The Best Depression Treatment For You

Quinn: [00:00:00] You know you're stressed. You know you're anxious. Do you have depression? And do you really need to know the latest in the biology of how the brain works and depression works or doesn't work and whether the gut is involved to get meaningful help? That's today's big question. I promise it's kind of one question, even if there's a ton of different answers, and they're going to be different for everybody.

And this conversation is a follow up to our last couple conversations about the brain and the gut and depression. My returning guest is Srijan Sen. Srijan is still the Francis and Kenneth Eisenberg Professor of Depression and Neurosciences at the University of Michigan and the Director of the Francis and Kenneth Eisenberg and Family Depression Center.

His leading research focuses on the interactions between genes and the environment, and their effect on stress and anxiety [00:01:00] and depression. And let's stop here. Before we get into it, our usual disclaimer folks, when we're talking about depression, and stress, and anxiety, and mental health, and suicide.

This is a very important conversation. It's an important one to be had, but if any of this could be triggering to you, please just skip over the next one, where we talk about oceans, or animals, or whatever. Nothing in this conversation, of course, should be taken as medical advice. If a treatment, or some combination of treatments, prescribed or recommended, by your health care provider is working for you, huzzah. That's great. Stay with it. Your personal experience with the treatment is much more relevant than anything in this conversation. If you're using a depression medication or other therapy and not getting relief from your depression symptoms, talk with your health care provider. And finally, of course, if you are struggling and feeling distress, or that you might hurt yourself.

You can text or call the Suicide and Crisis [00:02:00] Lifeline at 988, that's 9 8 8, right now, to get help. And you can even call and press 3 to speak to a counselor with the Trevor Project, our friends at the non profit who provide wonderful support for LGBTQ plus folks.

Welcome to Important Not Important. My name is Quinn Emmett and this is science for people who really give a shit.

In these weekly conversations, I take a deep dive with an incredible human, like Srijan, who's working truly on the front lines of the future, where there's so many questions and so much possibility, in an effort to build a radically better today and tomorrow for everyone. Our mission is to understand and help them unfuck the future.

Our goal is to help you answer the question, what can I do?

Quinn: Srijan, welcome back to the show. Welcome back.

Srijan Sen: Thanks for having me. Glad to be back.

Quinn: You are welcome, man. I'm so [00:03:00] glad it's starting to get a little warmer there for you.

Srijan Sen: 70 degrees yesterday, which is amazing for the beginning of March.

Quinn: Now I don't want to dive into climate stuff cause it makes me want to have another mental health conversation.

But from what I understand, like not a bad winter there?

Srijan Sen: No. The little known upsides of climate change are seen in Ann Arbor in January and February, but yes it wasn't a bad winter.

Quinn: I have made this like semi gallows humor joke a few times. Maybe not to you, but you know, it's very easy to be with people, friends, family, whoever.

But really, like, children, who so innocently, I am in down in Virginia. And it's very mild anyways. Like we get hot sticky summers, but it's not Alabama. We get cold winters, but it's not central New York where I lived. But you know, it's very easy for someone in December, January to be like, wow, what a nice day.

Can you believe it? And I'm just like, don't say it. Like, don't ruin this for them. They don't want [00:04:00] to talk about it right now. They don't want to know right now. You don't want to talk about it right now. But at the same time, it's like the most important thing we can do, but I'm like, can we just take a day off, bud?

Srijan Sen: Yes. I agree. Sorry. Sorry for bringing it there.

Quinn: No, it's fine. Like I asked the question, but it is, it's one of those things where, you know, again you want people to feel like, Oh, this is weather. So interesting. Isn't it wonderful? And we're not freezing. Like I get it, man. I lived in central New York for five years.

Like, Holy cow. It's relentless. You get a warm winter. Great. It’d just be superb if they weren't all going to be warmer than this one, basically.

Srijan Sen: Yeah. Yeah. So, but you know, it was a warm winter, but yeah, hard to do any, you know, snow activities like skiing or sledding. There was so little snow. But it's getting into spring and that's always a really nice time of year around here.

Quinn: We’ll take it. What's your spring sport? I know fall is football. Anything you're latched on to?

Srijan Sen: Getting nice enough to play basketball outside, which is nice, so I was just, you know, [00:05:00] playing with my seven year old and people in the neighborhood and stuff so it's fun and then I like to run and transitioning from the treadmill to running in the parks now the last couple weeks, which is nice.

Quinn: Real talk. How long until your seven year old can start to make some inroads on your game?

Like how long until you've got to actually start putting in work to keep up because I'm way past that basically with my 11 year old. I still talk shit, but it's not, if I had to stand up, it wouldn't be great.

Srijan Sen: I haven't figured out in basketball, still a little ways, but we were placing sort of, bets on the running part and like, when he's gonna beat me in like a 5k and you know, sort of over under of like four years, it looks like. Definitely, in like, you know, throwing football around. There's like short area quickness that he's like, just blows by me, but then, you know, I can still, I could still go faster than him in, you know, longer distances, but that the time is ticking for that.

Quinn: The stop, start stuff. I always like, I see [00:06:00] some of the things they do on fields and I'm like, my groin would just pull right off the bone if I tried to do something like that, or my knees would dissolve like at the end of Avengers. Yeah, same thing.

Srijan Sen: I have to warm up a lot now, like longer than I'd actually run.

Quinn: A hundred percent, the number of like, roll out devices and things I have, this is all connected to mental health folks believe me, because if I don't do this I lose it.

But anyways, it's definitely like the days are coming. I get it, yes, it's not great.

Srijan Sen: It's not great. But it's, yeah, it's fun to see the kids.

Quinn: It's fun to see, I do anticipate a day where I will be challenged, and I will have to decide if I'm gonna, like, leave my body on the field to win this one last, whatever it is.

And what the repercussions of that are, you know? Or if I just let them finally have it. I don't know. I don't know.

Srijan Sen: No. That's a glorious way to go out.

Quinn: Right? That's it. All right. So thank you for coming back. The last episode was meaningful to me and I got a lot out of it. And I think a lot of folks got a lot out of it because a lot of folks are dealing with [00:07:00] not just their own situations, but seeing it in their friends and their family.

Young people all over the place, older people all over the place, and it can be caused by any number of things, even if it's not depression, there is anxiety, there's all kinds of different flavors of this. I've certainly got my own versions of it.

