Biomarkers for Depression (with Carla Nasca, PhD)

Dr. Carla Nasca is an Assistant Professor in the Department of Psychiatry and the Department of Neuroscience and Physiology at NYU Langone, where she studies epigenetic mechanisms of neuroplasticity to stress. Dr. Nasca's work led to the discovery of acetyl-L-carnitine (LAC), a metabolite found in the mitochondria, as a promising biological marker of depression.

Topics:

• acetyl-L-carnitine (LAC) and major depressive disorder
• How stress changes the brain on a structural/molecular level
• Risk factors for stress-induced disorders
• Machine learning

More information: https://www.cdr.rfmh.org/research/nasca-lab/

This discussion is for educational purposes and does not substitute for individual clinical judgment or patient care.

Senior Producer: Jon Earle

Transcript

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NOTE: Transcripts of our episodes are made available as soon as possible. They may contain errors.

[00:00:00] DR. THEA GALLAGHER: Welcome to NYU Langone Insights on Psychiatry, a clinician's guide to the latest psychiatric research. I'm Dr. Thea Gallagher. Each episode, I interview a leading psychiatric researcher about how their work translates into clinical practice.

This is the final episode of our first season and I'm so glad that it brings Dr. Carla Nasca to the podcast. Dr. Nasca is an assistant professor in the Departments of Psychiatry and Neuroscience Physiology here at NYU. Her research focuses on identifying biological targets in major depressive disorder. In our conversation, we talk about that, as well as the latest research on how stress affects the brain, and what machine learning could mean for precision psychiatry.

Thank you so much for being on our podcast, and we are just going to get right into it from the beginning. So, can you tell us a little bit about how you would describe your research focus?

[00:00:52] DR. CARLA NASCA: So happy to be here. My lab at NYU School of Medicine in the Department of Psychiatry and in the [00:01:00] Department of Neuroscience is working on epigenetic mechanisms of neuroplasticity to stress, with a new angle on the communication between mitochondria to cell nuclei. Prior studies show that histone acetylation is a key epigenetic mechanism that controls expression of key genes for brain plasticity. Our work, the work of our group, shows that mitochondrial metabolism can contribute a significant amount, a significant portion of substrates of acetyl groups necessary for a histone acetylation.

In the lab we work on animal models and we do basic and translational neuroscience research. First we identify this mechanism, this novel mitochondrial mechanism [00:02:00] of epigenetic function in rodent models of chronic stress. Chronic stress is a main risk factor for psychiatric illnesses. And subsequently, we translate these findings to humans and we provide initial evidence that this mechanism could serve as a therapeutic target for clinical phenotypes of depression.

In this audience, we know that one of the breakthroughs over the last decade was the discovery of the rapid antidepressant effects of ketamine. Ketamine is for its chemical structure, ketamine is an antagonist of NMDA receptors. NMDA receptors are important receptors of the glutamate system. They are ionotropic glutamate receptors that respond to high levels of glutamate to regulate glutamatergic signaling.

In my PhD work, initially in Italy and subsequently at Rockefeller University where I trained with Bruce McEwen, and now at NYU, shows that an alternative to the use of ketamine may be the use [00:03:00] of LAC, L-A-C. LAC or acetyl-L-carnitine, which is a key mitochondrial metabolite that serves as a donor of acetyl groups for histone acetylation.

At least in rodent models, the action of LAC is as fast as the action of ketamine in regulating stress-induced glutamate overflow and the corresponding structural changes that we observe in key neurons of the hippocampus. LAC acts as a regulator, as an epigenetic regulator of mGlu2 receptors. mGlu2 receptors are another class of important glutamate receptors that are [00:04:00] localized in the presynaptic terminal where they respond to low levels of glutamate to modulate rather than mediate glutamatergic signaling.

And this function is advantageous not only to achieve rapid antidepressant response but also to minimize the unwanted side effects that result from direct targeting of NMDA receptors.

And a a feature of all these rodent models of chronic stress that rapidly respond to supplementation with LAC to administration of LAC, was that these rodent models start with a deficiency of LAC. We observe decreased levels of this key mitochondrial metabolite [00:05:00] not only in plasma but also in brain areas such as the hippocampus and prefrontal cortex.

We are expanding this work in multiple collaborations with Huda Akil at the John Hopkins Uni—sorry, with Huda Akil at the University of Michigan, with and with, with Francis Lee at Weill Cornell here in New York. And we observe that the deficiency of LAC is a common denominator across multiple rodent models.

