WEBVTT 00:00.000 --> 00:04.000 position:17.5%,start line:79.33% size:62.5% Welcome to Healthy Minds, I'm Dr. Jeff Borenstein. 00:04.000 --> 00:07.000 position:22.5%,start line:79.33% size:55% Everyone is touched by psychiatric conditions, 00:07.000 --> 00:09.000 position:27.5%,start line:79.33% size:42.5% either themselves or a loved one. 00:09.000 --> 00:11.000 position:17.5%,start line:84.66% size:62.5% Do not suffer in silence. 00:11.000 --> 00:13.000 position:17.5%,start line:84.66% size:62.5% With help, there is hope. 00:15.000 --> 00:20.000 position:22.5%,start line:84.66% size:55% Today on Health Minds: 00:20.000 --> 00:22.000 position:32.5%,start line:79.33% size:35% (Dr. Lisa Pan) We had tried literally 00:22.000 --> 00:24.000 position:15%,start line:84.66% size:67.5% every medication available. 00:24.000 --> 00:25.000 position:30%,start line:79.33% size:40% We had even done experimental medications and 00:25.000 --> 00:27.000 position:27.5%,start line:84.66% size:42.5% nothing happened. 00:27.000 --> 00:30.000 position:10%,start line:10% size:80% And in fact, at the time that we made this discovery, 00:30.000 --> 00:32.000 position:35%,start line:10% size:30% he was in an inpatient psychiatric facility, 00:32.000 --> 00:36.000 position:25%,start line:10% size:47.5% horribly depressed, on 17 medications 00:36.000 --> 00:37.000 position:25%,start line:10% size:47.5% just to try to keep him safe. 00:37.000 --> 00:40.000 position:20%,start line:10% size:57.5% And he was not having a response nor was he really 00:40.000 --> 00:42.000 position:10%,start line:10% size:80% having side effects so I had not ever seen anything like that. 00:42.000 --> 00:45.000 position:17.5%,start line:10% size:62.5% And so we repurposed this molecule and gave it to him 00:45.000 --> 00:48.000 position:32.5%,start line:79.33% size:35% and we started to see improvement. 00:48.000 --> 00:50.000 position:30%,start line:79.33% size:37.5% And we saw some fascinating changes. 00:50.000 --> 00:55.000 position:12.5%,start line:79.33% size:72.5% He is now four years healthy, I'm sorry, five years healthy 00:55.000 --> 00:58.000 position:20%,start line:79.33% size:57.5% and with no psychiatric medication just with this 00:58.000 --> 00:59.000 position:22.5%,start line:84.66% size:52.5% replacement molecule. 00:59.000 --> 01:01.000 position:30%,start line:79.33% size:40% (Dr. Borenstein) That's today on Healthy Minds. 01:01.000 --> 01:04.000 position:20%,start line:79.33% size:60% Healthy Minds is brought to you in part by: 01:04.000 --> 01:09.000 position:20%,start line:79.33% size:60% The American Psychiatric Association Foundation. 01:09.000 --> 01:12.000 position:27.5%,start line:79.33% size:42.5% The Graham Boeckh Foundation. 01:14.000 --> 01:17.000 position:22.5%,start line:79.33% size:55% And the New York State Office of Mental Health. 01:21.000 --> 01:26.000 position:17.5%,start line:79.33% size:62.5% Welcome to Healthy Minds, I'm Dr. Jeff Borenstein. 01:26.000 --> 01:29.000 position:20%,start line:79.33% size:57.5% Depression is extremely common and for those who 01:29.000 --> 01:33.000 position:20%,start line:79.33% size:60% experience this illness, extremely painful. 01:33.000 --> 01:36.000 position:20%,start line:79.33% size:60% Fortunately, most people with depression who seek help 01:36.000 --> 01:40.000 position:22.5%,start line:79.33% size:52.5% respond to treatment, but some people do not. 01:40.000 --> 01:44.000 position:17.5%,start line:79.33% size:65% Today I speak with leading researcher Dr. Lisa Pan 01:44.000 --> 01:47.000 position:30%,start line:79.33% size:40% about refractory depression and new approaches 01:47.000 --> 01:49.000 position:37.5%,start line:79.33% size:25% to helping people who do not get 01:49.000 --> 01:52.000 position:22.5%,start line:79.33% size:52.5% better with the usual medicines and therapy. 01:55.000 --> 01:56.000 position:57.5%,start line:84.66% size:32.5% Lisa welcome. 01:56.000 --> 01:57.000 position:10%,start line:84.66% size:25% Thank you. 01:57.000 --> 01:58.000 position:32.5%,start line:79.33% size:32.5% Thank you for joining us today. 01:58.000 --> 01:59.000 position:27.5%,start line:79.33% size:42.5% Thank you so much for having me here. 01:59.000 --> 02:00.000 position:30%,start line:84.66% size:40% I appreciate it. 02:00.000 --> 02:04.000 position:22.5%,start line:10% size:52.5% Your work has focused on depression and in 02:04.000 --> 02:08.000 position:20%,start line:10% size:57.5% particular what we call refractory depression. 02:08.000 --> 02:11.000 position:22.5%,start line:79.33% size:55% I'd like you to define what refractory depression is. 02:11.000 --> 02:13.000 position:25%,start line:79.33% size:47.5% So I think the most important thing to know is 02:13.000 --> 02:15.000 position:22.5%,start line:79.33% size:52.5% that depression isn't just regular sadness. 02:15.000 --> 02:17.000 position:20%,start line:10% size:57.5% So somebody who's never had depression, 02:17.000 --> 02:22.000 position:12.5%,start line:10% size:72.5% probably can't understand the severity of the low mood. 02:22.000 --> 02:24.000 position:20%,start line:79.33% size:60% And we look for symptoms in depression that include 02:24.000 --> 02:28.000 position:17.5%,start line:79.33% size:65% this, this deep sadness or - some people describe 02:28.000 --> 02:33.000 position:20%,start line:79.33% size:60% even emotionless or like it sad, a sadness that's 02:33.000 --> 02:34.000 position:25%,start line:84.66% size:47.5% almost destructive. 02:34.000 --> 02:38.000 position:10%,start line:79.33% size:80% And then also low energy levels, not being able to 02:38.000 --> 02:40.000 position:32.5%,start line:79.33% size:35% enjoy anything that you used to. 02:40.000 --> 02:43.000 position:20%,start line:79.33% size:57.5% And I mean like we call it anhedonia and it's an 02:43.000 --> 02:47.000 position:10%,start line:79.33% size:80% inability to enjoy other people, activities that you love, 02:47.000 --> 02:48.000 position:27.5%,start line:84.66% size:45% even basic things. 02:48.000 --> 02:53.000 position:15%,start line:79.33% size:67.5% And then we also see guilt, inappropriate guilt, 02:53.000 --> 02:55.000 position:10%,start line:79.33% size:77.5% about things that really aren't the person's fault. 