Srijan Sen: Yeah, I really enjoyed the discussion and thought about points you made afterwards and heard from other people, so it was a really great discussion.

Quinn: Well,that's kind of you.

My children don't think about anything I say to them, so that's great. I say it and their eyes glaze over like a shark.

Srijan Sen: It'll come back to them in 20 years. They're going to be like that thing dad said to me.

Quinn: Right, sitting in therapy for themselves. I think what was immediately evident to both of us was, oh we can do 10 more of these, but in a slightly more specific version, which I'm excited to do, because obviously you are working on this every day where I'm just reading books and making up ideas.

Just to set the tone a little bit. So as we discussed a little bit more broadly in the first conversation, it is fortunately and unfortunately quite the moment for mental health, right? I've been trying [00:08:00] to think about the right way to frame this without it being way off base. Because again, like moronic liberal arts major here, but it seems like, more people are suffering than have ever actually been really reported before, and for a wide variety of reasons.

Now, part of that, again, sort of analogies like, is there an element of that's like cancer, where we have so much more earlier detection? Is there less stigma? So we're, I mean, not no stigma, certainly, but where we're talking about it more, especially men talking about it more. But there's obviously all these other reasons.

More people are suffering. We've seen how mental health for young people has gone downhill since phones, basically 2012, and COVID and all of these things, climate anxiety. But along those lines, we also know more than, getting like pros and cons here. It seems like we know more than we've ever known about the environmental, which you have dove into the genetic and other biological reasons and chemical influences on mental health.

But [00:09:00] again, as we've talked about before, and I did another conversation about the brain and the gut axis and how we're pulling those things apart, we're trying to knowing more means understanding, we really don't know what to know, or as much as we think, which is exciting and also unnerving depending on who's listening or reading the headlines.

Right? So, before we get going, I do want to do one thing, which is you're so thoughtful about all this. So I think you'll understand. Like climate change, obviously, as Katherine Hayhoe says, it's important that we talk about this more and more, right? But it's also important how we talk about it.

I'm trying to keep in mind like who is listening to this. So many people dealing with these things. So as we try to get more men to speak up and share their journey, or at least to be supportive, to seek help, especially with friendships going down. I saw some research in The Conversation from like 2022.

And they said, although viewing depression as a biological disorder may seem like it would reduce [00:10:00] stigma, in fact, research has shown the opposite, and also that people who believe their own depression is due to a chemical imbalance are more pessimistic about their chances of recovery. So I just want to take a moment and let's talk about how we talk about this.

Like how do we, and why do we have to be so careful about how we talk about the biological and chemical and environmental underpinnings of depression and anxiety? Does that make sense?

Srijan Sen: Yeah. Yeah. I think it's important to think about how we talk about it and do it in a thoughtful way that, that helps people.

I think it's important to stick to, as scientists, I feel like our role is to try to get to the truth. And so I think that's important. And then finding the right way to discuss it but discussing it in a truthful, straightforward way is important rather than trying to, I think, especially as psychiatrists, sometimes we get caught up in framing it in different ways, that might come across better.

And we're really bad at predicting how, what framing is going to work and what isn't, at least I am. [00:11:00] So I think being honest about what we know and what we don't know sets us up well to to have people feel part of the process of understanding that helps them and empowers them to help others.

I think the other point that might be related is, depression and anxiety and mental health is a little different than cancer and other things we've talked about in that how much we think about it probably affects it in ways that, you know, that is not true for cancer. And I don't think we know the answers here but there is probably, you know, anecdotally I’ve seen friends, patients, myself, sometimes ruminating about depression.

Talking about it more internally, to a lesser extent externally, can make it worse. And some of the best, different people or different situations are different, but certainly sometimes the best thing to do is to go out and do something. Go socialize, [00:12:00] go for a run and that will help your mental health more than thinking about it for another hour.

But figuring out what the right balance is of how much to think about it, how much to talk about it and not is fuzzy and probably different from situation to situation.

Quinn: Thank you for that. And I know we hadn't really talked about that side of it, but I really appreciate it. I thought about it this morning like, you know, I know children who are dealing with a lot of mental health stuff, which is heartbreaking because you're just like you barely understand anything at this point, much less your emotions, or how do you explain the chemicals, actually, it's not chemicals, but scientists are arguing that it might be, it's like, I thought about, you know, how during COVID, you know, I don't say post COVID.

We're still very late COVID. There's so many people still dealing with it and we'll deal with it, but in that first two years, how we basically did science live, right? And all the pros and cons [00:13:00] of that and what that has meant in the aftermath now, and how that really screwed with people in a lot of ways if they weren't ready to handle it, but also a lot of the scientists weren't ready to, you know, they didn't train for media training or anything like that.

They just happened to have a Twitter account and they woke up and they're like, I have 400, 000 followers. Like I have to be careful. And that's, you can be really careful and still look up six months later and be like, okay, it turns out like hand washing really actually didn't really do much for this specific thing.

But if you don't want norovirus, please use soap and water. You know, it's hard to do it live. And it's hard to, I imagine on your side, from a research perspective, as a practicing psychiatrist, like to think about again for each person, like we were saying with like, do I tell them the winter's warm because of climate change?

Like, how do you constantly readjust doing this live knowing that again, and we'll get into it., like everyone is arguing again over the serotonin theory and whether those SSRIs are even doing anything or if they would do something for someone else, but not you. Like, [00:14:00] how do you constantly. deal with, I guess, this just changing landscape when you're talking to people?

Srijan Sen: It's a challenge and I'm glad you brought up COVID and I think that's a good example and doing it in real time. I think scientists got in trouble or went wrong or we went wrong in science, from both political directions in trying to frame things to get people to behave in ways we wanted rather than just explaining the facts as we knew it at the time with the caveat that, that this is changing day to day, and we might think something differently and also got really attached to the theories that we came up with on, you know, whatever it is, March 5th, 2020. And then we have a lot more data 3 months later, but still sticking to, and that's a problem we have in science and broadly.

And I think that applies to serotonin things and all other parts of science. So trying to be open to [00:15:00] changing minds and changing directions if new evidence comes that way. And then also being honest on what we know without trying to think about how that will affect, you know, patients behaviors on whether they take a medication or not.

