Welcome to the Psychofarm podcast. This podcast is for education and entertainment. It certainly is not medical or psychiatric advice, diagnosis, or treatment. Listening does not create a doctor-patient relationship with me or Dr. Fu. If you're a patient, certainly don't change your treatment plan because of something you hear in the show. If you're a clinician, do not use this podcast as a clinical reference or substitute for your own training, judgment, thinking, and up-to-date sources.
Opinions are our own and don't necessarily reflect any employer or affiliated organization and may even be detached from reality. Good morning, John.
Good morning, Greg.
Today we have Dr. White with us. Dr. White, would you mind introducing yourself?
Yeah, I'm an assistant professor at Texas Tech on their Amarillo campus, and I do a lot of inpatient psychiatry in the morning and some outpatient in the afternoon. And I'm the co-corkship director, so I'm with students all the time, and I love psychiatry.
Awesome. And the reason why I'm super excited to have you on here is you've been doing a Substack on affective neuroscience. And I feel like you've been crushing talking about a severe blind spot that psychiatry has. And I'm hoping today we're rolling out a new format. We're pretending you have an hour to get your ideas out there. The biggest impact you possibly can make in an hour.
That's my challenge for you today.
Okay, I'll do my best. And I think how I would start that is, what if I were to tell you that there's 60 years of bench neuroscience in multiple mammals, and every animal that's been studied, it all points to the same thing, that there are conserved homologous circuits responsible for affective impulses, And this is through direct stimulation, lesion studies, neurochemical studies, and that this is well replicated, and that this seems to be responsible for motivating emotional behavior.
And that psychiatry hasn't really thought about it or incorporated this at all into how we think about pathology.
And do you believe even just a superficial understanding of this can help people understand and treat patients?
Yeah, absolutely. I think even having a better understanding of emotional experiences and kind of what's driving us and the idea that this is something that's in every mammal that's been studied and it's going to magically not be in it. These systems are deeply subcortical, so brainstem, midbrain, and these studies are very difficult to do in humans. We cannot just go wapping into human brainstems and do these kinds of experiments.
The work was foundationally done in animals, and so it didn't get really any attention clinically. But the more you use careful correlations in human studies where you find it and build on that, And yeah, I would say how can anyone who's working with patients not want a better understanding of what's moving them, of what's building those emotional experiences, what's responsible for a lot of the big arousals, the big, big feelings that we have.
I'm super excited to hear you kind of go off on this stuff. And I'll give a little bit of disclaimer in terms of my familiarity with this stuff. I first came across Jokpeng Sepp, who I think you'll get into in a second, who's the forefather of Apex. I came through his work through Nancy McWilliams because she was talking about the primary emotions. And I was like, oh, I should probably...
As a psychiatrist, you'd think I know a little bit more about emotions. I almost never talk about them in my years of residency. So I bought his book and I was like blown away of like, wait, we pretend... That biological psychiatry is taking over. And here is this like tome of all the biological correlates that we know about. Why is all this stuff being ignored? It's almost like, wait, wait, wait.
Why do the therapists know more about the biology than psychiatrists who are biological? It just didn't make any sense.
No, I mean, yeah, it's mind-blowing. I mean, I had the same reaction. You know, it was actually, Greg, one of your videos I saw as a resident that first led me to discover Jacques Ponskepp's work. And I had the same reaction. My mind was blown. I was like, how have I never heard of this through all of And I think there's a bit of an answer. When DSM-3 was coming out in the 80s, there was a lot of concern.
There were some studies showing psychopaths. And so, you know, a big concern was, you know, getting things down to reliability and checklists and emotions were felt to be unimaginable. Empirical, right? Just qualia. And so it was not a priority. And you can see that in the DSM. There's not a lot to do with emotions. How many times do you have a patient with a chief complaint of anger?
There's literally very few places in the DSM that mention anger. And you can repeat this with all those primary emotions. So no, it is mind-blowing. It's absolutely foundational for how we develop. And it's foundational for loss of pathology.
So we don't bury the lead here. I want to talk about some of the things that I think you're helping to shine some light on. Things that you're helping to answer is how do I talk to patients when they don't fit into a neat DSM box? There's so many patients where it's like, yeah, you're having problems. Let's call it generalized anxiety disorder, give you Zoloft. It kind of works.
We're not really talking about the real problem, but we can both put our blinders on and pretend that it's just this categorical thing. Another thing is how to explain to, you know, for example, borderline personality disorder patients that some problem they're having isn't necessarily a DSM problem or a medication fixable problem. And how to talk to them without saying like, hey, it's your personality that's broken. The patients will have personality problems that don't fit into the DSM boxes that we have.
And there are patients that are saying, oh, it's just your personality. It doesn't help the person. It's neither insightful nor helpful. And I think... I've seen in your Substack, you're starting to shine some light into how we actually can answer those questions.
Yeah, absolutely. I fully agree. There are so many patients out there that they have a lot of the problems that you would think of with borderline personality disorders, like someone who has really difficulty controlling their anger, but they've never overdosed. They've never cut themselves. They They have stable relationships, yet they struggle and they seek care. And so all these patients that struggle with these big feelings, and if you're formulating a patient by trying to fit them into a categorical process, You guys were talking about this before.
