
12:40
SPEAKER_00: Your heart rate spikes,
12:41
SPEAKER_00: your cardiovascular activity increases,
12:43
SPEAKER_00: your pupils dilate and your attention violently narrows to focus entirely on
12:47
SPEAKER_00: the threat.
12:48
SPEAKER_01: Your body is basically making all its energy available
12:51
SPEAKER_01: for immediate explosive action, run or fight.
12:54
SPEAKER_00: It is instantaneous and it's mediated by direct neural connections.
12:58
SPEAKER_00: But running alongside this and taking just a bit longer to fully manifest is the slow pathway.
13:03
SPEAKER_01: The neuroendocrine cascade.
13:05
SPEAKER_00: Yes.
13:06
SPEAKER_00: This is the domain of the hypothalamic pituitary adrenal axis or the HPA axis.
13:11
SPEAKER_01: This cascade is just vital for clinical reasoning.
13:13
SPEAKER_01: Let us map it out for the listener.
13:14
SPEAKER_01: Go for it.
13:21
SPEAKER_01: Or CRH.
13:23
SPEAKER_01: Then that CRH travels a very short distance to the anterior pituitary gland,
13:27
SPEAKER_01: which then releases adrenocorticotropic hormone,
13:29
SPEAKER_01: or ACTH, into the general bloodstream.
13:32
SPEAKER_00: Following so far.
13:33
SPEAKER_01: And finally,
13:34
SPEAKER_01: that ACTH travels all the way down to the adrenal cortex,
13:37
SPEAKER_01: which is sitting right on top of the kidneys, which finally releases cortisol.
13:42
SPEAKER_00: Exactly.
13:42
SPEAKER_00: So stressor to hypothalamus to CRH to pituitary to ACTH to adrenal cortex to cortisol.
13:51
SPEAKER_01: The essential question here, though, is why this system exists.
13:54
SPEAKER_01: I mean, what is the evolutionary logic of cortisol?
13:58
SPEAKER_00: Well, its primary actions are to promote energy utilization
14:01
SPEAKER_00: and increase cardiovascular activity to support that fight or flight response.
14:06
SPEAKER_00: But crucially,
14:07
SPEAKER_00: it also actively inhibits functions that are not immediately necessary for surviving
14:11
SPEAKER_00: a crisis.
14:12
SPEAKER_01: Oh, like what?
14:13
SPEAKER_00: It temporarily shuts down growth, reproduction and specific aspects of immunity.
14:17
SPEAKER_01: Right, because if you're running from a literal predator,
14:20
SPEAKER_01: your body shouldn't be wasting precious metabolic energy on digesting your lunch or,
14:24
SPEAKER_01: you know, making antibodies for a cold you might get next week.
14:26
SPEAKER_00: Or reproductive functions, yeah.
14:28
SPEAKER_01: Exactly.
14:28
SPEAKER_01: You divert all power to the engines to survive the next five minutes.
14:32
SPEAKER_00: And this brings us right back to Medlock Holmes' first principle in our laboratory.
14:36
SPEAKER_00: The stress response is not inherently pathological.
14:39
SPEAKER_01: It's actually a brilliant system.
14:41
SPEAKER_00: It is.
14:42
SPEAKER_00: It's a highly conserved, adaptive, life saving mechanism designed to restore homeostasis.
14:48
SPEAKER_00: It is a biological triumph.
14:50
SPEAKER_01: So when does it become a problem?
14:52
SPEAKER_00: The pathology,
14:53
SPEAKER_00: the distress,
14:54
SPEAKER_00: only begins when this perfectly designed system goes wrong,
14:58
SPEAKER_00: when it becomes excessive or prolonged or repeatedly activated,
15:02
SPEAKER_00: or when the negative feedback loops,
15:05
SPEAKER_00: which usually involve the hypothalamus,
15:07
SPEAKER_00: pituitary,
15:08
SPEAKER_00: and hippocampus telling the system to shut off,
15:10
SPEAKER_00: when they fail to regulate that cortisol cascade.
15:13
SPEAKER_01: Wait, I want to clarify something here.
15:14
SPEAKER_01: We talk about the stress response as if it's just one big switch the brain flips,
15:18
SPEAKER_01: but surely the brain differentiates between types of stressors, right?
15:22
SPEAKER_00: Oh, absolutely.
15:23
SPEAKER_01: Because bleeding out from a physical wound is a very different biological emergency
15:28
SPEAKER_01: than, say, being humiliated in public during a presentation?
15:31
SPEAKER_00: You've hit on a crucial neurobiological distinction there.
15:34
SPEAKER_00: There's no single uniform stress response in the brain.
15:37
SPEAKER_01: Okay.
15:38
SPEAKER_00: Physical stressors like blood lies or hypothermia,
15:41
SPEAKER_00: they preferentially recruit the brainstem and hypothalamic systems.
15:45
SPEAKER_01: Because they're primal.
15:46
SPEAKER_00: Exactly.
15:47
SPEAKER_00: They are primal physiological emergencies that bypass higher order processing entirely.
15:54
SPEAKER_00: But psychological stressors like intense embarrassment or
15:57
SPEAKER_00: a looming financial crisis, they engage entirely different networks.
16:00
SPEAKER_01: Like the cortex.
16:01
SPEAKER_00: Yes.
16:02
SPEAKER_00: They recruit the amygdala for emotion,
16:04
SPEAKER_00: the hippocampus for learning and memory context,
16:07
SPEAKER_00: and the prefrontal cortex for decision making and appraisal.
16:10
SPEAKER_01: And I imagine there's significant variability
16:12
SPEAKER_01: in how those higher order networks function, right?
16:15
SPEAKER_01: Not just between individuals, but between sexes.
16:17
SPEAKER_00: Yes.
16:18
SPEAKER_00: And that is a huge area of modern research.
16:20
SPEAKER_01: Because we've historically assumed in medicine
16:23
SPEAKER_01: that females were more biologically vulnerable to life stressors,
16:27
SPEAKER_01: largely based on epidemiological rates of anxiety and depression.
16:30
SPEAKER_00: We did.
16:31
SPEAKER_00: And that assumption is currently being radically dismantled.
16:33
SPEAKER_01: Hmm.
16:34
SPEAKER_00: Emerging animal research is showing something truly fascinating.
16:37
SPEAKER_00: Male rats actually exhibit greater variability in neurotransmitter response
16:41
SPEAKER_00: to stress than females.
16:43
SPEAKER_01: Wow, really?
16:45
SPEAKER_01: That completely challenges old assumptions.
16:47
SPEAKER_00: It really does.
16:47
SPEAKER_00: It highlights how rudimentary our understanding of the interaction between sex
16:51
SPEAKER_00: and stress truly is.
16:52
SPEAKER_01: If animal models are showing sexually dimorphic responses to stress,
16:56
SPEAKER_01: that has massive implications for how we understand the pathophysiology
17:01
SPEAKER_01: of stress-related disorders in humans.
17:03
SPEAKER_00: Huge implications.
17:04
SPEAKER_00: We desperately need sex-specific models of psychiatric illness rather
17:08
SPEAKER_00: than just treating the male response as the default baseline.