02:55.000 --> 02:56.000 position:35%,start line:79.33% size:30% Hopelessness about the future. 02:56.000 --> 02:59.000 position:22.5%,start line:79.33% size:52.5% So people with a very severe depression will 02:59.000 --> 03:01.000 position:20%,start line:79.33% size:60% think that everything in the past was worthless. 03:01.000 --> 03:03.000 position:22.5%,start line:79.33% size:55% What's going on now is worthless and there's no 03:03.000 --> 03:05.000 position:25%,start line:79.33% size:50% hope for anything of value in the future. 03:05.000 --> 03:10.000 position:17.5%,start line:79.33% size:65% Also we'll see things like low self-esteem and then 03:10.000 --> 03:12.000 position:20%,start line:79.33% size:57.5% what can be really life threatening is thoughts 03:12.000 --> 03:15.000 position:20%,start line:79.33% size:60% about death and thoughts about suicide which can be 03:15.000 --> 03:18.000 position:22.5%,start line:79.33% size:52.5% pervasive because the depression is so severe. 03:18.000 --> 03:22.000 position:10%,start line:79.33% size:80% And the frequency of depression, what are the statistics 03:22.000 --> 03:24.000 position:17.5%,start line:79.33% size:62.5% about that because it's a very common illness. 03:24.000 --> 03:27.000 position:17.5%,start line:79.33% size:65% And so it's estimated that 5% of the population at 03:27.000 --> 03:29.000 position:32.5%,start line:79.33% size:35% any given time has depression. 03:29.000 --> 03:32.000 position:10%,start line:79.33% size:77.5% 25% of the population will have it at some time in their life. 03:32.000 --> 03:35.000 position:22.5%,start line:79.33% size:55% The population that we have been most interested in 03:35.000 --> 03:38.000 position:15%,start line:79.33% size:70% are treatment refractory and about 15% of patients 03:38.000 --> 03:41.000 position:17.5%,start line:79.33% size:65% won't respond to available treatments for depression. 03:41.000 --> 03:44.000 position:25%,start line:79.33% size:50% Treatment refractory depression affects about, 03:44.000 --> 03:46.000 position:27.5%,start line:79.33% size:42.5% estimates are 15% of people that have 03:46.000 --> 03:50.000 position:22.5%,start line:79.33% size:55% depression and that is defined in a variety of ways. 03:50.000 --> 03:53.000 position:20%,start line:79.33% size:60% We define that as having three full dose, 03:53.000 --> 03:54.000 position:20%,start line:79.33% size:60% full duration medication treatments 03:54.000 --> 03:56.000 position:15%,start line:84.66% size:67.5% that there was no response. 03:56.000 --> 04:00.000 position:27.5%,start line:79.33% size:45% So people came for treatment were given 04:00.000 --> 04:02.000 position:17.5%,start line:79.33% size:62.5% appropriate medication at a full dose for a 04:02.000 --> 04:05.000 position:15%,start line:79.33% size:70% full period of time that one would expect them to respond. 04:05.000 --> 04:06.000 position:10%,start line:84.66% size:15% Right. 04:06.000 --> 04:08.000 position:52.5%,start line:79.33% size:37.5% And they didn't respond. 04:08.000 --> 04:09.000 position:47.5%,start line:79.33% size:42.5% And that happened three times. 04:09.000 --> 04:10.000 position:10%,start line:84.66% size:15% Right. 04:10.000 --> 04:11.000 position:20%,start line:79.33% size:57.5% And the majority of the people in our study 04:11.000 --> 04:15.000 position:17.5%,start line:79.33% size:65% honestly have had far more than three treatments. 04:15.000 --> 04:19.000 position:17.5%,start line:79.33% size:62.5% I think what has been the most concerning for me is 04:19.000 --> 04:22.000 position:20%,start line:79.33% size:57.5% how this is really life threatening and that, 04:22.000 --> 04:25.000 position:12.5%,start line:79.33% size:75% you know, we, we have a couple issues that interfere in 04:25.000 --> 04:27.000 position:32.5%,start line:79.33% size:35% the ability to treat depression. 04:27.000 --> 04:30.000 position:22.5%,start line:79.33% size:52.5% One is stigma so that people don't come forward 04:30.000 --> 04:31.000 position:27.5%,start line:84.66% size:42.5% to get treatment. 04:31.000 --> 04:33.000 position:20%,start line:79.33% size:57.5% The second is a lack of understanding of the fact 04:33.000 --> 04:35.000 position:22.5%,start line:79.33% size:55% that this is a medical condition and requires 04:35.000 --> 04:36.000 position:27.5%,start line:84.66% size:45% medical treatment. 04:36.000 --> 04:40.000 position:17.5%,start line:79.33% size:65% And then I think the third thing is that because the 04:40.000 --> 04:43.000 position:20%,start line:79.33% size:60% people are hopeless you, there's really not a lot 04:43.000 --> 04:45.000 position:32.5%,start line:79.33% size:32.5% of motivation to get better. 04:45.000 --> 04:47.000 position:27.5%,start line:79.33% size:45% You really need an advocate and a treatment 04:47.000 --> 04:50.000 position:17.5%,start line:79.33% size:62.5% team that's going to push you forward and make sure 04:50.000 --> 04:51.000 position:25%,start line:79.33% size:47.5% that you're getting what you need. 04:51.000 --> 04:54.000 position:17.5%,start line:79.33% size:62.5% And so this is an illness that by its very nature 04:54.000 --> 04:56.000 position:30%,start line:79.33% size:37.5% makes it harder to treat it. 04:56.000 --> 04:58.000 position:27.5%,start line:79.33% size:45% What we do now for treatment refractory 04:58.000 --> 05:00.000 position:17.5%,start line:79.33% size:65% depression are things like ketamine treatment, 05:00.000 --> 05:04.000 position:20%,start line:79.33% size:60% vagus nerve stimulators, electroconvulsive therapy 05:04.000 --> 05:06.000 position:22.5%,start line:79.33% size:52.5% is our most effective treatment for depression 05:06.000 --> 05:08.000 position:20%,start line:79.33% size:60% and many of the patients in the study have had these. 