And so, you're affecting people's identity, and you're not really giving them as valid an understanding of how they are. How their own systems are working. And so I've noticed that and that part of how I've continued to build in the space and believe in it so much is I work with patients on it. I explain how broad strokes, What affect is and how affect impairs our thinking when it comes on real strong.
If someone is having big, big feels and really strong affective arousals, the emotional regulation literature is pretty clear. More activated the subcortical systems are, and the cortical systems are less activated, and the inverse is true. Okay, so people that struggle with big, big feels and do things that they regret or do things that they wouldn't otherwise normally do, And I'm really going to tell them that there's something wrong with their personality, that it's a trait based problem, because a lot of times everything is fine until it's not.
And patients really appreciate kind of slowing down and having that understanding of their own affect. My personality is disordered. I don't need to modify the content of my primary affective experiences. I don't need to change when I feel fear or feel grief or feel suffering. I'm trying to help them build that capacity to observe these things and not be forced to act on them. That's what these systems were evolved to do.
They were evolved to have very strong, quick outputs of very conserved behavioral responses. No thinking required. I think most of us can relate to that. I think almost anyone who's read a book about anything literature-wise, red-hot anger, white-hot rage, kind of the tragic consequences of humanity, of the things we do when we're emotional, from Romeo and Juliet to nearly anything else. I think it's something people can relate to, the idea that we're not thinking clearly when emotional.
Mm-hmm.
Now, I would love for you to kind of start us off. Before we jump into things, what is your Substack name?
Affect before diagnosis. Awesome.
So now walk us through, you mentioned you talked to patients about what is affect. Can you give us an idea of what is affect? How do you explain it to patients? How do you think about it?
So I literally get out a pen and paper, and I draw a really shitty version of a brain, and I divide it into brainstem, midbrain, into cortex. And I explain, we all have a brainstem, if you look at a A cat brainstem, a dog brainstem, a human brainstem, a whale brainstem. You don't see a lot of big differences, okay? This is the part of your brain that controls your heartbeat.
Do you have to think about your heart beating? Most people say no. Occasionally someone says, yes, you got to adjust fire a little bit. I'll just move on up. This is the midbrain. This is where affect comes from. These are where your ancestral inheritance, these are where your emotional experiences, this is where this information comes up. And as we move up, there's a primacy on the influence of information.
And so your heart beating is going to take precedence over anything else. The emotional signals that come up, they take precedence over what comes next. So I kind of draw a picture. I talk to them about their emotions and the big feelings they're having. And then this is your cortex. This is mostly blank from birth. This is what you grow across your development. So the feelings that you have, These are very responsible, your early experiences.
So most of the patients I'm talking about this, these are usually people that have had pretty difficult, adverse experiences. People that have these big emotions and these kinds of consequences, certainly if we're on the inpatient unit, these are people who can usually relate and usually will agree, yes, I'm someone who has intense experiences. If I line up 10 people, And I flick them all behind the ear.
You know, I'm going to get 10 responses from, you know, someone might ignore that. Someone might turn around and try and hit me. Okay. And almost all of these, you know, patients invariably can be like, yes, you know, I think I do respond to things pretty intensely compared to others around me. And in essence, uh, we'll just look crazy. You know, if person A is responding to the same stimulus at one out of 10, that person B is responding at 10 out of 10, your person B just looks crazy.
But, uh, You know, does that mean they have a personality disorder or a problem with their traits? Maybe, you know, some people fit that borderline construct pretty well. And so I, you know, I draw a picture and I walk them through it slowly and I get them to be thinking about, you know, the relationship between their planning, their thinking and the feelings. I make it very clear, you know, you know, ask you, Greg, when was the last time you planned on a feeling?
I don't think it's ever happened. It just pops out of nowhere.
Yeah, perfect. Yeah, exactly. We don't plan on feelings. They really come and go. There's not a lot of really control you have over the flow of your feelings. If someone says, just get up, feel better, let's go to a movie, you can't just make yourself feel something differently. Okay. And so people spend a lot of time trying to control their feelings. People spend a lot of energy, you know, trying to control something that's really not controllable, getting stuck on those feelings.
And of course, if you have a baseline, a more reactive, you know, affective systems and you're feeling things more intensely, you are going to struggle with this more. You're going to struggle growing the cortical capacity needed to, I hate using the word regulate, but the cortical capacity to observe your internal experiences, to reappraise, to modulate, to slow down, to put a delay between impulse and what you're doing.
Think about these things, right? Yeah. So, you know, with that, I'll tell, you know, I first started thinking about this because I do a lot of geriatric work and, you know, I'll have so many patients come to me and they'll have been diagnosed with depression or anxiety and they'll have, you know, no past psychiatric history whatsoever. And I'll just be like, oh, you know, we're developing an episodic mood disorder in our, you know, ripe old age that we never had.
That never made sense to me, right? We've never been anxious before, but now we're, you know, diagnosed with GAD. And what I would notice is that really, if I would do cognitive testing, I know psychologists out there would be insulted that I call the MOCA cognitive testing, but I think it's good enough. They usually have impairments on them. They're usually not, you know, they don't have dementia.