17:12
SPEAKER_01: We absolutely do.
17:13
SPEAKER_01: And alongside sex, we also must consider duration.
17:16
SPEAKER_01: I mean, acute stress evokes rapid transient alterations in catecholamine release.
17:21
SPEAKER_01: But chronic stress does something fundamentally different, doesn't it?
17:25
SPEAKER_00: It does.
17:26
SPEAKER_00: Chronic stress induces sustained effects on neuronal firing and gene activation.
17:31
SPEAKER_00: The mechanism isn't just, you know, more of the same.
17:34
SPEAKER_00: Chronic stress shifts into altering how the cells themselves function on a genetic level.
17:38
SPEAKER_01: Which bridges us into one of the most complex yet vital clinical concepts,
17:42
SPEAKER_01: psychoneuroimmunology.
17:43
SPEAKER_00: The mind-body-immune matrix, if we connect this to the bigger picture.
17:47
SPEAKER_01: Yes.
17:47
SPEAKER_01: For a long time,
17:48
SPEAKER_01: the immune system was taught as this completely independent,
17:51
SPEAKER_01: autonomous defense force floating around the body,
17:53
SPEAKER_01: completely separate from the nervous system.
17:55
SPEAKER_00: And we now know that is entirely false.
17:58
SPEAKER_00: Psychoneuroimmunology studies the profound bi-directional interactions between
18:03
SPEAKER_00: the brain, behavior, and the immune system.
18:05
SPEAKER_01: So to understand this, we briefly need to review the immune system's two main branches, right?
18:10
SPEAKER_00: Exactly.
18:10
SPEAKER_00: First, you have innate immunity.
18:12
SPEAKER_00: This is your nonspecific first responder.
18:14
SPEAKER_00: You've got macrophages and granulocytes
18:17
SPEAKER_00: that release pro-inflammatory cytokines like TNF-alpha and IL-6
18:21
SPEAKER_00: to induce inflammation and consume cellular debris.
18:24
SPEAKER_01: Right.
18:24
SPEAKER_01: And then you have specific immunity, which is acquired.
18:27
SPEAKER_00: Yes.
18:27
SPEAKER_00: B cells secreting antibodies, T cells killing virus harboring cells.
18:31
SPEAKER_01: And the cytokines,
18:32
SPEAKER_01: those interleukins,
18:33
SPEAKER_01: act as the chemical communication network to coordinate all of this.
18:37
SPEAKER_01: But how does the brain actually talk to these immune cells?
18:40
SPEAKER_01: I mean, how does a thought influence a T cell?
18:43
SPEAKER_00: Well, there are two physical biological connections.
18:45
SPEAKER_00: The first is the autonomic nervous system, the fast pathway we discussed.
18:49
SPEAKER_00: Okay.
18:49
SPEAKER_00: And this isn't abstract.
18:50
SPEAKER_00: It is an anatomical reality.
18:52
SPEAKER_00: Sympathetic nerves literally run from the brainstem down the spinal cord
18:57
SPEAKER_00: and physically penetrate immune organs like the spleen and the thymus.
19:00
SPEAKER_01: Wait, they physically wire into the immune organs?
19:04
SPEAKER_00: They do.
19:04
SPEAKER_00: They contact the tissues where immune cells develop.
19:07
SPEAKER_00: The nerves release norepinephrine,
19:09
SPEAKER_00: and the immune cells actually have receptors on their surface
19:12
SPEAKER_00: to bind those exact neurotransmitters.
19:15
SPEAKER_01: That is incredible.
19:16
SPEAKER_00: Furthermore,
19:17
SPEAKER_00: sympathetic nerves penetrate the adrenal gland,
19:20
SPEAKER_00: causing the release of epinephrine directly into the bloodstream,
19:23
SPEAKER_00: which then circulates and binds to immune cells.
19:26
SPEAKER_01: So it's hardwired.
19:27
SPEAKER_01: The brain is literally plugged into the immune system.
19:30
SPEAKER_01: And what does this sympathetic activation actually do to the immune cells?
19:34
SPEAKER_00: Okay.
19:34
SPEAKER_00: Okay.
19:34
SPEAKER_00: Okay.
19:59
SPEAKER_01: Wow.
20:00
SPEAKER_01: So that is the autonomic link.
20:01
SPEAKER_01: And the second connection is via the neuroendocrine axis, the HPA system, right?
20:05
SPEAKER_00: Yes.
20:07
SPEAKER_00: Cortisol,
20:07
SPEAKER_00: the end product of that slow pathway,
20:10
SPEAKER_00: profoundly suppresses the cellular immune response.
20:14
SPEAKER_01: This is exactly why synthetic analogs of cortisol,
20:17
SPEAKER_01: like prednisone,
20:18
SPEAKER_01: are prescribed in medicine to suppress excessive immune responses
20:21
SPEAKER_01: during autoimmune flare-ups.
20:23
SPEAKER_00: Quite right.
20:24
SPEAKER_00: And crucially, the communication goes both ways.
20:27
SPEAKER_00: The immune cells themselves can produce neuroendocrine peptides like endorsins and ACTH.
20:33
SPEAKER_01: So they're using the exact same molecular language as the brain.
20:37
SPEAKER_00: Exactly.
20:37
SPEAKER_00: Which leads to this incredible, highly consequential clinical concept of sickness behaviors.
20:43
SPEAKER_01: Oh, I find this fascinating.
20:44
SPEAKER_01: Walk me through sickness behaviors
20:46
SPEAKER_01: because this fundamentally changes how we view psychiatric symptoms.
20:50
SPEAKER_00: Okay, so when peripheral immune activation occurs,
20:52
SPEAKER_00: say you get a severe viral infection,
20:54
SPEAKER_00: macrophages release inflammatory cytokines, TNF, IL-1, and IL-6.
21:00
SPEAKER_01: The usual suspects.
21:01
SPEAKER_00: Right.
21:01
SPEAKER_00: And these cytokines don't just stay in the body.
21:03
SPEAKER_00: They cross the blood-brain barrier and activate the HPA system by triggering
21:08
SPEAKER_00: the central release of CRH.
21:09
SPEAKER_01: Ah, so they go into the brain.
21:10
SPEAKER_00: Yes.
21:11
SPEAKER_00: When the brain gets bathed in these inflammatory cytokines, it alters your behavior.
21:15
SPEAKER_01: You see reductions in physical activity,
21:17
SPEAKER_01: a complete loss of interest in exploring the environment,
21:20
SPEAKER_01: social withdrawal, decreased food intake, and a loss of libido, right?
21:24
SPEAKER_00: Exactly.
21:25
SPEAKER_00: You get profound fatigue, low mood.
21:28
SPEAKER_00: In cognitive impairment.
21:29
SPEAKER_01: Now, if you have the flu, this is a highly adaptive survival mechanism.
21:33
SPEAKER_01: Your body is forcing you to withdraw,
21:35
SPEAKER_01: conserve energy and rest so
21:38
SPEAKER_01: the immune system can utilize all available metabolic resources to fight
21:42
SPEAKER_01: the physical virus.