05:08.000 --> 05:12.000 position:20%,start line:79.33% size:57.5% So people have not only not responded to the usual 05:12.000 --> 05:15.000 position:22.5%,start line:79.33% size:55% treatments they've had some treatments such as 05:15.000 --> 05:18.000 position:27.5%,start line:79.33% size:42.5% electroconvulsive treatment, some more 05:18.000 --> 05:21.000 position:20%,start line:79.33% size:57.5% experimental treatments such as ketamine which is 05:21.000 --> 05:23.000 position:50%,start line:79.33% size:35% a rapid acting anti-depressant and 05:23.000 --> 05:26.000 position:35%,start line:79.33% size:55% haven't responded even to those treatments. 05:26.000 --> 05:27.000 position:65%,start line:84.66% size:25% And then-- 05:27.000 --> 05:28.000 position:10%,start line:84.66% size:25% And then-- 05:28.000 --> 05:28.000 position:50%,start line:84.66% size:40% -- what happens? 05:28.000 --> 05:29.000 position:10%,start line:84.66% size:35% -- come to me. 05:29.000 --> 05:30.000 position:85%,start line:84.66% size:5% Ok 05:30.000 --> 05:32.000 position:17.5%,start line:79.33% size:65% And the reason why I think that we're studying that 05:32.000 --> 05:35.000 position:17.5%,start line:79.33% size:65% population that's had such severe illness and has not 05:35.000 --> 05:38.000 position:22.5%,start line:79.33% size:52.5% responded is that the disorders we're finding 05:38.000 --> 05:41.000 position:27.5%,start line:79.33% size:42.5% are related to an inability to either 05:41.000 --> 05:45.000 position:25%,start line:79.33% size:50% metabolize important molecules and chemicals in 05:45.000 --> 05:48.000 position:15%,start line:79.33% size:67.5% the body or an inability to generate neurotransmitters. 05:48.000 --> 05:50.000 position:25%,start line:79.33% size:47.5% So we have a lot of effective treatments for 05:50.000 --> 05:52.000 position:22.5%,start line:79.33% size:55% moderate depression or even severe depression 05:52.000 --> 05:54.000 position:25%,start line:79.33% size:50% that's not treatment refractory. 05:54.000 --> 05:57.000 position:25%,start line:79.33% size:47.5% But what I think is happening and this is, you know, 05:57.000 --> 05:59.000 position:25%,start line:79.33% size:47.5% based on the little bit of work I've done so far, 05:59.000 --> 06:02.000 position:10%,start line:79.33% size:80% is that if you're not generating neurotransmitters, 06:02.000 --> 06:04.000 position:20%,start line:79.33% size:60% blocking the reuptake to increase their levels is not 06:04.000 --> 06:07.000 position:12.5%,start line:79.33% size:75% going to be effective and that may be part of the reason 06:07.000 --> 06:08.000 position:22.5%,start line:79.33% size:52.5% we're seeing patients that aren't 06:08.000 --> 06:10.000 position:22.5%,start line:79.33% size:55% responding to multiple medication trials. 06:10.000 --> 06:13.000 position:22.5%,start line:79.33% size:55% So one of our forms of treatment is to try to 06:13.000 --> 06:15.000 position:27.5%,start line:79.33% size:45% increase a certain neurochemical or 06:15.000 --> 06:18.000 position:17.5%,start line:79.33% size:65% neurochemicals by blocking how much it's taken back 06:18.000 --> 06:21.000 position:27.5%,start line:79.33% size:45% up into the neuron that sends it out. 06:21.000 --> 06:22.000 position:10%,start line:84.66% size:20% Exactly. 06:22.000 --> 06:24.000 position:25%,start line:79.33% size:65% But if we're not, if we're not producing enough of 06:24.000 --> 06:28.000 position:25%,start line:79.33% size:65% that due to some metabolic kind of issue then that 06:28.000 --> 06:30.000 position:17.5%,start line:79.33% size:62.5% form of treatment may not be why it's not effective 06:30.000 --> 06:32.000 position:27.5%,start line:84.66% size:42.5% for those people. 06:32.000 --> 06:34.000 position:10%,start line:79.33% size:80% And that's what we're finding in this patient population 06:34.000 --> 06:36.000 position:40%,start line:79.33% size:20% is we're working backwards from the 06:36.000 --> 06:41.000 position:10%,start line:79.33% size:77.5% end metabolite in a biochemical pathway and trying to 06:41.000 --> 06:42.000 position:17.5%,start line:84.66% size:62.5% determine based on what's 06:42.000 --> 06:44.000 position:20%,start line:79.33% size:60% missing what needs to be replaced. 06:44.000 --> 06:47.000 position:17.5%,start line:79.33% size:62.5% And so that's the core of what we're doing with this 06:47.000 --> 06:50.000 position:20%,start line:79.33% size:60% metabolomic study is, is working backwards to see 06:50.000 --> 06:53.000 position:22.5%,start line:79.33% size:55% if there are metabolic pathways that are affected 06:53.000 --> 06:56.000 position:17.5%,start line:79.33% size:65% either from primary causes or secondary causes. 06:56.000 --> 07:00.000 position:12.5%,start line:79.33% size:75% So a primary cause would be an inheritable inborn metabolism, 07:00.000 --> 07:03.000 position:17.5%,start line:79.33% size:65% a secondary cause might be some environmental insult 07:03.000 --> 07:06.000 position:20%,start line:79.33% size:57.5% that we're not aware of but by replacing what's 07:06.000 --> 07:08.000 position:25%,start line:79.33% size:50% missing we're seeing some improvement. 07:08.000 --> 07:11.000 position:20%,start line:79.33% size:60% Now how do you determine that somebody is missing 07:11.000 --> 07:13.000 position:17.5%,start line:84.66% size:62.5% one of these metabolites. 07:13.000 --> 07:16.000 position:17.5%,start line:79.33% size:62.5% So this study we do right now does a very broad 07:16.000 --> 07:18.000 position:27.5%,start line:79.33% size:42.5% based approach to metabolic disease where we 07:18.000 --> 07:21.000 position:17.5%,start line:79.33% size:62.5% look at blood, urine, and the most important thing 07:21.000 --> 07:22.000 position:20%,start line:84.66% size:57.5% is cerebrospinal fluid. 07:22.000 --> 07:24.000 position:17.5%,start line:79.33% size:65% So we actually do a lumbar puncture to collect 07:24.000 --> 07:27.000 position:20%,start line:79.33% size:60% cerebrospinal fluid from the central nervous system 07:27.000 --> 07:32.000 position:22.5%,start line:79.33% size:52.5% and look at chemicals in that CSF sample. 