And not trying to frame things cause we're not that smart and really bad at predicting how people will take things. So, yeah, so I think that's at least how I approach it. And there's pros and cons to that. And I think it is really relevant to how we approach depression because still what, and depression treatments, it's still what we don't know vastly outweighs what we do know. So as you mentioned, we know a good amount and more than we did 20 years ago. But everything we find uncovers 10 other things that we don't know. And probably when we look back on, you know, in 2050 at this conversation, 2024, a lot [00:16:00] of what I say is going to sound really silly.

So being humble and knowing that, setting things up in ways that account for that I think is important.

Quinn: I appreciate that. I think, you know, that candid informed humility, like objective informed, like humility that everything is going to keep changing is helpful both to look at like our moment in time again, like it's easy to have this retrospective about the first half of COVID at least and go like, look at everything we did wrong.

We could have done better. It's like, maybe, yeah, there were definitely some good actors and definitely some bad actors. And so many people caught in between. And, it's almost, they're going to murder me, but it's almost as if climate scientists have it easy because as much as like, weather impacts have been getting crazy and the temperatures have been going up in various places in the ocean, is like a boiling pot of water.

It's actually basically followed the exact predictions of the model so far, which it won't always pros and cons, but they go like, no, this is what we said, which must be nice. Right? That's [00:17:00] not really the way the serotonin theory has gone so far. Let's dig into this. Cause it's been a little bit and I think it's really interesting.

So I want to offer my first caveat in the sense that again, we need to talk about this more. I can't, I don't even remember our first conversation was late last year, something like that. I had some just enormous stressors in my life, still do, things like that. So I started Prozac for the first time. And then, actually eventually doubled it cause it wasn't doing the job. I found this incredible psychiatrist who's been very helpful, very much in my face about things, which is the way it should, which is what I've always looked for. I've had just listeners, which is great for some people. I need someone who's like, gonna call me on my bullshit pretty daily, because that's really helpful.

He was like, your narrative is great. None of that is applicable here, buddy. Nice try. It's really great. So we're doing the Prozac, but I've also got and correct me where I'm wrong here again, because I was a religion major, but it's Klonopin, Klonazepam, what are they the same thing?

I don't know.

Srijan Sen: They're the same. Yeah. Generic and like brand name.

Quinn: Good talk. Anyways, I've got a package [00:18:00] of 50 of them. Little dissolvable guys. It goes under the tongue when I need them, when my children ask too many questions, when I think about all the open loops in my life. And it was a long time before I really thought like, okay, I think my exercise, as much as it's clearly helpful, and my meditation, is like not actually cutting it at this point.

Cause there's just too much. And it's been helpful. The thing I described to him was, listen, I tried to use like a really practical example, knowing that like, again, you don't get rid of anxiety. You don't get rid of stress. You don't want to. But I said in the mornings when I'm getting my kids ready, they usually come down full of joy, excited to see me, all these things.

And then I generally, basically ruin it for them by telling them to clean up their dishes and all this stuff and I get increasingly stressed I said, I'm definitely like a four to five out of ten most mornings and I was like I don't get this time with them back. That is an unacceptable range to me. Tell me [00:19:00] whatever it is I have to do to get to six or seven. No one's looking for eight here, like that's father of the year territory, and I'm not going to get it. And he was like, okay, well, let's double, make sure you're doing your exercise and not feeling bad. you're taking time to do that. Do this thing. So he's like, but let's also try these pharmaceuticals because who knows, but you've never done it.

And it could just, again, give you a little nudge and maybe help you sleep better, which can increase the whole thing, et cetera, et cetera. So anyways, that has been my journey so far. Again, it's not perfect, but it's been really helpful.

Srijan Sen: This isn't your point, but for our research studies. And so I've been doing it too.

Like we ask people to like rate their mood on a scale of one to 10 each day. And I find that really helpful in like, at least identifying for myself when I'm in a three or four mood. And when I'm in a six to seven mood, I've yet to get to like nine or 10.

Quinn: It's like, what are you, transcendent? Like, good luck.

Yeah, I had, you know, I've been doing the Apple watch things where they're like, Hey, how's it going today? And all that. And I'm always just like, ah, but hopefully it's a little less like that. Again, I [00:20:00] can't change what I do, I mean, I guess I could, I can't change that. I have three kids and I wouldn't change that either or stop their questions.

Cause one day they will stop asking me questions. I don't want that either, but how do I, if the only way out is through, like, how do I make the through a little easier? So how do I be a better self, partner, husband, dad, all that stuff. So anyways.

Srijan Sen: With patients it's, we've been able to see much more like when they're doing daily mood, like, you see four weeks after they start their Prozac, there is an uptick in their mood.

They go for more four days to more six days, or for some people there's not. It's much easier to cast that than trying to think back, like, what was my mood like in December? And is it better now? Like, we're really bad at doing that. So, I'm an advocate of trying to keep track on some kind of numerical scale, so that we can tell, and then like, oh, you know, things got, you know, something, you know, I started a new job and seeing if things are better or worse or you know, [00:21:00] things like that.

So, so I'm glad that you and your psychiatrist are talking about it in that way.

Quinn: Yeah. I mean, the retrospective stuff just never cuts it. Right. We're humans. I don't remember what I had for breakfast much less like how I was feeling yesterday. Other than like, I don't know, I'd probably discount it and be like, it was probably a five when maybe I had some six times.

So I don't know. So let's talk about what has been going on here on the pharmacological side. So, 2022. This sort of, I don't know if you'd call it a meta study, study of studies, claims depression is probably not only caused by at least this chemical imbalance in the brain. And the quote from the Nature piece is, the main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression.

And no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Of course, this is interesting for a variety of reasons, but also because SSRIs are designed to at least raise serotonin levels, right? Shortly after, 36 other researchers criticized those findings, [00:22:00] saying there were methodological weaknesses in the review process, selective reporting of data, oversimplification, and errors in the interpretation of neuropsychopharmacological findings.

That's all great. I hope they work it out for everyone's benefit, but on the user end, it comes down to this. And again, correct me if I'm wrong, which is, it seems like SSRIs work for some folks, some for really well, others, not at all or not so much. We aren't a hundred percent sure why or why not, ignoring the other treatments and things we can do.

What is the latest with serotonin theory, what does that mean for treatments now and going forward?

Srijan Sen: I'm peripherally involved in some of the controversies and discussions and had conversations with authors of that meta analysis and, or umbrella review as they called it. And there are like 10 different aspects and angles to it.

For me, one of the most important is that how we as doctors and [00:23:00] patients decide on a treatment should not be related very closely or I think at all to the mechanism of, the biological mechanism of how it works, even outside of the mental health and the brain and things we understand pretty well.