This work was the lead-in for our translational work to humans to understand whether this novel framework of mitochondrial, mitochondrial mechanism of epigenetic function has any relevance to humans. We want to answer first the simple question and understand whether patients suffering with major depressive disorder show a deficiency of LAC as do our rodent models of chronic stress.

So we believe that the whole is greater than the sum of its parts.

[00:05:42] DR. THEA GALLAGHER: Mm-hmm.

[00:05:42] DR. CARLA NASCA: I am a basic neuroscientist so I [00:06:00] started a collaboration with multiple clinical colleagues at Stanford Weill Cornell, including Francis Lee, and Mount Sinai, including James Murrough. They recruited a large number of patients suffering from major depressive disorders and age and sex match the controls. And we assess the levels of LAC in plasma. And as do our rodent models patients suffering with depression show a deficiency of LAC. They show about a 40 percent decrease in LAC levels as compared to controls. Another [00:07:00] important finding from that initial work was that the lowest levels of LAC were found we found the lowest levels of LAC in those subjects with a diagnosis of treatment-resistant depression as defined by-

[00:07:15] DR. THEA GALLAGHER: Hmm.

[00:07:16] DR. CARLA NASCA: ... at least two failed antidepressant trials. Furthermore there was an important role of childhood trauma that is a major form of stress in humans in that the lowest levels of LAC were associated with the higher reported rates of childhood trauma and specifically emotional neglect and emotional abuse. The lowest of levels of LAC were also associated with a higher severity of the disease.

So we believe that this deficiency in LAC may help to define severe clinical phenotypes of depression. These findings were replicated initially in two independent study cohorts and now there are multiple studies that show that a deficiency of LAC can be a therapeutic target for depression.

In subsequent work we tested our next scientific question. We wondered whether decreased levels of LAC could help to identify the subjects that respond or do not respond to antidepressant drugs.

In the initial study, we found that decreased levels of LAC together with metabolic dysfunction known as insulin resistance and again higher reported rates of emotional abuse or emotional neglect, [00:08:00] in childhood predict those subjects that respond or do not respond to antidepressant drugs. Specifically, those subjects with the lowest levels of LAC did not show any improvement in [00:09:00] depressive symptoms. Conversely, those subjects with major depressive disorder and the highest levels of LAC do show improvement in depressive symptoms.

We are also extending this framework of mitochondrial mechanism of epigenetic function in the context of Alzheimer’s disease. There is growing literature showing that depression can be a prodromal state or a risk factor for Alzheimer’s disease.

[00:09:31] DR. THEA GALLAGHER: Mm-hmm.

[00:09:31] DR. CARLA NASCA: So we wondered whether this mitochondrial dysfunction could play a role in the progression from depression to Alzheimer disease.

In initial work conducted mainly by Betty Bigio, a computational engineer in the lab, we started extending this work in the context of mild cognitive impairment in subjects with Alzheimer’s disease. And we find that in addition [00:10:00] to the decreased levels of LAC associated with cognitive dysfunction in Alzheimer’s disease, there is a very nice sex difference in carnitine levels.

Carnitine is the main derivative of LAC and the work is currently under review so we hope it will be published soon.

[00:10:20] DR. THEA GALLAGHER: Mm-hmm.

[00:10:21] DR. CARLA NASCA: And again I think that's important to say. So also in the context of not only in the context of clinical phenotypes of depression but also in the context of clinical phenotypes of cognitive dysfunction in Alzheimer disease our data show an important role of childhood trauma in that-

[00:10:43] DR. THEA GALLAGHER: Hmm.

[00:10:43] DR. CARLA NASCA: ...uh, the stronger deficiency, the stronger dysfunction in the mitochondrial metabolism seems to be consistently associated with childhood trauma.

[00:10:54] DR. THEA GALLAGHER: So this seems like a pretty major finding and novel in that, normally, [00:11:00] looking at SRIs, looking at serotonin, that LAC is a new finding. Um, and do you have an idea of maybe how it gets to this place of being diminished in certain individuals?

[00:11:14] DR. CARLA NASCA: Yes. So it's a great question. So in our initial rodent work we also compared the action of LAC to the action of standard antidepressant drugs like glutamate, I mean and fluoxetine and uh-

[00:11:31] DR. THEA GALLAGHER: Mm-hmm.

[00:11:31] DR. CARLA NASCA: ... in the same rodent models we find that the action of LAC is evident after three days of administration, whereas the action of standard antidepressant drugs required at least 14 days-

[00:11:44] DR. THEA GALLAGHER: Mm-hmm.