21:43
SPEAKER_00: Keeping you in bed so you don't waste energy running around.
21:45
SPEAKER_01: Right.
21:46
SPEAKER_01: But and this is the terrifying part because the pathways are bidirectional.
21:50
SPEAKER_01: Severe psychological stress can trigger this exact same release of inflammatory cytokines.
21:55
SPEAKER_01: Yes.
21:56
SPEAKER_01: Your brain perceives a psychological threat,
21:58
SPEAKER_01: triggers the stress pathways,
21:59
SPEAKER_01: which alters immune function and spike cytokines,
22:02
SPEAKER_01: which then cross back into the brain and induce sickness behaviors.
22:05
SPEAKER_00: But there is no virus.
22:07
SPEAKER_01: Exactly.
22:07
SPEAKER_01: There is no virus.
22:08
SPEAKER_01: The sickness behaviors manifest clinically as profound fatigue, social withdrawal and low mood.
22:13
SPEAKER_01: It looks exactly like major depression.
22:15
SPEAKER_00: It is devastating when it's triggered by a psychosocial stressor rather than
22:20
SPEAKER_00: a pathogen because the sickness never resolves.
22:23
SPEAKER_00: The stressor is still there.
22:24
SPEAKER_01: It forces us to view a subset of depression not purely as
22:28
SPEAKER_01: a primary neurotransmitter deficit, but as a secondary inflammatory response.
22:33
SPEAKER_00: It absolutely does.
22:35
SPEAKER_00: And speaking of expanding our view of biology,
22:37
SPEAKER_00: we must also look at the gastrointestinal microbiome.
22:40
SPEAKER_01: Yes.
22:41
SPEAKER_01: I really wanted to ask about gut feelings because we use that phrase constantly,
22:44
SPEAKER_01: but it represents a measurable physiological reality,
22:47
SPEAKER_00: doesn't it?
22:47
SPEAKER_00: It does.
22:49
SPEAKER_00: 70% of the immune system is comprised of gut-associated lymphoid tissue.
22:52
SPEAKER_01: 70%?
22:53
SPEAKER_01: Yeah.
22:54
SPEAKER_00: The gut is a massive immune organ acting as a barrier.
22:58
SPEAKER_00: The brain acts on gastrointestinal and immune functions to shape the microbiome.
23:03
SPEAKER_00: But crucially,
23:04
SPEAKER_00: the gut microbes themselves produce neurotransmitters of metabolites that interact
23:08
SPEAKER_00: with the neuroendocrine and immune systems.
23:11
SPEAKER_00: They even control the permeability of the intestinal lining and the blood-brain barrier.
23:15
SPEAKER_01: And chronic stress completely disrupts this ecosystem, doesn't it?
23:19
SPEAKER_00: Oh, completely.
23:20
SPEAKER_00: Animal studies show that exposure to acute and chronic stress literally alters
23:25
SPEAKER_00: the relative proportions of the main microbiota phyla in the gut.
23:28
SPEAKER_01: So the actual populations of bacteria shift?
23:31
SPEAKER_00: Yes.
23:32
SPEAKER_00: And this dysbiosis, this imbalance, influences how the host responds to future stress.
23:38
SPEAKER_00: In humans,
23:39
SPEAKER_00: chronic gut disorders with microbiome dysbiosis are heavily associated
23:43
SPEAKER_00: with behavioral changes,
23:45
SPEAKER_00: heightened stress responsiveness, and increased anxiety and depressive symptoms.
23:49
SPEAKER_01: Which naturally leads us to ask,
23:51
SPEAKER_01: how does chronic stress leave a lasting mark even long after the stressor is gone?
23:56
SPEAKER_01: If trauma fundamentally changes the gut, what else is it changing?
24:00
SPEAKER_00: The answer there lies in epigenetics and telomeres.
24:03
SPEAKER_01: Let's really break down epigenetics because it's a term thrown around a lot
24:06
SPEAKER_01: in popular science, often incorrectly.
24:08
SPEAKER_00: Very true.
24:09
SPEAKER_01: Epigenetics provides the mechanism for how the environment changes gene expression
24:12
SPEAKER_01: without altering the underlying DNA sequence itself.
24:15
SPEAKER_01: I like to think of it like a physical lock on a door.
24:17
SPEAKER_00: I like that analogy.
24:18
SPEAKER_01: Right.
24:19
SPEAKER_01: So the DNA sequence is the room, the potential function of the cell.
24:23
SPEAKER_01: But epigenetic changes, like DNA methylation, act as heavy padlocks placed on the door.
24:29
SPEAKER_01: The room is still there, but the cell can no longer enter it and use that genetic information.
24:35
SPEAKER_00: And the environment physically attaches these locks.
24:38
SPEAKER_01: Exactly.
24:38
SPEAKER_00: That is a very precise analogy.
24:40
SPEAKER_00: The clinical literature highlights a famous prospective study from New Zealand
24:45
SPEAKER_00: that followed 1,000 subjects from age 3 to 26.
24:48
SPEAKER_01: Oh, the Dundun study.
24:50
SPEAKER_00: Yes.
24:51
SPEAKER_00: They were looking at the promoter region of the serotonin transporter gene,
24:55
SPEAKER_00: and what they found was a powerful gene-by-environment interaction.
24:59
SPEAKER_01: Right.
24:59
SPEAKER_01: They found that individuals who were homozygous for the short allele of
25:03
SPEAKER_01: that promoter region were significantly more likely to become depressed
25:06
SPEAKER_01: and suicidal.
25:07
SPEAKER_00: But, and this is the critical part,
25:09
SPEAKER_00: only in response to life stressors, particularly childhood maltreatment.
25:13
SPEAKER_01: So neither the genetic short allele alone nor
25:15
SPEAKER_01: the environmental stress alone dictated the outcome.
25:18
SPEAKER_00: Exactly.
25:19
SPEAKER_00: It was the interaction.
25:20
SPEAKER_00: The environmental stressor interacted with the genetic vulnerability to produce the disease.
25:24
SPEAKER_01: We see this physical locking mechanism Clearly in animal models too, don't we?
25:29
SPEAKER_00: We do.
25:30
SPEAKER_00: There's a brilliant study in socially defeated mice that looked at DNA methylation.
25:35
SPEAKER_01: Social defeat, so chronic stress.
25:36
SPEAKER_00: Right.
25:37
SPEAKER_00: Chronic social defeat stress actually increased the transcription of
25:40
SPEAKER_00: a specific DNA methyltransferase, an enzyme called DNMT3A, in the nucleus accumbens.
25:46
SPEAKER_01: And what did that do?
25:47
SPEAKER_00: This epigenetic change physically altered the DNA expression,
25:51
SPEAKER_00: resulting in increased depressive behaviors.
25:54
SPEAKER_00: But when researchers selectively blocked DNA methylation in that region,
25:58
SPEAKER_00: the effect was entirely reversed.
26:00
SPEAKER_01: Wait, reverse?
26:01
SPEAKER_00: Reversible chemical tags in the DNA that change behavior.