You know, why we use statins to reduce the risk of heart attacks and strokes is not because we know exactly what molecule the statins are interacting with and how that results. We know definitely, we know more about that than we know about SSRIs. But the reason is that in clinical trials, it's been shown to reduce heart attacks.

Quinn: The hopeful outcome is there and there's, you know, there were enough trials and clearly enough people are on statins in the world to know that like the side effects, whatever they may be are not adverse enough to keep it off the shelf.

Srijan Sen: Right. Right. And the same for you know, chemotherapeutic drugs, and it's not based on, like, we have this incredibly cool mechanism.

[00:24:00] The trials show that it doesn't actually, you know, reduce the cancer, but, like, we like the mechanism. Like, that's not how medicine should work. And hopefully it doesn't. And so the reason we use SSRIs and other depression and anxiety and antipsychotic drugs is because of the clinical trials which weren't at all involved in this umbrella review.

The clinical trials show as you discussed that SSRIs help reduce depression, anxiety in, not in all patients and not nearly in as many as we'd want, but work better than placebo in the overall assessment of studies. They don't work that much better than placebo.

Placebo works for a good number of people and SSRIs work a little bit better than them. And as we've all, you know, seen and heard, there's a lot of people who don't respond well to Prozac and Zoloft and the other SSRIs, but some people do and they should continue to take them. So I think the authors I take issue with them conflating [00:25:00] the research onto the biological mechanisms on to whether people should take the drug or not. I think the authors of that and I and others, no one disputes I think that exercising a lot or exercising the right amount, exercising better than not exercising, is good for mental health or sleeping eight hours a night is good for mental health. We have no idea about the biological mechanism of how, you know, going for a bike ride improves your, we don't know if it's serotonin or dopamine or what parts of the brain or the muscles, but I don't think anyone doubts that it works.

It does work. So we know from studies it does work and the same for, you know, cognitive therapy and mindfulness and meditation. We have good evidence from clinical trials that they work. We don't, we know even less about the bio, they're working by definition through [00:26:00] biology, you know, doing meditation for, we know we've studied monks and even normal people when they go through meditation and mindfulness training, how their brain changes.

And we're starting to learn more and more about that and how that changes even your blood pressure and certainly changes your anxiety and depression, but we don't know. don't really know what neurotransmitters are changed and what circuits are changed in the brain. But so I think that the holding the medications to a different standard than other interventions for mechanisms isn't fair.

We should keep all the things in our arsenal and use whatever works for whatever person to get them better. I think the understanding of biology is really interesting. It's interesting to me as a scientist, and hopefully will get us to a point where we can develop new interventions that work better and new treatments.

But I don't think it should influence how we think about our own treatments today.

Quinn: I think that's incredibly reasonable. Again, it can all [00:27:00] be applicable. It can you know, you can consider the whole thing and go further to other like lifestyle things like, you know, in our previous conversation, we talked about your work on residents and doctors and things like that.

But again, understanding that we're doing a lot of this live because the more we pick apart the brain and the gut, the more we're just like, oh, okay, great. No idea where this goes. Let's find out. But knowing that, again, you know, I have, I definitely have people in my life who are dealing with a lot of longstanding issues that may or may not be exacerbated by long COVID.

You know, it's easy to say, like, have you figured out what it is? It's like, it's probably closer to what are they? And all the different pieces and levers, you know, it's like a Rube Goldberg machine at this point. At the same time, understanding again, they're like, we just only know so much. And so, you know, when I talk about this with them, we try to separate in parallel where we can.

Separate relieving symptoms, right? And [00:28:00] trying to understand what a cause is, if we can even find that, if it's something that can even be controlled in some way. Right? Like it's pretty easy to back up and go like, hey bud, you're just, you're not getting any sleep. You know, not that's necessarily the root cause of something, but it's pretty easy to go like, oh, that's a symptom and a call a potential cause type of thing, but for a lot of people it will not be.

Those would be two different things. So we do try to separate those out going like, look, at least if we can find things that relieve your symptoms, but that do not have too adverse side effects, we're not going to make the cause worse or whatever it is. Great. You know, this show, my work, we try very hard to not barter in snake oil of any sort.

There's so much pop psychology stuff that is a nightmare and so much correlation where causation isn't even considered, it's a nightmare. But there is something to like you're saying going, oh, we got the monks in the MRI machine and going like, look, meditation is not for everybody. It can be a real pain in the ass, or you can fall asleep, all [00:29:00] of these things.

But if it helps, it is not going to hurt you. It's like acupuncture, right? It's like you've been doing it for 3000 years. Like it's not, you're going to be fine, but you also might be a little better than fine. And it seems like with the prevalence of most SSRIs. I mean, again, like how many billions of people have taken them in some form and for how long that we know again, yes, there are side effects and they're different for everybody, which is kind of why almost like the birth control pill, like you got to find what works for you.

But they could help. And along the way, folks like you are going to keep trying to figure out exactly how they work and why they work for some people and not.

Srijan Sen: Right. That's exactly right. And I think it's important to know that they weren't really designed. It wasn't like someone thought that I think serotonin is important.

We're going to develop this drug to target that and then see if it works in depression. It was more that there were a few different lines, but like, you [00:30:00] know, anti-tuberculosis, people were giving tuberculosis treatments and notice people taking these meds seemed a little happier and then trying to reverse engineer what it is, what is about this tuberculosis treatment that's helping mood and then find other drugs that kind of seem similar.

It was mostly from finding medications that worked and then and giving them rather than understanding anything about the mechanism that led to it and that's true for a lot of the other depression treatments as well, you know there's a lot of interest these days about ketamine and psilocybin and these are older psychedelics that we also don't really know the mechanisms of.

There's lots of interesting work going on in animal studies and trying to understand what receptors they work on, what parts of the brain, but they're incredibly broad drugs that affect lots and lots of different things. And we don't know why they help, why they affect our [00:31:00] thinking and our mental health.

But it's more that they probably do and trying to understand how they do is interesting, but more I tend to, in terms of patient decisions, try to go to the clinical trials and understand whether they work and then get to, you know, who they might work for much more than trying to understand the mechanisms in making individual decisions on treatment.