[00:11:46] DR. CARLA NASCA: ... of administration. Furthermore, we also find that when we stop administration of the drugs the antidepressant response of LAC is still evident for at least 14 days after drug [00:12:00] withdrawal whereas the antidepressant response to [inaudible] fluoxetine disappeared when we stopped administration of the drug.

This long-lasting action, this rapid and long-lasting action of LAC made us think about the possible epigenetic mechanisms. So we believe that LAC, which is an endogenous metabolite, so all our cells produce LAC.

[00:12:27] DR. THEA GALLAGHER: Mm-hmm.

[00:12:28] DR. CARLA NASCA: And LAC was initially best known for its role in fatty acid oxidation. This rapid and long-lasting action of LAC made us think that an epigenetic mechanism could be involved. And one key target of LAC is indeed the histone acetylation.

[00:12:47] DR. THEA GALLAGHER: And just explain a bit more. What were you able to—it sounds like you said you were able to do something to reinforce the, the, the LAC molecule? Or, or how were you able to do that as compared to [00:13:00] the clomipramine or fluoxetine?

[00:13:02] DR. CARLA NASCA: Yes. So LAC, in addition to being an endogenous endogenous molecule produced by our cells, LAC is is also a pharmaceutical drug. So we can administer LAC to our rodent models.

[00:13:16] DR. THEA GALLAGHER: Mm-hmm.

[00:13:17] DR. CARLA NASCA: It will be too early to take LAC in humans because there is need for additional studies, for additional research to understand what is the dose, what is the regimen of LAC that is needed to increase blood levels of LAC.

And also, we have ongoing work with the exosomes. I'm sure you heard about the exosomes and this is a new direction in our rodent model. So we find that the deficiency of LAC is not only present in plasma but also in important brains areas like the hippocampus and uh-

[00:13:51] DR. THEA GALLAGHER: Mm-hmm.

[00:13:51] DR. CARLA NASCA: ... prefrontal cortex. So far we could assess LAC levels only in plasma in [00:14:00] humans for obvious limitations because we cannot do a biopsy and assess LAC levels yet. And so we learned from the field of cancer about exosomes.

Exosomes are small nano vesicles that are excreted from all cells including cells of the brain. They cross the blood-brain barrier and express cell surface markers that are specific for the organ that releases them. So we can isolate the exosomes from plasma and subsequently reach for those exosomes that are released from the brain.

In this way, we can have a screenshot of what's going on in the brain of a subject at a given moment, overcoming the limitations of prior post mortem studies. And also peripheral molecular studies.

We are applying the technology of exosomes in the context of multiple clinical studies in collaboration with Dan Iosifescu, Charles Marmar, and Donald Goff and here at [00:15:00] NYU, as well as in collaboration with our clinical colleagues at Stanford. And exosomes are also the key topic of my new RO1 from the National Institute of Mental. It's an exciting new direction because exosomes will, we believe, we do believe that exosomes can open up the opportunity to yield temporal and spatial deep molecular phenotyping of molecular markers important for brain plasticity in vivo, overcoming the limitation of prior post mortem molecular studies.

We hope that this technology will help us to assess LAC levels in specific brain [00:16:00] areas relevant to depressive and cognitive disorders.

[00:16:01] DR. THEA GALLAGHER: And in the human studies that you've already done, you were able to identify that lower levels of LAC did correlate with MDD and it sounds like also impacted by childhood trauma and more severe levels of depression had lower levels of LAC. So you have done some human work. What will it take to get to the point where you can have a pharmaceutical work like you're doing in the rodents?

[00:16:31] DR. CARLA NASCA: Yes. So we need the more basic and translational studies and the integration between basic neuroscience and the translational neuroscience is key to identify new mechanisms and subsequently to characterize the role in, in rodent models, to identify new mechanisms in rodent models, and subsequently characterize the role in the context of clinical phenotypes of depression.

Not all [00:17:00] patients, as we know, respond to standard I mean patients respond in a different way to standard antidepressant drugs. And we need to take this heterogenicity as an opportunity to identify what are the mechanisms that enable a person to respond to specific treatment whereas another person does not respond to that treatment?

And with the integration of basic neuroscience knowledge and computational psychiatry, we can characterize specific clusters of subjects that are characterized, for example by deficits in mitochondrial mechanisms, in the mitochondrial mechanism of LAC and how these deficits map to specific clinical symptoms.