They might not be severe, but they're usually people that are having new psychiatric problems in older age. You know, they'll have deficits. And, you know, when I started thinking about it is, you know, that core You spend your whole life growing to help you handle these impulses, these experiences, these affects. It's degrading, especially for cortical dementias. So your subcortical systems are firing just fine. So the panic, grief, the separation, the stress signal, the rage, fear, all those things that have been firing across your life and you've got the brain to handle it, it's As your cortex is receding and losing neurons, you are no longer modulating that affect properly.
So they're responding to those signals where before they would have been able to feel that just fine. So that's the why now. And oftentimes I see those patients and families struggle because they get put on treatments and... You know, sometimes, you know, our meds have effects, they have effect sizes, but these are usually progressive problems. And so really slowing down and explaining what's going on and why it's not, oh, you have depression, that's why you feel bad now.
You have anxiety. That's why you feel bad now. But this is what's the process that's going on. It helps patients. It helps families understand better. It helps them engage with the problem differently. You know, the lady that first made me think of this, the family, they described that she had just, everything was more or less fine. They would visit her, but when they leave, she would throw a temper tantrum and she would just cry and wail.
And that sometimes she would follow them out and just jump on the hood of the car. And that, but otherwise she could, no, no serious problems, uh, you know, no, no real psych history, uh, you know, not, not anything else the family could tell. And they're just like, what is going on? Right. And so, you know, that's, uh, you know, we haven't really gotten into the systems, but one of them, one of the most important for psychiatry is panic grief.
Okay. It was very important when, when mammals evolved, uh, you needed a way to make, make it feel bad if you were separated
from your caregiver.
Okay. Reptiles don't really need that, right? You lay your egg, you leave it alone. Okay. You know, when you start doing more complex stuff, nature needed a system to say, you're separated. This needs to feel bad. You need motivation to go reattach. You need to go get that. And so, you know, humans have that. Has there been a study? Have we gone and done the same studies in animals?
We've done those in humans. No. Does anyone really think our midbrains and brainstems are going to be that different? And so what I'm watching in this patient is she's having that separation distress. Their family's visiting. The family's leaving. That's normal. That should fire. It should feel bad. And if she, you know, wasn't having, you know, cognitive impairment, she would be able to, you know, modulate that. She'd modulated her whole life.
She'd, you know, she never threw tincture traumas before. And so you're kind of seeing these systems when you start looking more into affective neuroscience and thinking about it, seeing it, and you see these systems in real time with your patients. You know, I've just found it too compelling to ignore. And it just, you know, I can't help but write about it and just, you know, scream from the rooftops like, hey, we got to think about how we incorporate this into psychiatry.
pharm. All right, back to the show. Now, what I really love about what you've been saying so far is it can be simplified an extent that anyone can understand it while also being backed with really heavy basic science. Now, you say cortical and subcortical, and sometimes it's like, that can feel a little too complicated, but it's as simple as, let's call it, there's essentially, you mentioned three brains, but we can even go to, let's say mammalian and subcortical.
And then like the new human part of the brain. And what you're saying is that affect emotions are generated from the animal brain. And then the thoughts, the cognitions are just gently modulating these emotions to the best of their ability. And that's our new brain. Yeah, yeah. So correct me if there's anything I don't know.
I would agree with that. I would just say you're underselling just how fantastic the human cortex is. So by gently modulating, I mean, that's one way to put it, Greg. Obviously, I think about everything we've done with our brains and our cortexes compared to other animals. So maybe a cat is gently modulating. They have enough cortex to gently modulate. I'm not going to eat my baby today.
Okay. You know, it made me mad. But I think we have so much capacity for reappraisal, modulating, acting on cortically represented values rather than these ancient animal brain impulses.
Mm-hmm. And that's helpful in that I guess a better way to put it is that we have variable degrees of ability to modulate depending on tons of different circumstances. And I see exactly what you're describing. There's so many patients that I see them labeled as personality disorder or something. They have an anger issue. They're actually their entire life is highly functional. But then when they get triggered with anger, they cause massive problems.
And then they're remorseful. They regret it. They wish they didn't do it. They go like, I'm a different person. I actually I'm not acting in my values.
Or I'm so depressed.
Yeah, I did it all the time. And this is a way of formulating it. It's not that the whole system of personality is broken. It's this one thing that's causing much bigger problems than it needs to. And then they're constantly kind of making up for it. So I love how this is capturing a lot of different problems that we don't really have vocabulary other than these categories that don't quite fit.
No, not at all. And, you know, to build on that, I mean, you can see some fully functioning adult human, I mean, I say fully functioning adult human, so people that really do meet criteria for borderline persona disorder, I think of it as they do not have the cortical capacity to modulate, to appraise, to handle those intense affective arousals, right? Every patient I meet that has severe borderline persona disorder, they're pretty much fine until they're not.
Like, literally, they'll You know, I overdosed yesterday and crashed my car. I'm fine now. How was yesterday? Right? The affect has died down. And they have, you know, really no concept. And so I would say that's someone just like the, you know, on the road today. You know, I currently, I'm not able to, you know, functionally, you know, handle my own affective arousals, right? Usually, what do we see in these patients, Greg?
