And then also skill deficits, which is often what behaviorists remediate. And it's obvious that a skill deficit in social ability, for example, isn't equivalent to a metabolic disorder. But let me start by asking you how you lay out your conceptualization of metabolic disorder and what implications you think that has for the diagnosis and further understanding and treatment of so-called mental disorders. You

know, it's a complicated situation, as you even just began to hint at. And, you know, maybe one easy way to outline my conceptualization is that there are mental states and there are mental disorders. So all humans will suffer. All humans will have anxiety at some point or another in their life. All humans will get depressed, or most humans will get depressed if they experience tragic loss or humiliation and shame. And those are not brain disorders, as far as I'm concerned. That is the normal state of being a human being. And as you alluded to, depending on your upbringing and your experiences, you might learn maladaptive themes or maladaptive lessons in life. People aren't trustworthy. You can't trust anybody, you go through life that way. And that can actually have very serious consequences for people. But I don't think those people have brain disorders. The reason they believe what they believe, the way that that happened is all obvious once you understand the person's full history. And so there are myriad ways in which humans can suffer and develop maladaptive patterns that do not include brain disorders. And psychotherapy can be helpful and just being human and all of the life skills that you talk about apply to those people. And yet there are other people who have brain disorders. Their brains are malfunctioning. They have anxiety or panic for no reason. They have crippling OCD for no clear reason. They have crippling, unrelenting depression for no clear reason. They have hallucinations, delusions, manic episodes, and other types of symptoms. And it is largely believed in the psychiatric field that these people do in fact have brain disorders and that their brains are malfunctioning. And at the end of the day, what I am arguing is that there is in fact a central theme to these malfunctioning brain symptoms. And they revolve around metabolism. And that if we take this global picture and understand that these brain conditions are actually metabolic in nature, number one, it can help us better understand how all of the risk factors can come together to result in mental disorders or mental illness. But much more importantly, it gives us clear, actionable treatment that we typically do not use today. And they span a wide variety of different treatment strategies, but they include things like changes in diet, changes in exercise, looking for hormone or vitamin deficiencies, thinking more kind of in a more sophisticated way about substance use, thinking in a much more sophisticated way about the medications that we prescribe for psychiatric conditions. Because some of them can improve brain metabolism, but we know that some of them are actually harmful to metabolism.

Let me outline a diagnostic approach to you with regards to the differential diagnosis of depression. And I've thought about this a lot. So tell me what you think. And then we'll turn to a discussion of the list of contributing factors to physiological brain dysfunction or illness. And we can tie those together. Okay, so one of the things I noticed as a clinician, and I think that this is key to solving the mystery of perhaps, perhaps, of differential response to serotonin reuptake inhibitors and other antidepressants. Now, I don't think it's the only key, but I think it's an important one. I don't think it's one that's been attended to enough. So I noticed in my practice that there were two broad classes of people with depression. Okay, so we could define depression first for everybody watching and listening. So depression looks like a condition analogous to an excess of pain. It's associated with grief and shame and guilt. It's characterized by a decrease in positive motivation, so less enthusiasm, less curiosity, less hope, often hopelessness per se, and a proliferation of negative emotion. negative emotion. And then that manifests itself, well, it can manifest itself as a virtual inability to move even, no motivation, and often an overwhelming sense of doom and a proclivity even towards suicide. So that's the depressive realm. It's a psychogenic pain condition, and it differs from anxiety, even in its, although they overlap. I had clients who were in that condition, but then imagine that those broke into two classes. I have the odd client who, by all appearances, by all standards of multidimensional assessment, had fine lives. So these would be people who were reasonably healthy, apart from the depression, let's say, who had a functioning marriage, who had friends that they liked, and a marriage that they liked, even though the depression might have been twisting their perception of that. So, for example, they may have thought that they were now so useless and contemptible that no one like their wife could possibly love them, and that they were, know, a burden to their family. But they still had tight family relationships. They often had careers that were well-developed and going fine. They were about as educated as you could expect. They didn't necessarily have any substance use disorders. They did productive things outside of work, but they were profoundly depressed. Okay, so that's one category. Now, the other category of person wasn't like that at all. They had no relationships. They had no stable marriage. They had no friends. They had no job. Their educational history was fragmented at best. They had no plan for the future. They didn't have a life. Now, both of them were miserable and maybe even in an equivalent manner. But the first group of people with a functional life was very much unlike the second group. Now, what I noticed, and I've never found any literature directly pertaining to this, maybe you know of some, I found in my practice that if I recommended to those clients, the ones who had a functional life, that they tried antidepressant, it was often likely to have relatively miraculous effects. Whereas the people in the second category, the antidepressant, could maybe help ameliorate the worst of their suicidal ideation and possibly tilt them a little bit more in the direction of positive motivation, but generally speaking, not a very effective treatment. Now, and logically, because if all those things were absent, the mere offering of a biochemical treatment wasn't going to, you know, provide someone with no partner with a highly functional marriage. So, and I think in that differentiation, we can also see a distinction between the biological, and that would be what was hypothetically plaguing the people with functional lives, and the conceptual, because it was the absence of the ability to go about forming all those relationships, say, and pursue all those pathways in the latter case. So the first thing I'd like to ask you is for your general thoughts about that diagnostic approach to distinguishing between the biological and the so-called psychological, and then how you go about doing that, because you already pointed out that you accept the distinction between biological mental illness, let's say, and conceptual disarray, something like that, or lack of skills.

job of articulating that framework that I just outlined, that there are some people who have brain disorders. Their brains are doing things that don't make sense. They don't make common sense. The first person that you described or that first category of people you described, it doesn't make sense that that person's depressed. They've got a good life. Everything's going well for them. And they will often even say that. They will say, I don't know what's wrong with me, doctor. I don't know what's wrong with me. My wife loves me. My kids love me. I have a good job. We finally saved up enough money to get that vacation home that we wanted. I just got a promotion at work. By all intents and purposes, I should be happy, and I am miserable, and I feel like a burden, and I don't know what's wrong with me. Please help me. I would argue that person has very likely has a brain disorder. The pathways that are hardwired in the brain to trigger the depression response are malfunctioning. They are misfiring. They are causing the sensations and all of the experiences and perceptions of depression when they shouldn't be. And here's an easy analogy. So there's, you know, all humans will experience pain. Pain is a normal human experience. If we injure ourselves, we will feel pain. If we get surgery, we may have prolonged and extensive pain. Those are not disorders. They cause suffering, and people often want help for that, and people often want treatment. They might even take pills for it, or they might need physical therapy or something else. treat pain, but they don't have a pain disorder. And then there are other people who have pain disorders. Their pain system is malfunctioning and causing the sensation of pain when there's no clear good reason for pain. So that gives us a framework of normal and extreme, like if you get surgery, you may have extreme pain, but those aren't disorders. And then somebody who's got a pain disorder, where they have chronic, unrelenting pain for no good reason. Their pain system is malfunctioning. And so that first category of person, I would say their brain, the networks that cause all of the different experiences of depression, those networks are malfunctioning. They are either overactive or underactive, depending on what symptoms we're looking at, but they've got a malfunctioning brain that is causing the experience of depression. The second category that you mentioned, the person whose life is just a tragic mess. They've never had anything good going for them. They don't know how to create a good life. They don't know how to take care of themselves, how to have good, positive relationships. Maybe they have no purpose in life. Those people will, in fact, experience depression. And if they don't experience depression, that in and of itself is a disorder. Anybody in that circumstance should, in fact, be depressed.