In our work in the clinical context of LAC, we show that the deficiency of LAC is highly [00:18:00] associated with specific symptoms such as suicide ideology and anhedonia. In particular we find that the lowest levels of LAC characterize those subjects with the highest suicide suicide ideology-

[00:18:13] DR. THEA GALLAGHER: Mm-hmm.

[00:18:13] DR. CARLA NASCA: ... and the highest anhedonia.

[00:18:17] DR. THEA GALLAGHER: I mean, this seems pretty, pretty powerful and pretty um, to help, maybe a group of people that has not benefited from traditional depression medication, SRIs and the like.

[00:18:30] DR. CARLA NASCA: Exactly. So because we also observe decreased levels of LAC in subjects with treatment-resistant depression meaning those subjects that failed to respond to at least two antidepressant trials we believe that LAC could be useful all, also as an augmentation strategy.

[00:18:53] DR. THEA GALLAGHER: Mm-hmm.

[00:18:53] DR. CARLA NASCA: But again, there is a need for additional research to advance important questions.

[00:18:58] DR. THEA GALLAGHER: Mm-hmm. Is that research [00:19:00] that's being done or in the works to be done? Is that research that you are excited about hopefully seeing come to life?

[00:19:06] DR. CARLA NASCA: Yes. So hopefully soon. So we have ongoing research first in animal models to develop a new molecule that we hope going to be even more important than LAC-

[00:19:19] DR. THEA GALLAGHER: Hmm.

[00:19:20] DR. CARLA NASCA: ... by specifically targeting this epigenetic mechanism of histone acetylation. And we are also working, translating our rodent, our basic neuroscience findings to subjects with clinical depression to identify those subjects that can benefit from augmentation of LAC. Not all subjects will benefit from taking LAC so we need to identify what is the cluster of subjects that is characterized by a deficiency of LAC, in a way that, by taking LAC, it will benefit.

[00:19:56] DR. THEA GALLAGHER: You were talking earlier about [00:20:00] childhood trauma as a factor that plays a role in stress and in depression. Um, do you have an understanding of how these all might impact LAC here?

[00:20:14] DR. CARLA NASCA: So there is prior work from Michael Meaney and many other colleagues showing that early life stressors starting from the nurturing environment, so from a maternal carer, can lead to long-lasting change in the epigenome and in DNA methylation.

We extended this work showing that our rodent models of chronic stress, including stress in adult life as well as stress in the nesting environment, so a maternal carer, can lead to change in mitochondrial metabolism of LAC with the corresponding change in histone acetylation and regulation [00:21:00] of key genes of the glutamatergic system.

Among these gene is the mGlu2 receptor which is a key inhibitor of spontaneous glutamate release in rodent models we find, after chronic stress, we find that there is a robust overflow of glutamate-

[00:21:22] DR. THEA GALLAGHER: Hmm.

[00:21:22] DR. CARLA NASCA: And this leads to structural change, to spine loss, retraction of dendrites in the hippocampus as well as in the medial amygdala, which is a brain area also important for sex differences. And by the administration of LAC we can regulate the epigenetic programming of glutamatergic function to ameliorate the facts of chronic stress or of early life stress on brain plasticity and behavior.

[00:21:56] DR. THEA GALLAGHER: And um, talking about—kind of switching gears to [00:22:00] machine learning, a big theme of this podcast and in this season has been talking about precision psychiatry, precision medicine. It sounds like this is something you feel strongly about as well per your paper that you authored last year. Can you tell us a little bit about your thoughts on machine learning and, and how—where you hope to see the work go?

[00:22:26] DR. CARLA NASCA: So this audience will know that there is a lot of heterogenicity, not only in the pathophysiology but also in treatment of depressive disorders. And I believe we need to take, to transform this issue of heterogenicity into an opportunity. Because beyond those differential responses to antidepressant drugs there can be different mechanisms that differentiate those subjects that respond or do not respond. And if we can identify the [00:23:00] molecular mechanism that allows a person to respond then that mechanism can serve as a therapeutic target for the person who is not responding.

[00:23:11] DR. THEA GALLAGHER: So understanding the various mechanisms, the biological—the biomarkers and potentially, it sounds like some of the life experience, that looking at all of these things together will give us a better picture of the individual. Where it seems like a lot of the models of empirically supported care, whether it's psychological or psychiatric, do not positively benefit everyone.