26:04
SPEAKER_00: The environmental trauma caused the tag, and blocking it stopped the behavior.
26:08
SPEAKER_01: That is just phenomenal.
26:09
SPEAKER_01: And alongside these epigenetic locks, we absolutely must consider telomeres.
26:14
SPEAKER_00: Ah, telomeres.
26:15
SPEAKER_01: Yeah, telomeres are the protective DNA sequences at the very ends of our chromosomes.
26:20
SPEAKER_01: They act almost like those little plastic aglets at the ends of shoelaces
26:23
SPEAKER_01: to keep them from fraying.
26:25
SPEAKER_00: Yes, great visual.
26:26
SPEAKER_01: Every time a cell divides, those telomeres get a little shorter.
26:29
SPEAKER_01: When they get too short, the cell becomes senescent.
26:32
SPEAKER_01: It stops functioning properly and basically begins to die.
26:35
SPEAKER_01: It is the literal cellular clock of aging.
26:38
SPEAKER_00: And senescent immune cells, they don't just quietly fade away, do they?
26:42
SPEAKER_01: No, they don't.
26:42
SPEAKER_00: They actually produce excess pro-inflammatory cytokines.
26:47
SPEAKER_00: And there is mounting evidence that chronic psychological stress
26:50
SPEAKER_00: and stress-related disorders literally accelerate telomere shortening
26:54
SPEAKER_00: in immune cells.
26:55
SPEAKER_01: Which provides a direct biological mechanism for why chronic stress
26:59
SPEAKER_01: and severe psychiatric illness are associated with premature aging.
27:03
SPEAKER_01: And an earlier onset of age-related diseases.
27:06
SPEAKER_00: It's sobering.
27:07
SPEAKER_01: It is.
27:08
SPEAKER_01: Chronic stress is quite literally aging the cells of the immune system faster.
27:12
SPEAKER_00: So we have built this massive mechanistic model now.
27:15
SPEAKER_00: We have the fast autonomic path,
27:17
SPEAKER_00: the slow neuroendocrine path,
27:18
SPEAKER_00: the bidirectional immune cytokine loop,
27:21
SPEAKER_00: the microbiome, epigenetic locks, and telomere shortening.
27:24
SPEAKER_01: That's a lot of biology.
27:26
SPEAKER_00: It is.
27:27
SPEAKER_00: So let's transition from the cellular to the clinical.
27:30
SPEAKER_00: If trauma fundamentally changes the physical structure of a cell's DNA,
27:34
SPEAKER_00: what does a brain under that kind of chronic structural siege actually look like in
27:39
SPEAKER_00: a hospital waiting room?
27:40
SPEAKER_01: Right.
27:41
SPEAKER_01: Let's look at cardiovascular disease first.
27:43
SPEAKER_01: We know depression is associated with an increased risk of coronary artery disease
27:47
SPEAKER_01: and much worse outcomes after a heart attack.
27:49
SPEAKER_00: We do.
27:50
SPEAKER_01: For a long time,
27:51
SPEAKER_01: we thought of cardiovascular disease purely as a plumbing issue,
27:55
SPEAKER_01: passive pipes getting clogged with fat.
27:57
SPEAKER_01: But atherosclerosis is now understood to be an active inflammatory process.
28:01
SPEAKER_00: Exactly.
28:03
SPEAKER_00: Activated macrophages in
28:04
SPEAKER_00: the blood vessels secrete pro-inflammatory cytokines like IL-1, IL-6, and TNF.
28:10
SPEAKER_00: And this causes the expression of cellular adhesion molecules on the vascular walls.
28:14
SPEAKER_01: Which basically means...
28:15
SPEAKER_00: To put it simply, it makes the interior of the blood vessels sticky.
28:18
SPEAKER_01: Sticky blood vessels.
28:19
SPEAKER_01: And as we've established,
28:20
SPEAKER_01: psychological and physical stressors lead to an increased release
28:24
SPEAKER_01: of those exact pro-inflammatory cytokines.
28:26
SPEAKER_01: So, stress and depressed mood trigger inflammation,
28:30
SPEAKER_01: which makes the blood vessels sticky,
28:32
SPEAKER_01: which recruits more immune cells, which causes more arterial damage.
28:36
SPEAKER_01: It forms this vicious cycle promoting cardiovascular disease.
28:40
SPEAKER_00: And the data backs this up.
28:41
SPEAKER_00: A study of over 1,700 Canadians showed depression
28:45
SPEAKER_00: and elevated inflammatory markers actively predicted an increased risk
28:49
SPEAKER_00: of coronary artery disease.
28:50
SPEAKER_01: It's all connected.
28:51
SPEAKER_01: And we see similar immune dysregulation in infectious and autoimmune diseases, too.
28:55
SPEAKER_00: We do.
28:56
SPEAKER_00: Chronic stress and depression are associated with decreases in cellular and innate immunity.
29:01
SPEAKER_00: This makes people measurably more susceptible to viral diseases like herpes simplex
29:06
SPEAKER_00: or just the common cold.
29:07
SPEAKER_01: But hold on.
29:08
SPEAKER_01: What about autoimmune disorders like rheumatoid arthritis?
29:10
SPEAKER_01: I actually want to push back on the mechanism here a little bit.
29:12
SPEAKER_00: OK, go ahead.
29:13
SPEAKER_01: If stress releases cortisol and cortisol is
29:15
SPEAKER_01: a powerful immunosuppressant like prednisone,
29:18
SPEAKER_01: shouldn't chronic stress actually improve autoimmune conditions by suppressing
29:22
SPEAKER_01: the immune system?
29:23
SPEAKER_01: Why does stress make rheumatoid arthritis worse?
29:26
SPEAKER_00: That is a brilliant physiological paradox.
29:30
SPEAKER_00: Okay, so the thermostat regulates the furnace.
29:32
SPEAKER_00: Makes sense.
29:54
SPEAKER_00: Ah, I see.
29:54
SPEAKER_00: Ah, I see.
30:16
SPEAKER_01: That makes perfect sense.
30:18
SPEAKER_01: So chronic stress provokes increases in the production of IL-6.
30:21
SPEAKER_01: Because the HPA axis isn't producing enough cortisol to shut it down,
30:25
SPEAKER_01: or the receptors are numb, that IL-6 just runs rampant.
30:28
SPEAKER_00: Exactly.
30:28
SPEAKER_00: And in rheumatoid arthritis,
30:30
SPEAKER_00: IL-6 levels correlate directly with disease symptoms,
30:34
SPEAKER_00: severe fatigue, joint destruction, pain, and functional limitations.
30:38
SPEAKER_00: Wow.
30:38
SPEAKER_00: So if a patient with rheumatoid arthritis is depressed
30:41
SPEAKER_00: and undergo severe psychosocial stress,
30:43
SPEAKER_00: they have exaggerated increases in IL-6,
30:45
SPEAKER_00: which actively predicts the physical progression of their joint disease.
30:49
SPEAKER_01: The clinical reality of the mind-body connection is just undeniable there.
30:52
SPEAKER_01: We even see it in dermatology, specifically with atopic dermatitis.