Quinn: Well, it really is like two parallel paths, right? And again, people in my life, it's easy to go to a first grade teacher and say like, oh, how are you not keeping up with the latest on the mental faculties of how first graders work? And they're like, well, I'm paid $20, 000 a year and I spend my day with five year olds.

I don't have the time for that. And it could, same could be said for like the very few primary physicians we have left. Right. Which is like, sure. It'd be great if like your doctor was a nerd who went home and studied this stuff, but their job is to help people feel better each and every day.

They don't have the time or the bandwidth. to do that, [00:32:00] or honestly, in the US like the incentives to do that, right? It's surgery or not basically. At the same time I guess it's important to have that, I just keep coming back to this idea of like, we're doing it live, but how do we share that in a, again, a candid way that still makes people feel solid about what they're doing.

And I always come back to and there's the big example we'll talk about in a second but I always come back to like, what, like you were saying in 25 years, we're going to look back and be like, holy shit, can you believe someone said that, you know, it's crazy. And chemotherapy is always the one I think of, which is like, someday we're going to look back and be like, Jesus, that was our first option for how long, for how many people, like the world's bluntest instrument, is often worse than the cancer itself, but it's also what we've got right now, you know, immunotherapy is really cool. Also really doesn't work for a lot of people. We're not 100 percent sure why. The big one on the block and I think this probably applies to mental health too, because it seemingly applies to everything, is these [00:33:00] weight loss drugs, Ozempic, et cetera, et cetera.

Every week, we're finding out more and more what they do, and we really don't know why. And there's some positives and negatives there, maybe? We're not sure, but that doesn't mean it hasn't improved so many people's lives in a huge way.

Srijan Sen: It's amazing, and there's so many interesting directions and consequences of Ozempic and that class of drugs.

But the profound effect it has on obesity and diabetes is incredible. And certainly there seems like there's some side effects and muscle loss and overall that, that, that seems really positive. And there seems to be interesting intersections with behavior and mental health too and particularly around addiction and maybe on mood and in different ways.

So, you know, seeing how that plays out, it's going to be fascinating. And also, you know, I think how it affects, I think in a sense, we thought of obesity and how much we eat as somewhat of a [00:34:00] moral or ethical question and seeing how much it changes and I think there's some aspects of that in mental health as well and how much a new type of drug completely transforms something that seemed somewhat mystical into like a purely like practical thing is interesting. And I hope that we have incredibly effective drugs that 90 percent of people with depression respond to in five years or 10 years. And a lot of these philosophical questions are no longer philosophical questions.

Quinn: And I love the philosophical questions.

Like I'm again, liberal arts major who barely graduated, long story, but I am like, when I look at these tech companies, I'm pulling out AI, they're incredible, going to change the world. But I've always believed that these companies should have a like Chief Should We Really Fucking Do This Officer?

Like in their C suite, someone who is liberal arts, who's like, who gets to ask the questions? Why do they get to ask the questions? Who's this going to affect adversely or not? Who's [00:35:00] incentivized to do this? Who's going to benefit? Do we really have to make money this way? Like, that's all really helpful.

And when you have like, I think it's Ozempic who is it out of the Netherlands, I can't remember which country it's out of, where it's like it has changed their GDP for the past, like 18 months, like completely, because it's so crazy and all that's great. We should keep asking those questions. You know, I saw an article this week, I can't remember, was talking about how pregnant women have started taking it because there's a lot of weight gain and that can feel horrible.

Again, this can be an entirely different conversation, but you know, some scientists and doctors are like, well, hold on though, we don't know what that's going to do to the placenta and the fetus and delivery and afterwards and brain health and all that, my first comment would be like, we don't study pregnant women as it is, which is a nightmare in itself.

So, we can start there, but you have to empathize with why they might want to try it, certainly, when you hear all this about it, but again, it doesn't mean it's not helping people along the way. And we, it [00:36:00] doesn't mean we can't keep asking questions along the way.

Srijan Sen: Yes, yeah, but keeping those on, yeah, keeping both those tracks going, but not interacting in unhealthy ways, I think is important.

Quinn: Unless there are, I mean, look, red flags come up and you pull something off the market. Like it wouldn't be the first time we've done that sort of thing. It's just, it requires intentionality, I think. Let's talk about the non pharmacological things, because there are things people can do.

Obviously in the last conversation, we talked a lot about sleep. And everyone has heard so much shit about sleep hygiene. It's not that complicated. You can use a watch to track it if you want, but you get the idea. It's kind of like tracking your food. If you know, if you're able to, after a week, you're like, no, I got it.

I got it. I know what I'm doing here. Let's talk about exercise. Tell me about, for folks who are able to exercise, which obviously is a pretty broad term. How do we know that this helps? What does it help with? And are there sort of measurable 10, 000 steps type stuff where people can go like, this is the [00:37:00] sort of thing maybe I could adopt to complement or be in place of or whatever my mental health regimen.

Srijan Sen: Yeah, I think starting with tying it all together with the medications, there are a lot of, there's SSRIs, here are, you know, many different types of SSRIs. There's other ones that are close to that, like SNRIs that are slightly different and other classes of medications. There are therapies that we, you know, have mostly heard of like cognitive therapy and mindfulness and interpersonal therapy and they all kind of work probably something like 40 percent, 50 percent of people respond to any of them, but it's a different one that different people respond to and right now people tend to go through lots of trial and error.

Some people are lucky and the first thing they try works. Some people have to go through four medications and three therapies before finding what works or what combination works. And some [00:38:00] people, none of the conventional ones we have work. And we don't really have a good way of figuring out what's going to work for what person.

Quinn: What your cocktail is going to be. Yeah.

Srijan Sen: Yeah. Yeah. And so we're doing work and other groups are doing work to try to see if anything from people's histories or how they're thinking now or some of their wearable data or genetics or other things can help us identify, you know, you're really gonna, you're likely to respond to Prozac or you're likely to really do well with with mindfulness.

Quinn: For psilocybin.

Srijan Sen: Right. Exactly. Or you, these things are probably not going to work from you and you're probably going to need, you know, ketamine or electric convulsive therapy and not going through five years of trial and error and just skipping to that. We're not there yet, but we're hoping to get there.

And the same kind of thing I think applies to things we don't consider typically as part of, the typical regimen of things that a doctor would prescribe, but are [00:39:00] effective treatments and interventions for depression, anxiety. So exercise is amongst those and it really helps some people a lot and some people it doesn't help that much. It rarely harms, but there is, you know, genetics and other things that we and others have done work in predicting if you're going to respond well to exercise. And if it's important to you, there's no magic number, like. You know, 10, 000 steps.