07:32.000 --> 07:35.000 position:37.5%,start line:79.33% size:25% We look at neurotransmitter metabolites, 07:35.000 --> 07:37.000 position:37.5%,start line:79.33% size:25% markers of vitamin metabolism and a 07:37.000 --> 07:40.000 position:22.5%,start line:79.33% size:52.5% small molecule called tetrahydrobiopterin which 07:40.000 --> 07:42.000 position:27.5%,start line:79.33% size:45% is crucial to make neurotransmitters, 07:42.000 --> 07:46.000 position:12.5%,start line:79.33% size:75% pain modulators, and melatonin which regulates sleep. 07:46.000 --> 07:49.000 position:20%,start line:79.33% size:60% And so if that's missing it affects all those pathways. 07:49.000 --> 07:53.000 position:17.5%,start line:79.33% size:62.5% So what types of findings have you had in this, 07:53.000 --> 07:55.000 position:25%,start line:79.33% size:50% in this research and clinical work? 07:55.000 --> 07:57.000 position:17.5%,start line:79.33% size:62.5% So if it's ok I'll talk a little bit about the first 07:57.000 --> 07:58.000 position:10%,start line:84.66% size:32.5% patient who-- 07:58.000 --> 08:00.000 position:65%,start line:84.66% size:25% --Perfect. 08:00.000 --> 08:02.000 position:10%,start line:79.33% size:67.5% So that just to explain why we started doing this. 08:02.000 --> 08:05.000 position:15%,start line:79.33% size:67.5% So I had a young man and I, he's given permission 08:05.000 --> 08:08.000 position:20%,start line:79.33% size:57.5% to discuss his care and we actually published his 08:08.000 --> 08:12.000 position:22.5%,start line:79.33% size:55% case so that he, other people could be helped. 08:12.000 --> 08:16.000 position:22.5%,start line:79.33% size:52.5% So he came to us as a tertiary referral because 08:16.000 --> 08:18.000 position:20%,start line:79.33% size:57.5% of significant suicidal behavior and depression 08:18.000 --> 08:20.000 position:20%,start line:79.33% size:57.5% that was not responding to treatment. 08:20.000 --> 08:23.000 position:22.5%,start line:79.33% size:52.5% And what had happened is that we had tried 08:23.000 --> 08:26.000 position:17.5%,start line:79.33% size:65% literally every medication available, we'd even done 08:26.000 --> 08:29.000 position:20%,start line:79.33% size:60% experimental medications like you talked about 08:29.000 --> 08:32.000 position:20%,start line:79.33% size:60% including a medicine for Lou Gehrig's disease 08:32.000 --> 08:34.000 position:17.5%,start line:79.33% size:62.5% that's shown some promise in anxiety and depression 08:34.000 --> 08:35.000 position:22.5%,start line:84.66% size:52.5% and nothing happened. 08:35.000 --> 08:38.000 position:27.5%,start line:79.33% size:45% And in fact at the time that we made this discovery 08:38.000 --> 08:41.000 position:35%,start line:79.33% size:30% he was in an inpatient psychiatric facility, 08:41.000 --> 08:44.000 position:25%,start line:79.33% size:47.5% horribly depressed, on 17 medications 08:44.000 --> 08:47.000 position:32.5%,start line:79.33% size:35% just to try to keep him safe and he was 08:47.000 --> 08:49.000 position:10%,start line:79.33% size:80% not having a response nor was he really having side effects 08:49.000 --> 08:51.000 position:32.5%,start line:79.33% size:35% so I had never seen anything like that. 08:51.000 --> 08:53.000 position:22.5%,start line:79.33% size:55% It was like we weren't doing anything. 08:53.000 --> 08:56.000 position:25%,start line:79.33% size:50% He was trying to end his life on the unit. 08:56.000 --> 09:00.000 position:27.5%,start line:79.33% size:45% And so I went to a biochemical geneticist who 09:00.000 --> 09:04.000 position:25%,start line:79.33% size:50% had trained me named David Finegold and I said 09:04.000 --> 09:06.000 position:12.5%,start line:79.33% size:75% there was a study in the 1980s that National Institutes 09:06.000 --> 09:09.000 position:22.5%,start line:79.33% size:55% of Health showing that patients who had severe 09:09.000 --> 09:12.000 position:25%,start line:79.33% size:47.5% near lethal suicide attempts had low 09:12.000 --> 09:16.000 position:17.5%,start line:79.33% size:65% 5-hydroxyindoleacetic acid in their central nervous system, 09:16.000 --> 09:19.000 position:25%,start line:79.33% size:47.5% in the CSF samples, cerebrospinal fluid. 09:19.000 --> 09:22.000 position:17.5%,start line:79.33% size:62.5% And I asked him "Is there any way you can tell me 09:22.000 --> 09:24.000 position:25%,start line:79.33% size:47.5% "anything about his neurotransmitter profile 09:24.000 --> 09:26.000 position:22.5%,start line:79.33% size:55% so I have some idea of what's going on here." 09:26.000 --> 09:28.000 position:27.5%,start line:79.33% size:42.5% And he said to me "I can do better than that. 09:28.000 --> 09:30.000 position:22.5%,start line:79.33% size:52.5% "We can run the whole neurologic panel that we do 09:30.000 --> 09:34.000 position:22.5%,start line:10% size:52.5% "for seizure, and you know neurodegenerative disease", 09:34.000 --> 09:36.000 position:30%,start line:10% size:37.5% and when he did that he found this missing 09:36.000 --> 09:38.000 position:32.5%,start line:10% size:35% small molecule tetrahydrobiopterin 09:38.000 --> 09:40.000 position:22.5%,start line:10% size:52.5% it's also called BH4. 09:40.000 --> 09:42.000 position:35%,start line:84.66% size:27.5% It was low. 09:42.000 --> 09:46.000 position:17.5%,start line:79.33% size:62.5% So the range starts at 10 and his was at 9 which 09:46.000 --> 09:49.000 position:20%,start line:79.33% size:60% doesn't sound ridiculous but it's a big difference 09:49.000 --> 09:52.000 position:20%,start line:79.33% size:57.5% because a young healthy person should be in the 09:52.000 --> 09:54.000 position:27.5%,start line:79.33% size:42.5% middle to the top end of that range. 09:54.000 --> 09:58.000 position:20%,start line:79.33% size:60% And what was fascinating is that they make this molecule 09:58.000 --> 10:02.000 position:10%,start line:79.33% size:77.5% to treat another disease called phenylketonuria. 10:02.000 --> 10:04.000 position:17.5%,start line:79.33% size:62.5% And so we repurposed this molecule and gave it to 10:04.000 --> 10:07.000 position:27.5%,start line:79.33% size:45% him and we started seeing improvement. 10:07.000 --> 10:09.000 position:30%,start line:79.33% size:37.5% And we saw some fascinating changes which made 10:09.000 --> 10:12.000 position:12.5%,start line:79.33% size:72.5% me really feel like we had to keep looking for other people. 