30:57
SPEAKER_01: It's a chronic relapsing skin disease characterized
30:59
SPEAKER_01: by impaired epidermal barrier function,
31:02
SPEAKER_01: inflammatory infiltrates, and just excessive itching.
31:05
SPEAKER_00: And psychological stress directly aggravates it, doesn't it?
31:08
SPEAKER_01: It does.
31:08
SPEAKER_01: Skin biopsies from patients show elevated Th2 cells,
31:12
SPEAKER_01: specific cytokines,
31:13
SPEAKER_01: and eosinophils with elevated IgE production, specifically in response to stress.
31:18
SPEAKER_01: It literally alters the epidermal barrier.
31:21
SPEAKER_01: The stress causes psychogenic ditch.
31:23
SPEAKER_00: And interestingly,
31:23
SPEAKER_00: treating the psychological stress with CBT or antidepressants physically improves
31:28
SPEAKER_00: the skin condition.
31:29
SPEAKER_01: It's amazing.
31:30
SPEAKER_01: So we see clearly how stress triggers physical illness.
31:34
SPEAKER_01: But this brings us to a major clinical hurdle.
31:37
SPEAKER_00: Which is?
31:38
SPEAKER_01: How does our psychiatric diagnostic manual,
31:40
SPEAKER_01: the DSM-5, handle stress as a trigger for psychiatric illness?
31:45
SPEAKER_00: Ah, this raises an important question.
31:47
SPEAKER_00: The DSM-5 dilemma.
31:49
SPEAKER_01: Right.
31:50
SPEAKER_01: Adolf Meier is a biopsychosocial model which says genes,
31:53
SPEAKER_01: environment, and stress all interact, dominates modern psychiatric thinking.
31:57
SPEAKER_01: But the DSM-5 does not emphasize this model.
32:00
SPEAKER_00: No.
32:01
SPEAKER_00: The DSM-5 is deliberately designed to be descriptive and atheoretical.
32:06
SPEAKER_00: It focuses on phenomenologic typology.
32:08
SPEAKER_01: It doesn't care why you are depressed.
32:10
SPEAKER_01: It just cares if you tick the symptom boxes for the required duration.
32:13
SPEAKER_00: Which creates massive clinical inconsistencies.
32:16
SPEAKER_00: According to the DSM-5,
32:18
SPEAKER_00: major depression is major depression,
32:20
SPEAKER_00: whether it appears after you lose your job,
32:22
SPEAKER_00: survive a war zone, or for absolutely no apparent environmental reason.
32:25
SPEAKER_01: Wait, I have to challenge that entirely.
32:27
SPEAKER_01: You're telling me the DSM-5 completely ignores why someone is depressed?
32:30
SPEAKER_01: That seems incredibly counterproductive.
32:32
SPEAKER_01: Yeah.
32:32
SPEAKER_01: I mean, if someone is deeply depressed,
32:34
SPEAKER_01: unable to sleep,
32:35
SPEAKER_01: and cannot get out of bed because their spouse just died in a sudden car crash,
32:39
SPEAKER_01: Isn't that a fundamentally different clinical entity than someone
32:42
SPEAKER_01: who develops severe melancholia out of nowhere
32:45
SPEAKER_01: while their life is going perfectly well?
32:47
SPEAKER_01: How does a clinician even work with a manual that ignores context?
32:52
SPEAKER_00: It is a profound debate in the field, absolutely.
32:55
SPEAKER_00: Historically, the DSM actually agreed with you.
32:57
SPEAKER_00: Until the DSM-5 was released in 2013, there was a bereavement exclusion.
33:02
SPEAKER_01: Okay, so it used to be different.
33:03
SPEAKER_00: Yes.
33:04
SPEAKER_00: But they removed that exclusion in DSM-5.
33:06
SPEAKER_00: Why?
33:21
SPEAKER_00: The reasoning was that severe grief can trigger a true major depressive episode
33:25
SPEAKER_00: that requires clinical intervention,
33:27
SPEAKER_00: and artificially denying the diagnosis based on
33:30
SPEAKER_00: an arbitrary two-month timeline prevents patients
33:33
SPEAKER_00: from receiving necessary treatment.
33:35
SPEAKER_01: Okay, I can see the logic there.
33:36
SPEAKER_00: However,
33:37
SPEAKER_00: it replaced the exclusion with a recommendation for clinicians
33:40
SPEAKER_00: to exercise clinical judgment.
33:43
SPEAKER_00: You must determine if the reaction is disproportionate or inappropriate to the stressor.
33:48
SPEAKER_01: Which is a welcome call for thoughtfulness,
33:50
SPEAKER_01: but it places a really heavy burden on the clinician to untangle normal,
33:55
SPEAKER_01: painful human adaptation from pathological distress.
34:00
SPEAKER_00: It requires the clinician to be an expert in the human condition, not just a symptom checklist.
34:04
SPEAKER_01: And it gets even more complicated when you look
34:07
SPEAKER_01: at how different psychiatric illnesses relate to stress.
34:11
SPEAKER_01: Let's take schizophrenia.
34:11
SPEAKER_01: We need to be very clear here.
34:13
SPEAKER_01: Stress does not cause schizophrenia.
34:15
SPEAKER_00: No, the etiology is deeply genetic and neurodevelopmental.
34:18
SPEAKER_01: Exactly.
34:19
SPEAKER_01: But stress plays a massive role in the course of the illness.
34:22
SPEAKER_00: Absolutely.
34:23
SPEAKER_00: The stress vulnerability model posits that the biological vulnerability renders
34:27
SPEAKER_00: the individual highly susceptible to the negative effects of even minor stressors.
34:32
SPEAKER_01: Right.
34:32
SPEAKER_00: The most striking clinical example is expressed emotion.
34:35
SPEAKER_01: Oh, this is fascinating.
34:36
SPEAKER_00: This is a research proxy for familial tumult,
34:39
SPEAKER_00: criticism,
34:40
SPEAKER_00: hostility, and emotional over-involvement in the patient's home environment.
34:44
SPEAKER_01: And the data on this is stark.
34:46
SPEAKER_01: Patients with schizophrenia who return to homes with high expressed emotion relapse
34:51
SPEAKER_01: at twice the rate of those returning to low expressed emotion environments.
34:55
SPEAKER_01: The social environment acts as a massive biological trigger.
34:58
SPEAKER_00: Moving from neurodevelopmental to affective disorders,
35:01
SPEAKER_00: we discussed the HPA overactivity and depression.
35:04
SPEAKER_00: The elevated CRH,
35:06
SPEAKER_00: ACTH and cortisol, and the failure of dexamethasone to suppress cortisol production.
35:11
SPEAKER_00: Chronic stress mirrors the neuroendocrine abnormalities of major depression.
35:15
SPEAKER_01: But here is where my assumptions were completely upended when reading this.
35:18
SPEAKER_01: We've established that chronic stress and major depression equal
35:22
SPEAKER_01: an overactive HPA axis and high cortisol.
35:25
SPEAKER_01: Yes.
35:25
SPEAKER_01: So logically,
35:26
SPEAKER_01: if we look at post-traumatic stress disorder,
35:28
SPEAKER_01: PTSD, which is triggered by horrific life-threatening trauma...