We're pretty disrupted, invalidating childhoods, sometimes severe trauma. And so not a lot of, you know, they weren't being taught psychological skills. They weren't engaged in a project of, hey, let's grow your cortex. This is going to be great, right? They were like barely surviving childhood. And so then we see they're entering adulthood and they don't have, you know, they really don't have the cortexes needed to handle, you know, what developed underneath.
You know, and we can shrink it back even further. Okay, well, you ever hang out with toddlers? Oh, yeah. Nieces and nephews. Nieces and nephews, great. Yeah. I mean, you know, you have a toddler that have a temper tantrum. You ever have any luck getting them to calm down just by talking to them? No, no, no, no. Absolutely not. No. Yeah.
Shout out, Henry.
No, not at all. Cortex is still growing. We don't consider it pathology. They are slaves to their affective systems. The subcortical animal brain that's ready from birth, that's born, they are growing their cortex. Okay. And so when you take away their toy, they are the embodiment of sadness and grief. When they get angry, they are in the embodiment of rage. When the mom leaves the room and they start crying, they don't have the neuronal connections to remember, oh, mom will be back.
Oh, you know, I can, you know, I can handle this. None of that's there. It's nothing but the, they're stuck in rage mode until the affect dies down. And so you can kind of trace just to kind of the general principle of just our affect and the cortical capacity to regulate. And I think of those things as living, breathing, dynamic relationship. And the good news is Instead of telling someone, hey, you have a personality disorder, sucks to suck, you can say this is one way to think about your problem.
And the good news is calibration can change. You can engage in the process. That's essentially what, I don't know, is it fair to say that's what DBT is in some ways?
Ian, actually, I was going to talk about DBT because a lot of, I remember, so I taught a DBT group and we were going over opposite action. And one of the lessons we were doing was kind of like mapping out your emotions, mapping out what happens when you have those emotions, mapping out how long those emotions last. And I remember being, this is so basic. Why is this revolutionary to me?
This is things I probably did when I was in kindergarten. Why am I not getting it again until third year of residency in regards to actually thinking about the way that emotions can, they have a half-life, they have a certain characterization to them. Why am I thinking about this for the first time at 33? Yeah.
Yeah, why are we teaching grade schoolers math, right? Why do we not? For sure. Something you hit on there, that emotion piece, that is just so diverse. So many things go into when those affective arousals hit all the time. Our whole life trajectories influence that. Shame, just take, that's going to be so different if you're born in Japan than if you're born in England. So even the word, what we're calling emotions, just carries so much weight and so much baggage.
Depending on your own memories, your own narratives, your culture, everything you've gone through. And so really the emotions and working with emotions is one thing. And I think psychology does that better than psychiatry. But considering that affect, that subcortical valence, the neurophysiologic arousal that has primary influence that the midbrain is sending up, that the animal brain is sending up.
Could you talk a little bit about, so when you say affect, how is that different from emotion? What are the core emotions? Do you have any like pearls that things that you often teach about the emotions or little things that you see related to psychopathology that aren't commonly thought of with regards to the primary affects?
So Ponchkepp was able to identify seven what he would call primary process affective systems. Okay, so these were the ones he had enough evidence for to put forward saying, hey, in the animal research I've done, these are distinct, think of them as distinct circuits. Okay. And so a lot of this, he would, you know, electrically stimulate, you know, very small areas, get a, you know, behavioral output.
And then, you know, they would then move the stimulation up, you know, a nanometer, move it up and move it this way, move it that way. And if they continued to get that behavior output, Substack, Substack, Substack, Substack, Psychofarm. And so the positive valence, that means if it's a positive valence, animals like it. If they're given the opportunity, they stimulate it themselves. They're on electrodes. They don't have any aversion to it.
So that's the seeking system, the loss system, the care system, and the play system. And then there's three negative valence systems. And so these are systems that animals have aversion to. They have very, very negative valence. It clearly does not look like they like it. It does not feel good. And they will actively work to terminate this kind of stimulation. That's fear, rage, and panic grief. And kind of like we talked about, that panic grief is really...
Slang for separation distress. We have this system, it's supposed to feel bad if you get separated from your primary attachment. So a rat gets separated from the mom, it's going to have that panic grief activation. He added that people would hear panic and they'd think panic attacks, so he added grief to it.
Now, how are these seven things different from emotions?
Okay. So yeah, so the affect would be that raw subcortical valence, the arousal that's being sent up. So that animal part of the brain, the midbrain, it's sending up, when these circuits are activated, they're sending up their information, their arousal. So that's either that positive valence or And that's what's coming up. And I would say an emotion is kind of that experience once, you know, shaped by cortical appraisal, memory, narrative, culture, identity, right?
So if you kind of said that, but, you know, shame is going to look very different in Japan than in, you know, America or England or other places. So the affect themselves, I'm thinking of it as this just emotion. Powerful, raw valence. And emotions are kind of the rich language, everything we have a human history for. All our rich poetry, music, literature, the things we talk about when we feel things.
I would call that that is affect that has been shaped through our brains. And that is, people use the terms interchangeably. I try not to. The DSM certainly has no concept of distinguishing between the two.
What are things that you've found that related to affective neuroscience that you provide with regards to psychoeducation or little interventions that you do even in like medication management?