10:12.000 --> 10:16.000 position:20%,start line:79.33% size:60% In the first eight weeks he landscaped his mother's yard. 10:16.000 --> 10:19.000 position:32.5%,start line:79.33% size:32.5% He was having inappropriate feelings of 10:19.000 --> 10:21.000 position:25%,start line:79.33% size:47.5% love towards people on the phone. 10:21.000 --> 10:25.000 position:17.5%,start line:79.33% size:62.5% Very bizarre changes that he was describing as bizarre. 10:25.000 --> 10:29.000 position:20%,start line:79.33% size:57.5% And so I knew something was happening and what was 10:29.000 --> 10:31.000 position:22.5%,start line:79.33% size:55% fascinating is that as this progressed he's now 10:31.000 --> 10:36.000 position:20%,start line:79.33% size:57.5% four years healthy, I'm sorry five years healthy, 10:36.000 --> 10:39.000 position:20%,start line:79.33% size:57.5% and with no psychiatric medication just with this 10:39.000 --> 10:40.000 position:22.5%,start line:84.66% size:52.5% replacement molecule. 10:40.000 --> 10:44.000 position:17.5%,start line:79.33% size:65% And so when I saw that my, my whole career changed. 10:44.000 --> 10:47.000 position:22.5%,start line:79.33% size:52.5% So I work in a clinic started by Dr. David Brent 10:47.000 --> 10:50.000 position:17.5%,start line:79.33% size:62.5% that is a-- it's services for teens at risk. 10:50.000 --> 10:53.000 position:17.5%,start line:79.33% size:62.5% And that we specialize in suicide prevention 10:53.000 --> 10:54.000 position:30%,start line:84.66% size:37.5% and depression. 10:54.000 --> 10:56.000 position:20%,start line:79.33% size:60% And so I started looking at the patients I had that 10:56.000 --> 10:58.000 position:25%,start line:84.66% size:47.5% were not improving. 10:58.000 --> 10:59.000 position:27.5%,start line:79.33% size:45% And the next three patients we tested also 10:59.000 --> 11:01.000 position:17.5%,start line:84.66% size:62.5% had a metabolic disorder. 11:01.000 --> 11:04.000 position:12.5%,start line:79.33% size:75% And those three patients had a disorder of folate metabolism 11:04.000 --> 11:06.000 position:30%,start line:79.33% size:37.5% so that they're folate looks totally 11:06.000 --> 11:08.000 position:22.5%,start line:79.33% size:55% normal in their blood, but when we test the central 11:08.000 --> 11:11.000 position:25%,start line:79.33% size:47.5% nervous system, the folate's not either 11:11.000 --> 11:12.000 position:20%,start line:79.33% size:57.5% crossing in the central nervous system or being 11:12.000 --> 11:15.000 position:10%,start line:79.33% size:77.5% processed appropriately so it's available to the neurons, 11:15.000 --> 11:18.000 position:20%,start line:79.33% size:57.5% and so that too affects neurotransmitter metabolism. 11:18.000 --> 11:22.000 position:10%,start line:79.33% size:80% We expected to maybe find 10% of patients had something, 11:22.000 --> 11:24.000 position:32.5%,start line:79.33% size:35% we had no idea we were going to find that 11:24.000 --> 11:26.000 position:17.5%,start line:79.33% size:65% two thirds of the patients we tested had something 11:26.000 --> 11:27.000 position:20%,start line:79.33% size:57.5% and that there would be treatments available. 11:27.000 --> 11:30.000 position:17.5%,start line:79.33% size:62.5% So of the people that you were looking at who were 11:30.000 --> 11:33.000 position:22.5%,start line:79.33% size:52.5% these people who have refractory depression not 11:33.000 --> 11:36.000 position:20%,start line:79.33% size:57.5% responding to the usual treatments and maybe other 11:36.000 --> 11:40.000 position:22.5%,start line:79.33% size:55% treatments, two thirds had, you were able to find, 11:40.000 --> 11:43.000 position:27.5%,start line:79.33% size:45% had some metabolic issue that could be corrected. 11:43.000 --> 11:45.000 position:45%,start line:84.66% size:10% Yes. 11:45.000 --> 11:47.000 position:17.5%,start line:79.33% size:65% And we're just now, as the study is expanding, 11:47.000 --> 11:49.000 position:17.5%,start line:79.33% size:65% we're just now starting to bring people back. 11:49.000 --> 11:52.000 position:30%,start line:79.33% size:37.5% We refer out to geneticists to treat and 11:52.000 --> 11:54.000 position:17.5%,start line:79.33% size:65% then we bring them back to follow up so I'm hoping 11:54.000 --> 11:57.000 position:17.5%,start line:79.33% size:65% we'll have more data about how many people have responded 11:57.000 --> 11:59.000 position:30%,start line:79.33% size:40% but so far we've had some improvement in 11:59.000 --> 12:00.000 position:32.5%,start line:79.33% size:32.5% everyone that we've followed up. 12:00.000 --> 12:04.000 position:25%,start line:79.33% size:65% Could you tell us a little bit more about some of the 12:04.000 --> 12:07.000 position:25%,start line:79.33% size:65% metabolic deficiencies and changes that you've 12:07.000 --> 12:08.000 position:52.5%,start line:84.66% size:37.5% seen in people. 12:08.000 --> 12:11.000 position:20%,start line:79.33% size:60% So the first one that we found is a disorder of 12:11.000 --> 12:14.000 position:20%,start line:79.33% size:57.5% tetrahydrobiopterin and there are a couple of 12:14.000 --> 12:16.000 position:22.5%,start line:79.33% size:55% different ways you can get a tetrahydrobiopterin 12:16.000 --> 12:19.000 position:22.5%,start line:79.33% size:55% deficiency but they're all treated the same. 12:19.000 --> 12:22.000 position:22.5%,start line:79.33% size:55% And that is, that is a small molecule in the 12:22.000 --> 12:23.000 position:20%,start line:84.66% size:57.5% central nervous system. 12:23.000 --> 12:25.000 position:37.5%,start line:79.33% size:22.5% We find a deficiency from the 12:25.000 --> 12:27.000 position:15%,start line:79.33% size:67.5% cerebrospinal fluid testing that we do. 12:27.000 --> 12:30.000 position:27.5%,start line:79.33% size:45% And then there's a replacement therapy for that. 12:30.000 --> 12:31.000 position:20%,start line:79.33% size:57.5% I think the reason that one has been one of the 12:31.000 --> 12:36.000 position:17.5%,start line:79.33% size:62.5% most severe presentations in phenotype is that it's 12:36.000 --> 12:40.000 position:20%,start line:79.33% size:60% required, that molecules required to make serotonin, 12:40.000 --> 12:45.000 position:17.5%,start line:79.33% size:65% dopamine, pain modulators, and also melatonin 12:45.000 --> 12:49.000 position:22.5%,start line:79.33% size:52.5% it helps regulate the body's function. 