It's probably, it's reasonable. And, but, you know, getting 3000 steps is better than getting 2000 steps. And doing anything at all is probably the most important thing. And then there's marginal benefits to doing more. So I think exercise is really good in a lot of things for physical health, cardiovascular health, clearly for mental health, clearly for staying well.

And even if you are depressed and sick to get better. I think the there's studies comparing different kinds. There's a meta-analysis came out [00:40:00] last week that found like dance was the most effective type of exercise. I'm not sure if that's true. I think it's probably more people who'd be willing to do dance as an intervention or different than people who wouldn't.

Quinn: But great. You know, it's like, I keep, I'm wrestling while you're thinking of like, do I use the term like broad strokes telling people like you don't need to become a triathlete, you know, like you said, 2000 steps is better than 1000 steps, or is it? You don't want to dumb it down to like lowest common denominator, but it's the idea that like, something is better than nothing, and a little more something is better than something.

It's the same thing as, and again I know there's been studies on this, and that, and it's easy to feel like it's sort of softish science, but like, exposure to nature, which seems to be really great. If you don't, if you have any access to it and you're not doing it a little bit, I don't know, it seems to help.

Srijan Sen: A little bit. Yeah, exactly. And I think there's getting to be more real science behind all of this. And I think it's so I think the important points[00:41:00] are that just a little bit is clearly better than nothing.

Quinn: And is multi solving. Like you said, I mean, cardiovascular, et cetera, et cetera.

Srijan Sen: Yes, exactly. If walking is easier than riding a bike, then walk, if whatever it is, even if it's standing up, you know, during meetings or, you know, whatever it is that is easiest for you to do you should do it. It's not as clear that, you know, running a marathon is better than running a half marathon.

The benefits at that level are pretty small but doing something instead of nothing and whatever it is, is great. I think if there's a way to do it in a way that also is social. That's even better. So physical activity that is part of a group and creates more social interaction seems like it's better than ones that aren't.

But really whatever you can do is great. And then as I was sort of alluding to with the medications, really figuring out what [00:42:00] works, for some people, exercise is a game changer and really is the key to their staying healthy. For other people it's other things.

It's more in, you know, in sleep or the quality their personal interactions and for other people, maybe more diet. I think that being experimenting with yourself and understanding what sort of is the, maybe the key is too strong, but the elements that most affect you and as we talked about before, trying to keep track of your mood.

You don’t need the one to 10 system, but some system and being able to figure out like, oh, really I've been better about, I've been, you know, three days a week for the last month I've been going for a long walk and my mood is better on those days or not. And figuring that out is really valuable.

Quinn: Yeah I appreciate that. It does seem like, and again it's asking in some ways for you to just use your phone. You could use a journal, but checking it there, at least, you know, Apple [00:43:00] has built in these things now where you can very easily check in. You can even journal a little more. I've always used, it's different from that.

I've used Day One journal for 15 years and it's fun. It shows you like on this day eight years ago, this, and often, I'm not kidding, I'll send you a screenshot. Like most of my entries are just me saying I'm tired. So that's great. Good to know nothing has changed, but it is interesting. But this checking in, just the act of it, but again, enabling like a more valid retrospective, I think is probably a little helpful there for you.

And I imagine when you do get up the nerve to go talk to a psychologist or a psychiatrist or a social worker, whatever it might be, someone who you might want to have talk therapy with, or someone who might be able to prescribe a medication or both, like having that data for yourself and for them. I imagine can further your own interests in some way.

Srijan Sen: Yes. Yeah, exactly. Exactly. Yeah. You know, I want to check out that what did, Day One [00:44:00] you said?

Quinn: Day One. It's a journaling app. I don't know if it's Mac or Apple only. It's been around for 12 years, something like that.

At least that's how long I've had it. It's great. And, but now Apple has got their own journaling thing built in. It's not as powerful. The point is like, there are tools and they're there and you can start to use them and they're not going to solve everything, but just knowing yourself a little better without being one of those crazy people like myself who can check too much data.

Srijan Sen: Yeah no. Yeah, but it's good to do. Yeah. I haven't, I've been trying to use the Apple one, but it's at least on my iPhone. It's only connected with Peloton. So like the only thing it asks about is like, how did your afternoon strength session make you feel? And I'm like, I don't know if that's like the most important thing in my life, but.

Quinn: I guess we'll do some tech support on that. Mine is just like, what are you annoyed about today? I'm like, how much time do you have Apple watch? I think this is all really helpful. Again. I hesitate to say like, hey, what are like three basic questions someone should ask when they go into their [00:45:00] first possible talk therapy appointment, or their second with someone different because the first one didn't feel right, or when they're going in to think about medication for the first time. Mine was a little easier because I was just like, oh, let's not have a heart attack. Tell me what the things are and I'll just do them.

But other people are going to be a little more nervous. Like if you have any thoughts on that, like how to best sort of not steal themselves, but be prepared to go in. This is a great moment to share them or not. It's up to you.

Srijan Sen: Yeah, I don't think there's a exact right question or set of questions, but I think being as open as possible about your own anxieties or questions about different approaches, because like I mentioned, there are a lot of different choices.

I think often the main first one is medications versus therapy. And often times we have sort of underlying [00:46:00] beliefs or thoughts about which one is better for us. And I think being open with the therapist or psychiatrist and ourselves about that is important. And this is an area where there is a psychological and, you know, a placebo effect gets a negative term but it has a role in this, in depression.

And so if we, if five of our friends got much better with Zoloft, we're probably more likely to respond to Zoloft. Certainly if our, if people in our family, got better with Zoloft. There's probably a genetic component and that affects us. But if you have a strong feeling towards mindfulness, then that's probably the right choice for you.

And you should try it. And so being, don't, not being sort of dictatorial with the therapist or doctor but being open about what your thoughts are and what, you know, if you are leaning one way or another, don't doubt that and go with it and be open about [00:47:00] that conversation.

And if you feel like you're really hesitant about medications for some reason, then, you know, that's reasonable and maybe starting with something else as long as it's not, you know, very severe makes sense. But like you mentioned these are, as medications go, SSRIs and other sort of first line depression drugs are, at this point, you know, hundreds of millions of people have tried, have taken them and we know that they do have side effects and they change, but they're relatively mild as medications go.