Oh, yeah. So kind of like we were talking about earlier when I, you know, literally kind of draw the brain and show this direction of influence and kind of trying to get them in touch with if they struggle with, you know, intense affective experiences and, you know, behavior dysfunction and problems in life. So beyond that, I think counseling on medication is really important. And so when I prescribe a medication for this kind of problem, I want to make it very clear.
This isn't, oh, you have anxiety, take a medication, or oh, you're depressed, take a medication. I go over, what are the effects of this medication generally? So take an SSRI. I'll be like, this medication can affect emotions in a very broad way. And people experience this differently. So it's pretty well known. Yeah. I explain, I say, this emotion might make you feel 8 out of 10 anger, not 10 out of 10 anger.
I don't know. You'll have to tell me what you feel. This might be a good effect. If you have one less big fight with your partner a week where you yell at your kids less, this might be a good medication for you. But if you punch a window, if you get above a 6 out of 10, Taking a medication that makes you an out of 10, not 10 out of 10 might not mean much for you, especially if you're having side effects.
So I try and paint it in a broad brush. I try and bring up emotional blunting. I hear a lot of patients, especially if you get into the, I think the more borderline or the more severe end of it, that because they're so prone to feeling things so intensely, they're very prone to reporting the emotional blunting. They're the ones that are going to notice. Hey, I turned on Gilmore Girls.
I did not feel the butterflies in my stomach. What the fuck did this medication do to me? This is what the medication does. Here are all the effects of the medication on sexual functioning, on your GI tract. We can talk about some other effects. You can get some neuroplasticity. You can go into all these things with them and say, this is the thing the medication does. Do you think this is something that's going to be useful in your life?
Do you think it's something that's going to help you? If you think so, we can try it. And you'll have to tell me. You're the expert on how you feel. You'll have to tell me if it's something that's helpful for you or not. Mm-hmm. And that's going to be different with every patient. And that's a very different than if I think someone is in, you know, someone is actually depressed in an episode.
I'll, you know, I'm not going to go into all that. This is antidepressant.
Now I'm imagining, I'm just going to give an example. Let's say, let's use anger as one. So let's say I'm a patient who has a lot of anger. You draw your pictures. And then I feel like my next question would be like, all right, doc, how do I, how do I strengthen the top down stuff? And how do I decrease the bottom up stuff?
Oh my, yeah. So, you know, I don't think we're there yet for decreasing the bottom-up stuff. That seems to get set pretty early from early experiences. And then again, because this is one of those things, because psychiatry doesn't recognize affective neuroscience, we don't actually study these things. So, you know, I couldn't really say much about it. So I think where most of our treatments are, are strengthening our top-down control.
So that's a project of psychotherapy. And so people who have these kinds of affective problems that aren't fitting into these, you know, DSM category diseases, that's a, you know, I try and get them, you know, I'm a one trick pony with acceptance commitment therapy. So I'll do a bit of that, but I'll try and get people engaged in psychotherapy. So intentionally, You guys talk on your show a lot about practicing mindfulness.
So absolutely, I'm taking people through mindfulness, contacting the present moment. I think that's absolutely step one, the ability to come to the present moment. You're not going to observe any information. If you don't wax on, wax off every day when it's boring, you're not just going to randomly contact the Right. So really getting patients to, you know, engage in some of these psychological skills, you know, especially if they're taking the medication, right?
If you're taking a medication that makes emotions a little, you know, less intense, you know, increases your neuroplasticity a bit, right? That's ripe for combining that with psychological skills. I think every psychiatrist knows that no matter what we're calling it or how we're framing it.
So you mentioned, you know, your one trick pony with acceptance and commitment therapy. Do you have any little little teachings or little things that are particularly helpful for patients that you can do in medication management that are, you know, it's not the therapy proper, but like ways of conceptualizing things or psychological tools in the sense that that help patients?
Uh, so yeah, so yeah, literally guiding them through, you know, uh, mindfulness practice and, and contacting the present moment, uh, you know, helping them practice observing internal experiences, uh, you know, teaching them to name, you know, you know, name and, and, I don't practice therapy in a sense because I see people for 20 minutes. I do medication management. I'm a psychiatrist. But I'm trying to cram in, in addition to pairing these medications, I'm trying to pair in ACT processes and skills and point people and be very clear, this is not therapy.
You need to engage in actual psychotherapy. So I think that the pearls would be you absolutely cannot help your patients if they don't know what the problem is and if they don't get engaged in the right kind of treatment. So someone who has these affective problems and they're using the language of, oh, I'm just so depressed or, oh, my ADHD or I'm just anxious, whatever, and they think just taking a medicine, I'm trying to build insight that that's not going to make their problem go away.
Because really, I don't think there's any evidence for a lot for decreasing the intensity of the bottom up. And that's why there's so many people that struggle with this. That stuff gets set pretty early in life. There's not a lot you can do to change your brainstem. And so really, cortical capacity, that's what therapy is. Grow those neurons, baby. Grow, baby, grow. Tell people, they never stop growing.