12:49.000 --> 12:52.000 position:10%,start line:79.33% size:77.5% Furthermore it can affect white matter and neuronal structure. 12:52.000 --> 12:56.000 position:10%,start line:79.33% size:77.5% So that that can have a drastic effect on brain function. 12:56.000 --> 12:58.000 position:35%,start line:79.33% size:50% So not having it not really affects the brain 12:58.000 --> 13:00.000 position:55%,start line:79.33% size:35% in a multitude of ways. 13:00.000 --> 13:01.000 position:10%,start line:84.66% size:10% Yes. 13:01.000 --> 13:02.000 position:17.5%,start line:79.33% size:62.5% The second disorder which is the most common one we 13:02.000 --> 13:05.000 position:20%,start line:79.33% size:60% found is called cerebral folate deficiency. 13:05.000 --> 13:08.000 position:20%,start line:79.33% size:60% That's defined as having normal circulating folate 13:08.000 --> 13:11.000 position:17.5%,start line:79.33% size:65% in the blood but deficient folate in the central 13:11.000 --> 13:13.000 position:20%,start line:79.33% size:60% nervous system and again we find that through 13:13.000 --> 13:15.000 position:25%,start line:79.33% size:47.5% cerebrospinal fluid testing. 13:15.000 --> 13:18.000 position:17.5%,start line:79.33% size:65% Again this is very crucial to neurotransmitter metabolism. 13:18.000 --> 13:21.000 position:27.5%,start line:79.33% size:45% The folate pathway directly interacts with 13:21.000 --> 13:24.000 position:22.5%,start line:79.33% size:52.5% amino acid metabolism and the generation of 13:24.000 --> 13:27.000 position:20%,start line:79.33% size:57.5% serotonin and dopamine, and so there's a clear 13:27.000 --> 13:29.000 position:27.5%,start line:79.33% size:45% biochemical reason for depression. 13:29.000 --> 13:31.000 position:30%,start line:79.33% size:40% And again in the neurologic forms of 13:31.000 --> 13:33.000 position:30%,start line:79.33% size:37.5% cerebral folate deficiency, we actually 13:33.000 --> 13:35.000 position:20%,start line:79.33% size:60% see visible white matter changes on MRI. 13:35.000 --> 13:37.000 position:25%,start line:79.33% size:50% So we know there's a structural component to 13:37.000 --> 13:40.000 position:17.5%,start line:79.33% size:62.5% not having folate present the central nervous system 13:40.000 --> 13:43.000 position:22.5%,start line:79.33% size:52.5% that can affect white matter, the myelin that 13:43.000 --> 13:46.000 position:25%,start line:79.33% size:50% covers the brain and protects the brain and 13:46.000 --> 13:49.000 position:17.5%,start line:79.33% size:62.5% allows for communication, and also the neuron itself 13:49.000 --> 13:51.000 position:20%,start line:79.33% size:57.5% the axons of the neuron can be affected by 13:51.000 --> 13:53.000 position:20%,start line:84.66% size:60% having deficient folate. 13:53.000 --> 13:55.000 position:27.5%,start line:79.33% size:62.5% And with deficient folate there's also an ability to 13:55.000 --> 13:58.000 position:45%,start line:79.33% size:45% give medicine that can remediate that. 13:58.000 --> 14:00.000 position:10%,start line:79.33% size:62.5% Exactly so we give a form of folate that the body 14:00.000 --> 14:03.000 position:25%,start line:79.33% size:47.5% doesn't have to act on for it to function. 14:03.000 --> 14:05.000 position:27.5%,start line:84.66% size:45% There's two forms. 14:05.000 --> 14:07.000 position:22.5%,start line:79.33% size:52.5% Depending on what the disorder is, 14:07.000 --> 14:09.000 position:15%,start line:84.66% size:67.5% different forms are needed. 14:09.000 --> 14:11.000 position:20%,start line:79.33% size:60% What's amazing though is we know from neurologic 14:11.000 --> 14:13.000 position:20%,start line:79.33% size:57.5% studies from quite some time ago that when you 14:13.000 --> 14:17.000 position:17.5%,start line:79.33% size:65% give the folate, the white matter change is correct. 14:17.000 --> 14:20.000 position:17.5%,start line:79.33% size:65% So it's an important thing for the brain to have. 14:20.000 --> 14:22.000 position:27.5%,start line:79.33% size:42.5% And so that's the second thing we found. 14:22.000 --> 14:27.000 position:20%,start line:79.33% size:60% The third is a disorder, on a profile, a blood profile 14:27.000 --> 14:29.000 position:42.5%,start line:79.33% size:15% called acylcarnitine profiling. 14:29.000 --> 14:33.000 position:20%,start line:79.33% size:60% And this is, it's a hint that there's a disorder of 14:33.000 --> 14:35.000 position:27.5%,start line:84.66% size:45% energy metabolism. 14:35.000 --> 14:36.000 position:32.5%,start line:79.33% size:35% But we have to find out why. 14:36.000 --> 14:39.000 position:17.5%,start line:79.33% size:65% And so we refer to medical genetics to do further 14:39.000 --> 14:42.000 position:17.5%,start line:79.33% size:62.5% testing but some of those disorders can be treated 14:42.000 --> 14:46.000 position:20%,start line:79.33% size:57.5% with riboflavin and the person will improve. 14:46.000 --> 14:49.000 position:17.5%,start line:79.33% size:72.5% In the people who you've seen who've had these deficiencies, 14:49.000 --> 14:53.000 position:45%,start line:79.33% size:30% did the, was the depression occurring 14:53.000 --> 14:55.000 position:20%,start line:79.33% size:60% throughout their life or just started at a certain 14:55.000 --> 14:57.000 position:22.5%,start line:79.33% size:52.5% point in time and how does that relate to this 14:57.000 --> 14:59.000 position:27.5%,start line:84.66% size:42.5% deficiency issue? 14:59.000 --> 15:03.000 position:22.5%,start line:79.33% size:52.5% This is a fascinating question so I'll say first 15:03.000 --> 15:06.000 position:20%,start line:79.33% size:57.5% we have a full range in this but almost everyone 15:06.000 --> 15:08.000 position:22.5%,start line:79.33% size:55% it was early childhood or at puberty. 