Quinn: I think that's all totally helpful and fair. And you know, as a reminder to, and I this is slightly hypocritical because considering I've made it my job, but like, you don't need to understand all the science to go to someone to ask for help. There are a lot of really well meaning people like yourself who are trying to pursue these causes and understand them better.

And in the meantime, you can try to get help from the things we know that help a lot of people, not everybody, [00:48:00] maybe not even most people, maybe someone in your family, maybe not. But the good thing is there are a few things that seem to help a lot of folks and finding your version of that doesn't require you to get a degree from Reddit on the neuroscience of serotonin.

If you're interested in that, amazing, but don't let that dictate whether you go and try to get as much help as you need.

Srijan Sen: Understanding serotonin does not, is not going to help your treatment or your psychiatrist understanding serotonin is not going to help your treatment at the phase, I think at any time, but certainly at the phase of science we're at, hopefully it can help them, you know, be part of developing a new treatment in the future but we're not there yet.

And even broadly of the outside of serotonin or biology, trying to get to the root causes of your depression or anxiety, I think we're at a stage where we [00:49:00] can do that at a sort of proximal level, like in current things in your life, like not a lot of it is around sleep and sleeping well, or you know, stressors that, you know, someone close to you just died, or there's a really difficult relationship, or whatever, you're, you know, you have a new job and you're commuting six hours a day, stuff that's going on right now, understanding how that's affecting you.

Quinn: There's some low hanging fruit usually.

Srijan Sen: Yeah. And intervening on those and talking for that's very helpful. The deep thought at how sort of things 30 years ago are affecting you. Sometimes there's breakthroughs, but most of the time it's really hard to tie together. I mean, I'm summarizing, you know, hundreds of years of Freudian psychiatry in two sentences, but it's hard for those to lead to practical solutions in a way that's or, you know, certainly to medication choices or treatment choices.

And so, but people still get better, but [00:50:00] it's not, usually it's not by finding the underlying cause and fixing it. It's finding things that help people get better and getting more exercise and sleeping better and finding the right treatment is part of that, even if it doesn't feel like it's, you know, existentially solving the underlying problem.

Quinn: And exploring those problems. And if talk therapy, whatever version, CBT, works for you, that's amazing. I mean, finding someone I, again, I've been through a lot of folks. Not because I'm a monster. I mean, I am in some ways, but knowing what I'm, it's pretty clear to me, like what I don't want.

So finding what I want is a little harder, but once I do, it is so helpful to have someone who's like, no, let's talk about the hard shit, you know, because there's so many strings attached to everyone else in your life about doing that. That is the whole point of having someone like that.

Srijan Sen:Right. And it sounds like you resonate really well with the psychiatrist who is pretty blunt.

Quinn: He’s like, absolutely not. We're not doing that. Nice try. And that's great. That doesn't work for other people. Not for everybody. Yes. [00:51:00] Yeah. But my cocktail is also, and has always been exercise and it is newly medication and it is I am crazy about sleep stuff.

Srijan Sen: I wish we were in a place where we knew like, it's those exact things for everyone, but figuring that out for yourself and that self discovery is so critical.

Quinn: It's funny for as much as we really don't understand the brain, much less if it's like tied to the gut, like, God forbid, we're in even more trouble or it might be amazing. I don't know.

Srijan Sen: I like to think of it optimistically as this.

Quinn: Yeah. Yeah. Let's do that. So much fun. We'll do that. Great. So much to learn. This is so great. It's hard though, to be optimistic if, and this is more, probably applicable to more systemic things, which this could be, if you have been down a lot of roads and tried a different cocktails and tried a bunch of different versions and combinations of things to not want to go like there's gotta be some cause that's missing that I have not tried, because I have tried Zoloft and Prozac and Klonopin on the side, and I've done exercise, and I've done three types of exercise, and dance, and social and [00:52:00] non social, I've tried support groups, and all these different things.

I sleep, I've got the blackout curtains, and feel like there has to be something I haven't unlocked. It's hard to not want to be someone who learns how to read research papers and go like, oh, this changed. And go to your psychologist. He's like, I don't know. I've been at work. I haven't seen that paper that was published yesterday.

I do empathize with that. I do get that, you know, because you do have to be sort of your first line of defense a little bit, right?

Srijan Sen: Right. Yeah, no I completely understand that. And there are a lot of people like that. And it is important and that it's that is our fault as a field as a, as psychiatry and mental health and psychology.

It's, we don't have solutions where we haven't figured out those solutions for those people. And we don't have, you know, the equivalent of Ozempic for anxiety yet. And so, but it's not their fault for not responding to those [00:53:00] treatments and it's perfectly understandable to always, to be searching and to try to find the newest thing that could help that's perfectly understandable.

And hopefully we get something like that soon.

Quinn: And there are middle grounds, by the way, like America's clinical trial system is a bit of a nightmare, but you know, there are places you can look to try to get engaged with these things that aren't necessarily pharmacological. I mean, these studies about exercise and stuff don't come out of nowhere.

I mean, sometimes they're observational or retrospective or whatever, but you know, there are things you can do and questions you can ask and ways you can try to help yourself along the way. And I, again, I keep kind of coming back to a lot of these folks with long COVID who, you know, are running into conditions or of a potpourri of new conditions that they didn't know they were susceptible to having genetically, or are brand new, or suddenly have a new cardio problem because of COVID.

It's really hard to look around and go like, okay, who's the best person to talk about this? And you go [00:54:00] like, well everybody, the best people have only been dealing with this for 18 months, you know, and there's very few of them because we had plenty of health issues before that.

They still have their day jobs on top of this long COVID stuff. So you have to have some empathy there too, going like, it's a pretty narrow, small field, not that they're not trying, but we're still figuring out again, almost like cancer, and this is another terrible analogy. You're welcome. Which is like long COVID is not one thing, just like blood cancer and a tumor are very different.

It turns out it could be any combination of like 13 things. Finding someone, the one person who's going to help you there is a little tough.

Srijan Sen: Right. Right. And yeah, and they're still figuring it out, like you said. And it's, I think there's a lot of overlap between long COVID and our mental health and the same thing is true in there's not one depression or anxiety.

It's really different. And pain is another thing in this sort of class.