[00:23:40] DR. CARLA NASCA: Exactly. So we need a multidimensional approach to understand how multiple biological factors map against specific clinical symptoms. In our translational work, we showed that aberrant mitochondrial metabolism is also associated [00:24:00] with leukocyte telomere length that is a marker of cellular aging in addition to metabolic dysfunction in the form of insulin resistance as well as in the form of increased body mass index.

And these biological pathways are associated with high reported rates of childhood trauma with trauma that starts in early life. So we needed to use a computational approach to integrate these multiple molecular pathways not only with the clinical features but also with the information that the patients gave to the psychiatrists.

For example we use the CTQ, which is the Childhood Trauma Questionnaire to understand the—to listen, I mean to understand the rates of childhood trauma.

[00:24:59] DR. THEA GALLAGHER: And it sounds like [00:25:00] the more we can, we can do this work in a machine learning-informed way, we can have more accurate diagnoses, prognoses, monitoring, and, ultimately treatment in, in the clinical setting.

[00:25:15] DR. CARLA NASCA: Exactly.

[00:25:16] DR. THEA GALLAGHER: I-is there any, any part of your research that we haven't yet discussed or that you are really excited about or something that you see for the future that will have an impact on clinicians who are treating patients?

[00:25:28] DR. CARLA NASCA: I think yes. So the two topics that are exciting to me are these novel mitochondrial mechanism of epigenetic function and the utility of exosomes as a tool to translate these to identify and characterize the role of these mitochondrial mechanism in in a clinical, in subjects, in patients with depressive disorder because otherwise we'll not be able to [00:26:00] understand to have the screenshot of what's going on in the brain of a patient at a given moment.

So we believe that the exosomes can really be a strength and a powerful tool for clinical studies.

[00:26:16] DR. THEA GALLAGHER: And in the work that you're doing with Dr. Iosefescu, Dr. Marmar, Dr. Goff—what are you hoping to be able to—is the hope to build on what you were just talking about here and having a better understanding of these mechanisms and then allowing for more precision treatment?

[00:26:35] DR. CARLA NASCA: Yes. So it's really beautiful collaboration where we bring together our knowledge from different perspectives, so from Neuroscience to Psychiatry, to integrate and understand the role of a these novel mechanism of brain plasticity and in the context not only of treatment-resistant depression but also in the context of [00:27:00] other disorders like alcohol use disorders that are also characterized by aberrant glutamatergic function.

And with the use of exosomes we can identify those subjects with—the idea is to use exosomes to characterize the clinical responses in the context of these different diseases.

[00:27:32] DR. THEA GALLAGHER: And can you describe exosomes again, exactly how it works to, like you said in living samples, you're able to get a snapshot of the brain that informs mitochondrial function?

[00:27:44] DR. CARLA NASCA: Exactly. So we leverage properties, biological properties of exosomes. Exosomes have a small diameter. They are very small vesicles with a diameter of about 30 to 100 nanometers. They [00:28:00] cross the blood-brain barrier and are released in the circulation. So those exosomes that are produced by the brain are able to cross the blood-brain barrier and are released in the circulation in the blood.

Exosomes are vesicles with a membrane and on the surface of this membrane, they express this, they express specific markers that are released for the or- that are specific for the organ that released them. So that there are exosomes that express surface markers, like L1CAM is a protein [inaudible 00:28:38] expressed in the brain.

So we train from blood we isolate the plasma and subsequently we target those exosomes that express these marker, L1CAM as well as many other markers that are high expressing in the brain to isolate exosomes to immunoprecipitate that specific pool of [00:29:00] exosomes that is released from the brain.

Subsequently, we break the membrane of these vesicles and we can characterize the molecular cargo that they contain. In this way, we can, starting from plasma, we can have a screenshot of the molecular cargo, or the molecular fingerprint-

[00:29:21] DR. THEA GALLAGHER: Hmm.

[00:29:23] DR. CARLA NASCA: ... that is of the brain of a patient at a given moment.

[00:29:28] DR. THEA GALLAGHER: And so it sounds like it's a pretty non-invasive procedure then, if it's-

[00:29:32] DR. CARLA NASCA: Exactly. Yes.

[00:29:33] DR. THEA GALLAGHER: Yeah.

[00:29:33] DR. CARLA NASCA: Yes.

[00:29:33] DR. THEA GALLAGHER: Looking at plasma, right?

[00:29:34] DR. CARLA NASCA: Exactly.

[00:29:35] DR. THEA GALLAGHER: Mm-hmm. So it seems like you would be able to assess a large number of people in a fairly quick and non-, you know, non-invasive manner.