35:33
SPEAKER_01: That must equal astronomically high cortisol, right?
35:36
SPEAKER_01: If depression is high stress, PTSD must be maximum stress.
35:40
SPEAKER_00: That is exactly what early researchers assumed, and it is entirely incorrect.
35:44
SPEAKER_00: PTSD is uniquely characterized by hypocortisolism, abnormally low cortisol.
35:49
SPEAKER_01: Low cortisol.
35:50
SPEAKER_01: How is that even physically possible after a massive trauma?
35:53
SPEAKER_00: The neurobiological implications are still being elucidated,
35:57
SPEAKER_00: but it represents a profound dysregulation of the HPA axis in
36:00
SPEAKER_00: the opposite direction.
36:02
SPEAKER_00: It suggests enhanced negative feedback sensitivity.
36:05
SPEAKER_01: Back to the thermostat.
36:07
SPEAKER_00: Exactly.
36:07
SPEAKER_00: Remember our thermostat analogy.
36:09
SPEAKER_00: In PTSD, the thermostat becomes hypersensitive.
36:13
SPEAKER_00: Even a tiny amount of cortisol triggers the receptors to completely shut down
36:18
SPEAKER_00: the HPA axis,
36:19
SPEAKER_00: resulting in chronically low cortisol output despite high central levels of CR8.
36:24
SPEAKER_01: That just shatters the idea of a single universal stress response in psychiatry.
36:28
SPEAKER_01: You cannot just measure cortisol in blood and quantify stress.
36:31
SPEAKER_00: No, you can't.
36:32
SPEAKER_01: The neuroendocrine profile of PTSD is not akin to chronic stress,
36:36
SPEAKER_01: and it is not akin to major depression.
36:38
SPEAKER_01: The biological signature of trauma is incredibly heterogeneous.
36:42
SPEAKER_00: Which brings us to a vital clinical challenge.
36:45
SPEAKER_00: If the biological markers are so varied,
36:47
SPEAKER_00: how do clinicians actually quantify this invisible burden of stress in a patient?
36:51
SPEAKER_01: Well, we've evolved our measurement tools over the past century.
36:54
SPEAKER_01: It starts in the early 20th century with Adolf Meyer.
36:57
SPEAKER_01: He proposed a brilliantly simple tool called the Life Chart.
37:00
SPEAKER_00: The Life Chart, yes.
37:01
SPEAKER_01: The clinician literally plots the patient's life on a line from birth to present.
37:07
SPEAKER_01: You pencil in important life events on one side and map the onset or worsening
37:11
SPEAKER_01: of health problems on the other.
37:13
SPEAKER_01: It visually maps the chronological correlation between stress and illness.
37:17
SPEAKER_00: It remains a highly effective,
37:19
SPEAKER_00: elegant way to elicit a clinical history and spot recurrent patterns.
37:25
SPEAKER_00: But researchers wanted something more statistically quantifiable.
37:28
SPEAKER_01: Naturally.
37:29
SPEAKER_00: This led to the collaboration of Thomas Holmes and Richard Ray in the 1960s.
37:33
SPEAKER_00: They developed a checklist of about 40 life events and assigned them
37:37
SPEAKER_00: a specific number of life change units based on their severity.
37:40
SPEAKER_01: So the death of a spouse is at the top,
37:42
SPEAKER_01: a traffic ticket is at the bottom,
37:44
SPEAKER_01: you tally up your score to measure your stress exposure.
37:46
SPEAKER_00: But the key insight of the Holmes-Ross scale,
37:49
SPEAKER_00: and one that is often counterintuitive to patients,
37:52
SPEAKER_00: is that it tallies both negative and positive life events.
37:54
SPEAKER_01: Right.
37:55
SPEAKER_01: Getting married, getting a promotion, having a child, these all score points.
37:59
SPEAKER_01: Exactly.
37:59
SPEAKER_01: Why?
38:00
SPEAKER_01: Because the underlying assumption is that any major life change imposes a demand
38:04
SPEAKER_01: for adaptation, and that adaptational demand taxes the organism.
38:08
SPEAKER_00: Positive events are not biologically benign.
38:11
SPEAKER_00: They still require your HPA axis and sympathetic nervous system to adjust to a new equilibrium.
38:17
SPEAKER_01: However, the Holmes-Raw approach has major criticisms.
38:21
SPEAKER_01: Some argue that negative events carry far greater anguish and
38:24
SPEAKER_01: that universal waiting ignores individual idiosyncratic appraisal.
38:29
SPEAKER_00: Very true.
38:29
SPEAKER_01: But the most significant flaw common
38:31
SPEAKER_01: to all retrospective stress scales is retrospective distortion.
38:35
SPEAKER_00: Yes, patients forget.
38:37
SPEAKER_00: They deny.
38:37
SPEAKER_00: They repress.
38:38
SPEAKER_00: Or, conversely, a patient who is currently depressed might exhibit effort after meaning.
38:43
SPEAKER_01: Effort after meaning.
38:44
SPEAKER_00: Yes.
38:45
SPEAKER_00: They selectively recall negative events from the past to explain why they feel
38:48
SPEAKER_00: so terrible today, which artificially inflates their stress score.
38:52
SPEAKER_01: Ah, I see.
38:53
SPEAKER_01: To combat this, the modern clinical solution is Ecologic Momentary Assessment, or EMA.
38:59
SPEAKER_01: We use smartphones and apps to have patients record behavioral and biological data
39:03
SPEAKER_01: in real time.
39:04
SPEAKER_00: Fantastic.
39:04
SPEAKER_01: It captures the stressor,
39:05
SPEAKER_01: the context and the symptom exacerbation exactly as it happens,
39:09
SPEAKER_01: eliminating the retrospective bias and allowing us to graph the true daily impact
39:13
SPEAKER_01: of microstressors.
39:14
SPEAKER_00: Okay, so we have the framework,
39:16
SPEAKER_00: the mechanisms, the clinical manifestations, and the measurement tools.
39:21
SPEAKER_00: How do we actually treat it?
39:22
SPEAKER_00: Let's talk interventions,
39:23
SPEAKER_00: starting with pharmacology,
39:25
SPEAKER_00: specifically the use of anxiolytics like benzodiazepines.
39:29
SPEAKER_01: Oh, this is a hot topic.
39:31
SPEAKER_00: The field has historically oscillated on this because it is a profound double-edged sword.
39:37
SPEAKER_00: On one hand,
39:38
SPEAKER_00: prescribing benzodiazepines carries the obvious risk of physiological dependence
39:42
SPEAKER_00: and tolerance.
39:44
SPEAKER_00: Furthermore,
39:45
SPEAKER_00: some theorists argue that blunting the anxiety with a pill impairs the efficacy
39:49
SPEAKER_00: of psychotherapy.
39:51
SPEAKER_00: It offers a temporary chemical shield that prevents the patient from actually doing
39:55
SPEAKER_00: the hard work of developing internal coping skills.
39:57
SPEAKER_01: Right.