I mean, there's plenty of evidence for that. Neural networks grow by addition. Extinction really is growing new inhibitory connections. So it's all about growth. We don't delete old memories. We don't delete things. You just grow new ones. One thing I think helping patients have that understanding that they have a brain that works this way, that they can grow, that they're not done growing. You know, I think if you don't have, if patients don't have a capacity of understanding of their own brain and their own processes, they're really going to struggle with working on problems that, you know, I hate to say rooted in personality.
I mean, rooted in affect, which a lot
of people will call
personality.
Now, we talked a little bit about using top-down control to mitigate bottom-up raw affects. It's actually funny. I feel like reading acceptance and commitment therapy, I actually started thinking about thoughts, like the contents of thoughts are meaning. I now think of thoughts as like a phenomenological byproduct of cognitive processes. And the... The whole purpose of thoughts is to have thoughts that calm things down, that contextualize, and that there's almost no truth to them.
It's been helpful. The actual thoughts in my head are nonsense. It's almost like breathing. I can have a little bit of control to sometimes guide those thoughts in ways that calm things down. But the actual thoughts are 99% are nonsense, not true. And it's actually very helpful of thinking it is like, oh, the thoughts that I choose, the only really, not the only purpose, obviously, but one of the main purposes is I can use those to temper down those, as you say, big feels.
And thinking of it less as a personal thing, like those thoughts are me and my expressions of the truth and more as like, oh, thoughts can be just a tool that can help or hurt me in certain situations.
No, I love it. Love it, Greg. Absolutely. I mean, you know, I asked you earlier, have you ever planned on a feeling? I mean, you can say the same thing. Have you ever planned on having a thought? I mean, it's pretty much the same thing. They're just there. They come and go. You know, we give them meaning, right? You have to, you know, engage in it and...
If you deconstruct it at that language level, like you're talking about, what is it really? And how much power people are giving these things that are constructs that are coming and going that we don't have a lot of control of the flow to flow of the thoughts in our head. I mean, like you mentioned, you can do your best to shift a little bit and try and focus on what you want.
But if your mom died yesterday, good luck trying to think of something else.
Now, sharp transition from what you just said. I've seen you write a little bit about frustration with regards to, you know, quote unquote, treatment resistant depression or quote unquote, treatment resistant anxiety. And I think you talk about how like patients aren't, it's not that they're failing treatments. It's like the entire framework is broken or incorrect or not working. Could you elaborate a little bit more on your thoughts on that?
Yeah. So first I'll preface by saying that like, you know, every patient is different, but I have a, you know, really high threshold. If someone is not doing well on antidepressants to say that they have treatment resistant depression. I would much rather reformulate the patient. I would much rather make sure we're doing the work on affect or personality. And I rarely see someone that is struggling with what would be called treatment risk of depression who had their life squared away, who's getting good sleep, who's eating whole food, who's not sedentary, who's exercising, who has connections.
My goal was to help people be connected to what's important to them. And, you know, people who are connected to what's important to them rarely, you know, find their way in the hospital, rarely find their way in a psychiatry office. And so I see a lot of those patients who are, you know, aimless, leading relatively aimless lives, putting a lot of faith in medication. You know, people who want them to try the next thing.
It's almost like they prefer this kind of external struggle. Like, you know, as long as I have this quest out here, keep trying to get the medication right, you know, they can stay engaged with that battle just fine. But you've asked them, what would you do if you felt better? What if this medication worked and everything changed and you felt differently? What would be different about your life?
What would you do differently? And if someone can't answer that very well, I don't see the utility in futile prescribing. Especially if those other things aren't addressed. And when you only have a 20-minute appointment and we've been reduced to just prescribing medications, a lot of people just continue to get prescribed multiple, multiple medications. And not that people enjoy that, but I think can be problematic.
I think you say it's not that people enjoy it, but it's what they know, I think is kind of what I expected you to say. It's what they've come to expect from psychiatry. It's like they come to the appointment, they tell you, I'm not doing so great. The doctor goes, have you tried... You try something new, works a little bit, then you get worse, you come back.
And they're kind of stuck in this cycle. And it's a failing of our frameworks and psychiatry. There's so many patients that they come with treatment-resistant depression. I'm sure the previous psychiatrists have in their chart a personality disorder or some other conceptualization, but it's never communicated to the patient. It's like they never had a chance of getting better.
Yeah, I agree. We do a terrible job communicating these things to patients. And that's a big part of the problem. And I think that's a big part of the frustration among clinicians. Telling someone they have a personality disorder is about the most invalidating thing you can do. Right. I mean, it's it's it's it's frankly insulting. And, you know, a lot of patients aren't going to engage in that.
They're going to go somewhere else. They're going to you know, it's it's a heavy ass. And so it makes it hard to build a strong therapeutic alliance. And I think that's actually part of why I think defining a lot of this pathology, a lot of the psychopathology around personality as problems of affect and regulation, as subcortical affect and cortical regulatory capacity. I was too young to operate under that system to deal with these things in a way that they could understand and that they actually engage in.
The patients I do this kind of thing with, I get a lot of good feedback on it. I think everybody loves having a better understanding of how their organism, how these things work and they can engage in it better.