[00:29:46] DR. CARLA NASCA: Yes.

[00:29:47] DR. THEA GALLAGHER: Do you think this would ultimately be something that—is the hope that when you get a blood test or get your blood taken and looked at that this [00:30:00] could be something, like maybe just part of your regular blood workup? That this could be something that could be observed or looked at as maybe a risk factor or-

[00:30:11] DR. CARLA NASCA: All right. So in the long term, we hope that exosomes can also serve as a non-invasive diagnostic tool. And if we can characterize the molecular cargo of exosomes so that they differentiate a subject with depressive disorder from healthy controls-

[00:30:19] DR. THEA GALLAGHER: Mm-hmm.

[00:30:20] DR. CARLA NASCA: ... or a subject that responds or does not respond to specific treatment, yes. We hope that it can serve as a biological marker. But exosomes can also be engineered with specific molecular markers. So if we identified a specific molecular cargo exosomes subsequently with the help of basic neuroscience studies, we can [00:31:00] reengineer exosomes with cargo that is specific to what we found to be aberrant in a patient. So they can also serve as a new therapy in the long term.

[00:31:14] DR. THEA GALLAGHER: Mm-hmm. So diagnosis and then it might be able to assess people at an earlier state and get them the help that they need.

[00:31:23] DR. CARLA NASCA: Exactly.

[00:31:23] DR. THEA GALLAGHER: So for diagnosis and treatment, it sounds like it could be a really amazing breakthrough. And when we're talking about depression there's so many different factors that we sort of understand impact depression. Um, there's connections, say, with exercise and weight and, you know SRI medication and different types of talk therapy. Um, is it overwhelming when looking the different things that might impact depression? Or is it ultimately to understand more and then use machine learning to understand exactly what is [00:32:00] impacting the individual and impacting their depressive state?

[00:32:03] DR. CARLA NASCA: Yes. So it's very important, actually, to understand the lifestyle of a person. We have unpublished data in a beautiful collaboration with a colleague in Japan showing that regular exercise increases LAC levels.

[00:32:19] DR. THEA GALLAGHER: Hmm.

[00:32:19] DR. CARLA NASCA: We know this at least in rodents and yes, so there are also many studies in humans showing that regular exercise is an important antidepressant.

[00:32:33] DR. THEA GALLAGHER: And do you have a sense of when we might see this research with human subjects? Is there a goal—10 years, 20 years?

[00:32:52] DR. CARLA NASCA: It's hard to say. But I believe that I mean so far we are contributing to understanding what [00:33:00] are the biological mechanisms underlying the pathophysiology and treatment of depression. As I mentioned, we are also working on developing a new molecule but it takes several years of research.

[00:33:16] DR. THEA GALLAGHER: Mm-hmm. And since you are collaborating with some psychiatrists on that, on the other study, the exosome study you were discussing, is there any advice you would give for psychiatrists who are practicing who work with patients on a day-to-day basis? Um, hopefully they're listening to this and are hopeful that maybe future research can help some treatment resistant patients. But anything you would like clinicians to know or understand about your research that could inform their work?

[00:33:45] DR. CARLA NASCA: I think what this department is doing is just beautiful. And the integration and not the compartmentalization but the integration between basic molecular neuroscience and translational neuroscience is well reflected in these departments and is a key for [00:34:00] precision medicine.

[00:34:07] DR. THEA GALLAGHER: Yeah. And it seems like—again with the theme of this podcast, really, ultimately it's been a nice synergy that most everyone is saying we need to use these machine learning models to hopefully further the science um, and create more precision Psychiatry methods that will help people more accurately, more quickly, and more effectively.

[00:34:33] DR. CARLA NASCA: Yeah. Right.

[00:34:35] DR. THEA GALLAGHER: Wonderful. Well, thank you so much for being on the podcast.

[00:34:39] DR. CARLA NASCA: Thanks. My pleasure.

[00:34:41] DR. THEA GALLAGHER: Thanks so much again for that conversation, Dr. Nasca. If you enjoyed this episode, be sure to rate and subscribe to NYU Langone Insights on Psychiatry on your podcast app. As I mentioned at the top, this is the last episode of our first season. Thanks so much to everybody who's appeared on the show. And thank you for listening. [00:35:00] Stay tuned for more episodes down the line.

Until then, for the Department of Psychiatry at NYU, I'm Dr. Thea Gallagher. Take care.