15:08.000 --> 15:12.000 position:22.5%,start line:79.33% size:52.5% And this is important because in, in biochemical 15:12.000 --> 15:14.000 position:20%,start line:79.33% size:57.5% genetics there are many disorders that have an 15:14.000 --> 15:17.000 position:22.5%,start line:79.33% size:55% onset at puberty or at a time of stress to the body. 15:17.000 --> 15:21.000 position:22.5%,start line:79.33% size:55% So disorders that will come on after pregnancy or 15:21.000 --> 15:23.000 position:20%,start line:79.33% size:60% disorders that will come on at puberty because of 15:23.000 --> 15:24.000 position:27.5%,start line:84.66% size:42.5% hormonal changes. 15:24.000 --> 15:26.000 position:27.5%,start line:79.33% size:45% And that's true in psychiatry also. 15:26.000 --> 15:28.000 position:22.5%,start line:79.33% size:55% And so I have wondered about the relationship 15:28.000 --> 15:31.000 position:22.5%,start line:79.33% size:52.5% between onset and the fact that these might be 15:31.000 --> 15:33.000 position:17.5%,start line:79.33% size:62.5% metabolic conditions that are contributing to the 15:33.000 --> 15:34.000 position:22.5%,start line:84.66% size:55% psychiatric phenotype. 15:34.000 --> 15:39.000 position:27.5%,start line:79.33% size:62.5% So it might be that, that sort of a storyline of 15:39.000 --> 15:43.000 position:37.5%,start line:79.33% size:40% these refractory depression people who have 15:43.000 --> 15:47.000 position:17.5%,start line:79.33% size:62.5% had who haven't responded to anything but may, 15:47.000 --> 15:50.000 position:12.5%,start line:79.33% size:75% may have a metabolic issue and may respond to that, 15:50.000 --> 15:52.000 position:20%,start line:79.33% size:60% these are people who the depression might have 15:52.000 --> 15:55.000 position:25%,start line:79.33% size:50% started in childhood and that might be an 15:55.000 --> 15:59.000 position:20%,start line:79.33% size:57.5% indication that they're at greater risk of being 15:59.000 --> 16:00.000 position:25%,start line:84.66% size:47.5% found to have this. 16:00.000 --> 16:03.000 position:10%,start line:79.33% size:57.5% Yeah, I think we have a small N but that's been 16:03.000 --> 16:05.000 position:10%,start line:79.33% size:55% true in the population we studied so far. 16:05.000 --> 16:08.000 position:27.5%,start line:79.33% size:45% For somebody who's watching at home right now, 16:08.000 --> 16:10.000 position:30%,start line:79.33% size:37.5% who either they themselves have a 16:10.000 --> 16:13.000 position:22.5%,start line:79.33% size:55% depression that hasn't respond to treatment or a 16:13.000 --> 16:17.000 position:20%,start line:79.33% size:60% loved one, family member has that, what should they do? 16:17.000 --> 16:19.000 position:25%,start line:79.33% size:47.5% I think it's really important for me to say 16:19.000 --> 16:20.000 position:27.5%,start line:79.33% size:42.5% that this is very preliminary. 16:20.000 --> 16:23.000 position:22.5%,start line:79.33% size:52.5% I think, I think it's exciting and it gives us 16:23.000 --> 16:25.000 position:17.5%,start line:79.33% size:62.5% an idea that there may be things happening we didn't 16:25.000 --> 16:27.000 position:27.5%,start line:84.66% size:45% know about before. 16:27.000 --> 16:29.000 position:20%,start line:79.33% size:60% But right now what we're desperately trying to do 16:29.000 --> 16:32.000 position:17.5%,start line:79.33% size:62.5% is find a way to test the blood so that this will be 16:32.000 --> 16:34.000 position:22.5%,start line:84.66% size:55% available to everyone. 16:34.000 --> 16:38.000 position:25%,start line:79.33% size:50% But it's so, it's in preliminary stages. 16:38.000 --> 16:42.000 position:17.5%,start line:79.33% size:62.5% We don't know really how, how well people will 16:42.000 --> 16:44.000 position:17.5%,start line:79.33% size:62.5% respond or if people that are less severe are going 16:44.000 --> 16:46.000 position:10%,start line:84.66% size:65% to have similar disorders. 16:46.000 --> 16:50.000 position:12.5%,start line:79.33% size:60% But I would say that I'd have hope because I think 16:50.000 --> 16:52.000 position:35%,start line:79.33% size:30% the field is expanding quickly. 16:52.000 --> 16:54.000 position:20%,start line:79.33% size:60% We're finding new things that maybe contributing to 16:54.000 --> 16:59.000 position:22.5%,start line:79.33% size:55% depression and so I do think there's going to be 16:59.000 --> 17:01.000 position:20%,start line:79.33% size:57.5% potentially alternative treatments available in 17:01.000 --> 17:03.000 position:35%,start line:84.66% size:27.5% the future. 17:03.000 --> 17:05.000 position:22.5%,start line:79.33% size:52.5% Should people who are experiencing 17:05.000 --> 17:10.000 position:12.5%,start line:79.33% size:75% refractory depression, sort of go for additional treatment, 17:10.000 --> 17:12.000 position:22.5%,start line:79.33% size:55% maybe more specialized treatment, maybe in an 17:12.000 --> 17:17.000 position:22.5%,start line:79.33% size:55% academic setting where perhaps they can be 17:17.000 --> 17:20.000 position:25%,start line:79.33% size:47.5% checked for some of these metabolite issues? 17:20.000 --> 17:22.000 position:20%,start line:79.33% size:60% I do think if you have a family member or if you 17:22.000 --> 17:24.000 position:22.5%,start line:79.33% size:55% yourself are, have not responded to what's 17:24.000 --> 17:26.000 position:20%,start line:79.33% size:60% available it makes sense to see what else you can 17:26.000 --> 17:28.000 position:32.5%,start line:84.66% size:35% find for sure. 17:28.000 --> 17:31.000 position:25%,start line:79.33% size:50% Where do you see the research moving as we look 17:31.000 --> 17:34.000 position:20%,start line:79.33% size:57.5% over the next few years for treating depression 17:34.000 --> 17:37.000 position:27.5%,start line:79.33% size:42.5% and in particular refractory depression? 