Quinn: Yeah, pain's fascinating. [00:55:00]

Srijan Sen: Yeah, it's really fascinating in lots of different ways. And we, but we don't, what you feel after you, you know, whatever, like sprain an ankle is really different than cancer pain or and the intervention should be really different, but we call it the same thing and we don't, and this is more true for depression than pain, but we don't understand the underlying processes, either psychological, social, or biological, to differentiate in the right way to sort of carve out the different types of depression, and so we kind of still treat it the same way and I hope we're much better at that in the future.

And again, can be more precise that like with the, if you have these symptoms of depression and this history and this genetic profile then Prozac is the right thing for you. But you have this other constellation of symptoms and history than cognitive therapy, but we're not there yet.

And post COVID symptoms and is even farther in its infancy [00:56:00] and farther away from that. So it's a challenge with this class of symptoms and disorders.

Quinn: I come back to, and I don't remember who the gentleman is and I'll find it. But a couple of years ago, I remember reading, I don't know, I think it was an MIT tech review or something like that.

It was an MIT researcher who was like among the best in like sort of the brain's neural pathways. And again, I don't remember who it was and I don't remember the context or the exact quote, but he was generally like, look, no one knows this better than I do, and we have no idea how a thought works and you're just like, shit.

Okay. Like, you know, you've got to really be pretty humble about that. Right. Which is just like, Oh, it happens. We don't know why. Right. Maybe whales too. Oh.

Srijan Sen:Yeah. And I feel, I mean, there are people who know it better than me, but not that many. And I have no idea.

Quinn: Like, so it's crazy and that can be wonderful, but I think if you're suffering, it can be just like but fix me.

You know? So knowing that there are options, knowing that yes, we're still sorting out the [00:57:00] serotonin theory and all this, and probably will for a very long time. That some things work for a lot of people and some things work for others and that there are things that are available to you.

Srijan Sen: I think another point that might be important is that we change a lot in our lives and as we, you know, develop and get older and also as life circumstances change.

And so what works for you know, what didn't work for you at 20 might work for you at 40 and 50 and vice versa. So, which makes it even more infuriating and complicated, but also there's hope and there's lots of things to try and try in a different way or that we're, you know, I've seen lots of times where particular therapies that didn't work or didn't take hold, maybe was one therapist or at one time in people's lives do work later on again.

Quinn: Well, it all sounds easy.

Srijan Sen: Yes. Yeah. It's unlikely that I'm going to be out of a job, so.

Quinn: Yeah. Right. I mean, [00:58:00] it's funny. I have that conversation with a lot of folks. I'm gonna let you go in a sec here, but you know, when I tell them that not all, because they won't be, because the problem is inherently not this, but a lot of charities and non profits, the best ones should be trying to put themselves out of business, right? It would be really great if we just figured out how to deal with pediatric cancer, right? Which is obviously 40 different things etc. Homelessness, all these things. But there's a lot of things that's very clear that, like, we're not going to be done with anytime soon.

I had this wonderful conversation with Cat Bohannon, who wrote a book that you would love called Eve. And it's about, I'm going to get the subtitle wrong, but how the female body drove 200 million years of evolution or whatever, essentially, it's fantastic. Also, she read the audio book and she's great.

And it's also funny. It's amazing, but she has this really great point about she's, you know, she's like, humans are really bad at pregnancy and delivery, like even relative to our closest [00:59:00] relatives, she's like, it's a nightmare. Like, you know, gynecology, thank God we invented that and figured it out.

Like we have to, you can be in the fanciest hospital and be in the most shape and have all the money in the world. And it's still like touch and go at times. She's like, that is ridiculous. Like it's not that way for like any other animal. And again, it's like, that is not something that's going away.

There's no way to like work our way around that, you know, and the brain and the gut and all that seem to be, much less how they're entangled seem to be other parts. And I mean, same thing, postpartum depression, right? I mean, holy cow. No, thank you.

Srijan Sen: Right, right. And how evolution plays into our mental health is really fascinating and interesting, I think can sometimes be helpful to think about.

So, you know, could be worth talking about in a future conversation.

Quinn: Yeah. Well, listen, I've kept you long enough. Have, I've asked you all the other questions. Have you read anything recently that you would like to share with folks about work, not about work, someone else's work, fiction, graphic novel?

Srijan Sen: Not a specific thing I read, but just [01:00:00] related to the, you mentioned charities and other things and just something that's been coming up in a whole bunch of different research studies more and more is volunteer work and how much, how effective that is for our own, I mean, it helps other people, but helps our mental health in ways I've seen it in my, in the population, I studied physicians, there was even a study recently of like workplace mental health interventions and almost nothing worked except volunteer work and a bunch of other sort of meta analyses showing pretty profound effects for some extent charitable giving, but even more volunteering and spending time on that. On depression and mental health. So, you know, I think not everyone can do it and not everyone has time but the more you can, it's again, we don't know the exact mechanisms, but it's hard to feel bad about yourself if you're volunteering and, you know, I think I've come to realize [01:01:00] more and more in how much it helps the person volunteering and is a good thing to do for people who are, who have the capacity to do it.

So, I mean, you know, I'm again, I think we need to learn more, and learn more who it helps, but I think that's a, that's another thing in the arsenal that we should use, I think, much more than we do, and hopefully that helps the world as well.

Quinn: Yeah, it's clearly not like, that narcissistic, right? I mean, there's an element of like, great.

You're running a marathon, buddy. Like, congratulations. I'm glad it makes you feel better. But like, what does that do for people? Not a whole lot versus some form of volunteering. Like Lord knows we need it these days, you know, whether it's anything, tutoring, handing out food, whatever it might be is amazing.

Srijan Sen: And I think that helps build community too, which is really important for, I think we know inherently it's good for the world and good for the community. But the fact that the extent to which it helps us being part of that is, I think, underappreciated. So that's, you know, tangentially [01:02:00] the one thing that came to mind to add.

Quinn: Great. I love it. We'll find some resources to share on that. Srijan, thank you so much for your time. Again, hopefully you don't regret it this time. I'm going to keep going until you feel like it's enough. That's all I got. Obviously, where can people follow your work? Just so we can put it out there.

Srijan Sen: Sure. I have my group's website and I'm on X or Twitter or whatever we're calling it these days, the University of Michigan Eisenberg Family Depression Center, which I helped direct also on Twitter and our website has a lot on the latest news and research and things people can do to stay up to date and take care of themselves.

So, happy to share any of those resources if it's of interest.

Quinn: Awesome. All right. This has been fantastic. Thank you so much.