39:58
SPEAKER_01: If you take away the distress artificially, you remove the biological motivation to adapt.
40:03
SPEAKER_00: Exactly.
40:04
SPEAKER_00: On the other hand,
40:04
SPEAKER_00: depriving a patient of relief when they are in
40:06
SPEAKER_00: an acute severe crisis is clinically unconscionable.
40:10
SPEAKER_00: Short term use of low dose benzodiazepines can be extremely helpful
40:13
SPEAKER_00: to help patients survive an unusual,
40:15
SPEAKER_00: overwhelming stressor,
40:17
SPEAKER_00: provided it is done in association with supportive crisis psychotherapy.
40:22
SPEAKER_00: It is about bridging them to a place where their nervous system is calm enough
40:25
SPEAKER_00: to actually engage in psychological work.
40:27
SPEAKER_01: And that psychological work is primarily cognitive behavioral therapy or CBT.
40:32
SPEAKER_01: The stress and coping models developed by Richard Lazarus form the foundation of CBT
40:38
SPEAKER_01: for stress management.
40:39
SPEAKER_00: Lazarus breaks cognitive appraisal down into two distinct sequential steps, doesn't he?
40:44
SPEAKER_01: He does.
40:45
SPEAKER_01: The first is primary appraisal.
40:47
SPEAKER_01: This is the patient asking, what does this event mean?
40:49
SPEAKER_00: Okay, give me an example.
40:50
SPEAKER_01: If a patient is diagnosed with rheumatoid arthritis, they evaluate its significance.
40:54
SPEAKER_01: If they appraise it as a catastrophic loss,
40:56
SPEAKER_01: you know,
40:57
SPEAKER_01: I will never be able to do anything I care about again,
40:59
SPEAKER_01: they are guaranteed to become anxious and depressed and,
41:02
SPEAKER_01: as we know, spike their IL-6 and actively worsen the joint destruction.
41:06
SPEAKER_00: But if they appraise the exact same event as a challenge,
41:10
SPEAKER_00: saying this prevents some physical activities,
41:12
SPEAKER_00: but I can adapt,
41:13
SPEAKER_00: alter my lifestyle and find meaning in other things,
41:16
SPEAKER_00: the biological and emotional outcome is fundamentally different.
41:19
SPEAKER_01: Exactly.
41:20
SPEAKER_01: That primary appraisal, threat versus challenge.
41:23
SPEAKER_00: And the second step is secondary appraisal.
41:25
SPEAKER_00: This is the patient evaluating what can I do about it and will it work.
41:29
SPEAKER_01: It is an assessment of their own coping skills.
41:31
SPEAKER_00: Right.
41:32
SPEAKER_00: Do they have the repertoire of behaviors to manage the challenge?
41:35
SPEAKER_00: Yeah.
41:35
SPEAKER_00: And do they believe in their own self-efficacy?
41:38
SPEAKER_01: Now, CBT aims to make patients aware of these automatic split-second appraisals
41:42
SPEAKER_01: and actively change them.
41:44
SPEAKER_01: A highly specific way this is done is using a daily diary format.
41:48
SPEAKER_01: You teach the patient to track antecedents, behaviors, and consequences.
41:53
SPEAKER_01: The ABCs.
41:54
SPEAKER_00: Let's consider a minor traffic accident as an example.
41:56
SPEAKER_00: The patient was hit from behind at a stoplight.
41:58
SPEAKER_00: No damage to the car, just slight neck pain.
42:00
SPEAKER_00: That is the antecedent.
42:01
SPEAKER_01: Okay, so the patient's automatic thought is, this kind of thing always happens to me.
42:05
SPEAKER_01: My boss is really going to be angry at me for missing the morning meeting.
42:08
SPEAKER_01: The feelings are frustrated and anxious.
42:11
SPEAKER_00: And the physiologic consequence,
42:12
SPEAKER_00: the sympathetic activation, is clenching teeth and a churning stomach.
42:16
SPEAKER_01: Right.
42:18
SPEAKER_01: By writing this down, the patient engages in self-observation.
42:22
SPEAKER_01: They start to see the link between the antecedent event,
42:26
SPEAKER_01: their catastrophic cognitive appraisal, and the resulting physiological distress.
42:31
SPEAKER_00: This leads to cognitive restructuring.
42:33
SPEAKER_00: It highlights logic errors.
42:35
SPEAKER_00: Does this always happen?
42:37
SPEAKER_00: Is the boss definitely going to be angry?
42:39
SPEAKER_00: The patient learns to ask themselves, what is the evidence that this thought is true?
42:44
SPEAKER_00: Is there an alternative explanation?
42:46
SPEAKER_00: What is the worst outcome and what is the most realistic outcome?
42:48
SPEAKER_01: And they replace the negative thought with a rational response.
42:51
SPEAKER_01: If the thought is,
42:52
SPEAKER_01: I have no control over this situation,
42:55
SPEAKER_01: the structured rational response becomes,
42:57
SPEAKER_01: it's true, I can't change what happened, but I can control how I respond right now.
43:02
SPEAKER_00: It sounds deceptively simple,
43:04
SPEAKER_00: but practicing this actively alters the neural networks related to stress
43:07
SPEAKER_00: and coping.
43:08
SPEAKER_01: It physically changes the brain.
43:10
SPEAKER_01: And that brings us full circle to the isopraternal phenomenon we discussed at
43:14
SPEAKER_01: the very beginning.
43:16
SPEAKER_01: The cognitive act of meditation blocking the physiological effects of adrenaline?
43:21
SPEAKER_00: Exactly.
43:21
SPEAKER_00: Stress is not a simple pathogen.
43:23
SPEAKER_00: It is a mismatch between a stressor and an organism's adaptive capacity.
43:28
SPEAKER_00: It involves incredibly intricate crosstalk between
43:31
SPEAKER_00: the fast sympathetic nervous system,
43:34
SPEAKER_00: the slow HPA axis,
43:36
SPEAKER_00: the inflammatory cytokines of the immune system,
43:38
SPEAKER_00: and even the microbiome in your gut.
43:41
SPEAKER_01: It alters your DNA expression through epigenetic locks
43:44
SPEAKER_01: and accelerates cellular aging through telomere shortening.
43:47
SPEAKER_00: But through cognitive restructuring and behavioral adaptation,
43:50
SPEAKER_00: we can fundamentally alter how those biological systems respond.
43:54
SPEAKER_01: Which brings us to our learning reinforcement.
43:56
SPEAKER_01: Instead of just listing multiple choice options,
43:58
SPEAKER_01: let's test our clinical reasoning with a rapid-fire case review.
44:01
SPEAKER_00: Okay, I am going to throw clinical scenarios at you,
44:04
SPEAKER_00: and you walk me through the mechanisms we just discussed.
44:07
SPEAKER_01: Put me on the spot.
44:08
SPEAKER_01: Let's do it.
44:09
SPEAKER_00: Case one.
44:10
SPEAKER_00: Okay, the slow pathway.
44:26
SPEAKER_01: The psychological stressor is processed, and the hypothalamus releases CRH.