One thing, so you have a paper published, I forget in which journal. You've talked to us so far about the seven primary affects. And in the paper, you talk about how there's also four dimensions that they vary. It uses very fancy terms, but we can make them very simple terms. You said that there's baseline tonic activity, phasic reactivity, recovery kinetics, and threshold sensitivity. Fancy terms. What I'm hearing is for each affect, there's an amount that when you're just chilling, there's an amount when it gets activated.
There's an amount of time that it takes to burn off. And then how much stimulus do you need to kind of get set off? So if we're talking about anger, baseline, most people have relatively low anger. Then there's an amount of anger that people get when they get triggered. There's a certain amount that triggers them. And then there's a length of time that it lasts once they're triggered.
It's funny. I thought of the affects in regards to those four parameters. And it captures so many things. There's so many patients that they describe all these problems in their life. And I can't quite make sense of it because in the appointment, it's like, you're such a nice, sweet guy. What do you mean that you're freaking out? And screaming with your partner and all these things. I feel like you've heard like emotion is energy and motion or something.
These affective systems bring up different parts and we've become different people. And how someone responds to anger, they can look like a totally different person. And it can last for a very long time. It's very different and very individual. I wish that one thing people did more was reflect on their seven primary emotions and think about what is their blueprints.
Uh, I'm glad you said that because I, you know, uh, for one, I actually just, I just kind of made that up. I have no, I have no evidence for that. I just kind of assumed there have to be kind of variables and those things based on, you know, many, many things. Uh, so I'm glad you say that, but I've never thought about, I've never explained in that much depth to a patient.
I've never Yeah, absolutely. That's interesting to think about. I'll probably play around with that with patients. Maybe I'll come up with a worksheet or something. I think anyone listening or patients anywhere, we're going to be able to see this and see this in our own lives with everyone we know and just clearly see how different people respond to the same kind of event and just see such differences.
I do want to hear more about You've written a little bit about the evidence. I think I read something about decortication. Could you talk a little bit about that?
Oh, yeah. Love to. I think this is one of the funnest parts of diving into affective neuroscience. We can't do these studies in humans. No one is going to go decorticate a human. Okay. And so we really have to look very carefully at the evidence that Penchkep, you know, his program accomplished, and instead of ignoring it, think, how are we going to apply this? If we think that, you know, humans, you know, evolution, homologous And so, in 1928, Bard demonstrated, they called it sham rage, but it wasn't really sham rage, it was real rage.
They decorticated a cat, right? So they would just slice off the cortex of these cats, sew them back in. And what they noticed is these animals that have been decorticated respond to neutral or trivial stimuli with extremely exaggerated reactions. Okay, so they were just very labile. You know, the implication there, you know, Again, you don't need a cortex to have those, you know, what we would observe as emotional responses, emotional behaviors.
So these cats would arch their backs, you know, they would hiss, they'd claw the cage until they bleed. They're, you know, very, very, And then the neat thing in humans is this guy Merker in 2007 put together a case series of children born with hydroncephaly. Okay, so these are kids that are pretty much born without a cortex. And then he went around and documented things from caregivers and caregiver report.
And these children, spoiler alert, animals actually do pretty well without a cortex relative. Humans don't. We don't really thrive. So I don't think any of these people really live past a year. They don't do well. But for the time that they were alive, they displayed very similar exaggerated emotional responses. These children cried. They responded to comfort. And so they had these, again, these emotional behaviors and clear, you know, able to, you know, put what we would call distinct motor outputs in response to things.
And clearly, you know, the caregivers reported like, of course, my baby knows when I'm comforting them versus what. When they're crying and sad. And so he, you know, put together, you know, enough, pretty compelling that, you know, that same kind of premise, you know, these weren't humans who were intentionally decorticated, but these are humans more without a cortex and you can kind of see the same thing, right?
And so really, you know, when you get into this kind of stuff and you go further and further, it's just kind of like, why would we think this wouldn't apply to us? You have the same thing with cortical stimulation. Okay. A hundred years of cortical stimulation studies. Okay. Cortical stimulation, you can make people's arms move, you know, do all these things. What you don't get ever is any kind of emotional response.
Okay. That's just, that's been borne out in cortical stimulation for awake surgeries and same thing in animals even, but in humans. And then with deep brain stimulation, you get emotional responses. Okay. So, so, you know, DBS is, Sometimes they put it in the wrong place. Sometimes they go too far. You can get, you know, you can get suitable for crying. You can get mirthful laughter. So you get these emotional responses when you stimulate very low down and you get basically no emotion.
So I would say that's, again, more evidence that these circuits are there, they're responsible for these primary arousals, and I'm just basically giving you the 1% of the surface of this.
You know what this is making me think of? You're talking about stimulation. So TMS is stimulating the DLPFC, dorsolateral prefrontal cortex, and it helps with depression. Now, the DLPFC helps you focus, helps keep information in mind. It's kind of making sense. Yeah, absolutely.
I think TMS, I mean, it's got to be the future. I mean, that kind of work and extending it because, yes, it makes sense. It doesn't have to be, you know, TMS doesn't go deep enough to hit subcortical structures, but the That speaks to the relationship between the cortex or the fancy human part of the brain and these emotional systems. And it just speaks to the ongoing dynamic relationship and that strengthening that top-down system.