44:31
SPEAKER_01: That travels to the anterior pituitary, which releases ACTH.
44:35
SPEAKER_01: The ACTH circulates systemically down to the adrenal cortex,
44:39
SPEAKER_01: which pumps out cortisol, hypothalamus, pituitary, adrenal cortex.
44:43
SPEAKER_00: Spot on, case two.
44:44
SPEAKER_00: A patient is brought into the emergency department after a terrifying car crash.
44:48
SPEAKER_00: Their sympathetic nervous system is in extreme overdrive.
44:52
SPEAKER_00: How is that acute sympathetic activation generally influencing their immune system's
44:56
SPEAKER_00: response to pathogens in that exact moment?
44:58
SPEAKER_01: The fast pathway.
44:59
SPEAKER_01: Catecholamines are surging.
45:01
SPEAKER_01: That sympathetic activation is going to actively shunt immune cells,
45:04
SPEAKER_01: generally suppressing the cellular and innate immune responses,
45:08
SPEAKER_01: the ones necessary for fighting off intracellular viruses,
45:11
SPEAKER_01: while it spares or even enhances the humoral antibody-driven response
45:15
SPEAKER_01: to extracellular bacteria.
45:16
SPEAKER_00: Excellent.
45:17
SPEAKER_00: Case three.
45:18
SPEAKER_00: You are evaluating two different patients.
45:20
SPEAKER_00: Patient A has severe treatment-resistant major depressive disorder.
45:24
SPEAKER_00: Patient B has severe post-traumatic stress disorder following combat.
45:29
SPEAKER_00: If you look at their neuroendocrine profile,
45:31
SPEAKER_00: specifically their cortisol, what unexpected difference are you likely to find?
45:35
SPEAKER_01: Ah, the great paradox.
45:37
SPEAKER_01: Patient A with major depression will likely show HPA overactivity and hypercortisolism.
45:42
SPEAKER_01: But patient B with PTSD is frequently characterized by hypercortisolism,
45:47
SPEAKER_01: Abnormally low cortisol due to
45:49
SPEAKER_01: that hypersensitive negative feedback loop we discussed with the thermostat analogy.
45:53
SPEAKER_00: Precisely.
45:54
SPEAKER_00: Case four.
45:55
SPEAKER_00: Let's talk genetics.
45:56
SPEAKER_00: You're reviewing a patient's history of severe childhood maltreatment.
46:00
SPEAKER_00: Based on prospective studies like the New Zealand cohort,
46:03
SPEAKER_00: if this patient possesses a specific genetic vulnerability,
46:06
SPEAKER_00: they are vastly more likely to develop depression.
46:09
SPEAKER_00: What specific genetic marker are we looking at?
46:11
SPEAKER_01: That would be the promoter region of the serotonin transporter gene.
46:15
SPEAKER_01: Individuals who are homozygous for the short allele of that gene are highly vulnerable.
46:19
SPEAKER_01: But again,
46:19
SPEAKER_01: only when that genetic lock interacts with the environmental stress
46:22
SPEAKER_01: of childhood maltreatment.
46:23
SPEAKER_00: Yes, quite right.
46:24
SPEAKER_00: Case five.
46:26
SPEAKER_00: You are conducting CBT with a patient newly diagnosed with multiple sclerosis.
46:31
SPEAKER_00: They are highly distressed.
46:32
SPEAKER_00: According to Lazarus' model,
46:34
SPEAKER_00: the patient is currently evaluating what they can actually do about the illness and
46:38
SPEAKER_00: whether their coping skills will be effective.
46:40
SPEAKER_00: What is the clinical term for this specific evaluation?
46:43
SPEAKER_01: Assessing their own self-efficacy and coping resources is the secondary appraisal.
46:47
SPEAKER_01: The primary appraisal was them deciding if the MS was a threat or a challenge.
46:51
SPEAKER_01: Secondary is figuring out if they have the tools to handle it.
46:54
SPEAKER_00: Brilliant.
46:55
SPEAKER_00: Final case.
46:56
SPEAKER_00: A patient comes to you complaining of severe chronic sleep deprivation due to work stress.
47:01
SPEAKER_00: They report feeling constantly fatigued and aching.
47:04
SPEAKER_00: Given what we know about sickness behaviors,
47:06
SPEAKER_00: what specific immunological marker
47:08
SPEAKER_00: of inflammation is notably enhanced following their sleep deprivation?
47:12
SPEAKER_01: Sleep deprivation induces a state of systemic inflammation,
47:15
SPEAKER_01: specifically marked by enhanced expression of the pro-inflammatory cytokine IL-6.
47:20
SPEAKER_01: That IL-6 crosses the blood-brain barrier
47:23
SPEAKER_01: and induces those exact sickness behaviors,
47:25
SPEAKER_01: the fatigue and aching, even without a viral pathogen present.
47:29
SPEAKER_00: Excellent review of the clinical mechanisms.
47:31
SPEAKER_01: If you want to dive deeper into any of those specific pathways
47:34
SPEAKER_01: or visually map out these concepts,
47:36
SPEAKER_01: I highly direct you to read alongside the foundational texts on stress
47:40
SPEAKER_01: and psychiatry, specifically chapter 27.0 of Kaplan and Sawdok.
47:45
SPEAKER_00: You really need to view the clinical literature charts,
47:49
SPEAKER_00: particularly the Takotsubo echocardiogram showing that ballooned left ventricle
47:53
SPEAKER_00: and Adolf Meyers' original line drawing of the life chart.
47:57
SPEAKER_00: Visualizing the data makes the mechanism stick in your mind.
48:00
SPEAKER_01: It is essential reading for any clinician trying to fully grasp the breadth
48:04
SPEAKER_01: of how adversity gets under the skin and alters the body.
48:07
SPEAKER_00: Absolutely.
48:08
SPEAKER_01: And as we wrap up our time in the stress laboratory with Medlock Holmes,
48:12
SPEAKER_01: I want to leave you with a final provocative thought to mull over.
48:15
SPEAKER_01: We spend so much time in medicine and honestly in our daily lives trying to eliminate stress.
48:20
SPEAKER_01: We view it entirely as a hazard, a toxic presence we must eradicate.
48:24
SPEAKER_00: We do.
48:24
SPEAKER_01: But the Holmes-Ray scale taught us that positive life events,
48:28
SPEAKER_01: falling in love,
48:29
SPEAKER_01: getting a major promotion,
48:31
SPEAKER_01: having a much desired child,
48:32
SPEAKER_01: they provoke the exact same adaptational demands and neurochemical cascades as
48:37
SPEAKER_01: the negative ones.
48:38
SPEAKER_00: So true.
48:39
SPEAKER_01: So perhaps the goal of psychiatry shouldn't be the eradication of stress.
48:43
SPEAKER_01: Perhaps the goal is the mastering of our biological and psychological flexibility.
48:47
SPEAKER_01: If a patient's brain can literally block the effects of intravenous adrenaline just
48:51
SPEAKER_01: by engaging in the cognitive act of meditation,
48:54
SPEAKER_01: what other physiological destinies are you currently assuming are completely set
48:57
SPEAKER_01: in stone?