What's the bottom up? What's the sub-cortex sending up? What's the cortex sending down? And how are those things? That's happening all the time, 24-7. All those parameters you talk about. The cortex has millions of more parameters. What's the strength of what's being sent down? What's the intensity of that? What is its baseline kinetic? What are its recoveries? So there's got to be so many things that by, like you say, you're just forcing those neurons to activate, depolarize baby, right?
I mean, there's got to be, I don't have the evidence to say what exactly is going on, but it has biological possibility and makes sense intuitively for why that's helpful for depression.
Ian, this is a random little thing. I think of religion as like the, for a lot of people, it's like the best cortical controlling narrative you can have in your brain
that you send down.
And that's why religion helps a lot of people. But that's a story for another day.
No, I love when you said that. It's so true. In one of your episodes, you mentioned that, right? You're just like, oh, I love when my patients are religious. This is great. I know they're going
to do better. They have a better cortical, what do we want to call it, module that they can unlock and that they can send down to their brain. It's just a very helpful little thing. You can think whether or not it's true is completely irrelevant. It helps calm things down.
I agree. Yeah, I'm with you there.
Now, I'm paying attention to the time. Is there anything else you wanted to talk about?
Yeah, I think the last thing I'd hit on, I just I like telling the story of a pepper taunt and rage just to kind of, you know, hopefully highlight to anybody out there thinking about this kind of stuff, like what psychiatry is lost by not engaging with this So, it's approved for nausea for chemotherapy. But in animal models and in the, you know, Ponchkev's work in the brain, in NK1, one of the things it's very responsible for is rage arousal.
And so, you know, you can, you know, Stimulate these areas and get attack behavior. Okay. And you can, you give them the epipitant and it, uh, I butcher that word, but whatever. And you, you, you block it, you block NK1, you stimulate, you don't get it. So once those things, there's been knockout studies. Yeah.
Okay.
And so there were studies in the 90s where they took this drug, they took Epiprotant, and they tried to apply it to patients with major depressive disorder. And they tried to measure it using a HAMD. And so, you know, there was this excitement and Merck made this announcement and they're like, we're going to have a breakthrough in depression because of some of the initial, you know, you know, the tales all this time, you get an open label thing, it's promising.
You go to the studies and they They wash out. And so this was tried. It failed. They tried again. They tried it again with augmentation. And then there was a review in 2017, certainly 20 years after all this. And they were like, you know, why this failed even though it shouldn't Because it should work. And nowhere once in any of those studies in the review and anything was rage mentioned anywhere.
Nowhere once was anything about what the animal literature, what the brain science shows about what the NK1 system is for. And so, you know, that's what, you know, when you have a DSM and we aren't kind of thinking about some of the more valid, you know, affective experiences, it's costing us in terms of how we study, so how patients understand their problems. How we design trials, how we research these things.
And so, you know, I can't say that, you know, studying this drug for rage would have an effect. I don't know. But I can say, certainly, if you're looking at everything, there's no reason to think it would have an effect on depression. And there's no reason you would design a study to look at a HamD. You would want to do something Where you would look at how angry people get and see if the drug that is responsible for calming rage in every animal that they've studied in does anything to rage in a human.
That's the study I would want to see.
Yeah, this is interesting. It's making me think patients having variable response to medications. When you have a bucket as big as depression, as big as anxiety, there's going to be 20% are going to have major rage problems. 80% won't have major rage problems. As you said, it washes out because, you know, it is actually working for some. And when the bucket's too big, it's too heterogeneous. It's all going to look like it's not going to be helpful.
And there's so many little nuggets like that when you read the affective neuroscience literature. It almost feels like it's like, oh, I didn't realize that all this stuff was actually well spelled out. I thought we were way behind in regards to understanding the biological underpinnings of all this stuff.
Yeah, no, absolutely. Anyone who gets into the space, it is one of the most rewarding, fun things to read about. I'd recommend anyone go read Ponchkep's books. He's got multiple. There's just all the nuggets, as you call them, all the things that if you're a clinician, you just will just start clicking, clicking away. It's very fun to discover and read about.
Yeah. All right. I think we're if you have one more thing, I'll let you go. But I think we got to wrap up in time. Anything else you want to sign off on?
No, no, no. You know, just drop a conspiratorial line. You know, who knows why this stuff is ignored or not thought about? I don't know. Big questions. But no, that's it. That's all I got.
What's your theory?
You know, I just think it's too big. I just think the weight of inertia, like, you know, we've built all these systems on top-down observations for, you know, more than 100 years. And it would just be a pain in the ass to go back and be like, okay, how do we rethink about all these things? And just so people, I think that's why you don't get a lot of engagement.
The people who, you know, in charge of nosology have no interest. If you've had, you know, decades of a career invested in one thing, you have no interest in being like, oh, let's think about this differently.
Absolutely. Well, thank you so much for your time. This is awesome. I want to see some comments asking for you to be on it again so we can have you on again soon. Can you plug your Substack to sign us off?
Yeah, no, thanks for having me. This was great. You know, it's kind of a, you know, meet your hero moment. I've been a big fan of your work and your educational content. Students, residents everywhere. You know, it's good. Affect before diagnosis is where I write my stub stack pieces. You know, so come take a look. Thanks for having me. It's been great. Yeah, I appreciate it. I'll be honest with you.