17:37.000 --> 17:41.000 position:17.5%,start line:79.33% size:65% I'm hoping that there will be other academic centers 17:41.000 --> 17:43.000 position:20%,start line:79.33% size:60% that will replicate what we've found and if we find 17:43.000 --> 17:48.000 position:17.5%,start line:79.33% size:65% this is legitimately being present in this population 17:48.000 --> 17:50.000 position:22.5%,start line:79.33% size:52.5% that we'll find a way to streamline medical 17:50.000 --> 17:53.000 position:32.5%,start line:79.33% size:35% evaluation for these disorders. 17:53.000 --> 17:55.000 position:20%,start line:79.33% size:60% Right now this is a huge burden to the participant 17:55.000 --> 17:57.000 position:17.5%,start line:79.33% size:62.5% because they have to have a lumbar puncture and a 17:57.000 --> 17:58.000 position:27.5%,start line:84.66% size:45% lot of blood work. 17:58.000 --> 18:00.000 position:17.5%,start line:84.66% size:62.5% It's also very expensive. 18:00.000 --> 18:02.000 position:17.5%,start line:79.33% size:62.5% And so I'm hoping that as we start identifying these 18:02.000 --> 18:06.000 position:17.5%,start line:79.33% size:65% specific disorders we find ways to look for them and 18:06.000 --> 18:09.000 position:20%,start line:79.33% size:60% that this very - I think we have the tip of the 18:09.000 --> 18:11.000 position:25%,start line:79.33% size:50% iceberg here so this very early work. 18:11.000 --> 18:13.000 position:22.5%,start line:79.33% size:55% I hope it will come to fruition and we'll find 18:13.000 --> 18:16.000 position:10%,start line:79.33% size:77.5% some new things about treatment for refractory depression. 18:16.000 --> 18:18.000 position:30%,start line:79.33% size:57.5% I want to shift gears a little bit because I know 18:18.000 --> 18:22.000 position:22.5%,start line:79.33% size:62.5% you've done work in terms of suicide prevention and ask 18:22.000 --> 18:25.000 position:10%,start line:79.33% size:80% you how all of this fits in with that very important issue. 18:25.000 --> 18:30.000 position:17.5%,start line:79.33% size:65% Suicide is really what has driven most of my work 18:30.000 --> 18:32.000 position:17.5%,start line:79.33% size:62.5% because I have never seen a loss like somebody who's 18:32.000 --> 18:35.000 position:32.5%,start line:79.33% size:32.5% lost a family member to suicide. 18:35.000 --> 18:38.000 position:17.5%,start line:79.33% size:62.5% And I think that the part that I really want to 18:38.000 --> 18:41.000 position:20%,start line:79.33% size:60% communicate and - I work with a group that 18:41.000 --> 18:43.000 position:17.5%,start line:79.33% size:62.5% Sue Wesner started at the University of Pittsburgh 18:43.000 --> 18:45.000 position:25%,start line:79.33% size:50% called 'survivors of suicide' where we talked 18:45.000 --> 18:47.000 position:20%,start line:79.33% size:60% to family members who've lost a member of the 18:47.000 --> 18:49.000 position:27.5%,start line:79.33% size:42.5% family or a loved one to suicide. 18:49.000 --> 18:52.000 position:22.5%,start line:79.33% size:55% And I think the really crucial thing here is that 18:52.000 --> 18:56.000 position:10%,start line:79.33% size:77.5% we need to understand that this is a medical condition. 18:56.000 --> 18:59.000 position:17.5%,start line:79.33% size:62.5% The, the brain of someone who's completed suicide is 18:59.000 --> 19:01.000 position:30%,start line:79.33% size:40% not healthy, and so we're trying to apply, 19:01.000 --> 19:03.000 position:27.5%,start line:79.33% size:42.5% you know, healthy thought processes 19:03.000 --> 19:06.000 position:35%,start line:79.33% size:27.5% to what was happening during a 19:06.000 --> 19:09.000 position:27.5%,start line:79.33% size:45% suicide attempt or a suicide death. 19:09.000 --> 19:12.000 position:20%,start line:79.33% size:57.5% And I think it's really crucial that we understand 19:12.000 --> 19:15.000 position:17.5%,start line:79.33% size:65% that these kinds of things so, you know, biochemical 19:15.000 --> 19:16.000 position:25%,start line:79.33% size:47.5% changes that no one has any control over. 19:16.000 --> 19:19.000 position:25%,start line:10% size:47.5% You know structural changes that make a brain 19:19.000 --> 19:22.000 position:30%,start line:10% size:37.5% more likely to, to engage in suicidal 19:22.000 --> 19:26.000 position:27.5%,start line:10% size:42.5% behavior are true biologic phenomenon. 19:26.000 --> 19:31.000 position:17.5%,start line:79.33% size:65% And so when I see families grieving and nothing - 19:31.000 --> 19:34.000 position:20%,start line:79.33% size:60% that is for somebody who has died, nothing was 19:34.000 --> 19:36.000 position:20%,start line:79.33% size:60% done wrong, that this is an illness, any more than 19:36.000 --> 19:38.000 position:20%,start line:79.33% size:57.5% if somebody had a heart attack you would say well 19:38.000 --> 19:39.000 position:17.5%,start line:84.66% size:65% I could have prevented it. 19:39.000 --> 19:43.000 position:20%,start line:79.33% size:60% It's a medical condition and it's life threatening. 19:43.000 --> 19:46.000 position:12.5%,start line:79.33% size:47.5% And I do think it's crucial that, I'm not 19:46.000 --> 19:47.000 position:20%,start line:79.33% size:60% saying that this is life threatening and that 19:47.000 --> 19:50.000 position:17.5%,start line:79.33% size:65% people who have depression should not seek treatment, 19:50.000 --> 19:52.000 position:17.5%,start line:79.33% size:65% we do have good treatments for things, but what I 19:52.000 --> 19:54.000 position:20%,start line:79.33% size:57.5% want to say is that the very severe end of the spectrum 19:54.000 --> 19:56.000 position:27.5%,start line:79.33% size:42.5% this is a medical problem and we need to 19:56.000 --> 19:58.000 position:20%,start line:79.33% size:57.5% understand it better so we can take care of it. 19:58.000 --> 20:01.000 position:42.5%,start line:79.33% size:47.5% I think it's a very important point for 20:01.000 --> 20:05.000 position:25%,start line:79.33% size:55% survivors to know that they didn't do anything wrong. 20:05.000 --> 20:07.000 position:37.5%,start line:84.66% size:52.5% Their loved one had-- 20:07.000 --> 20:07.000 position:10%,start line:84.66% size:32.5% -- an illness 20:07.000 --> 20:09.000 position:57.5%,start line:84.66% size:32.5% --an illness. 20:09.000 --> 20:12.000 position:30%,start line:79.33% size:60% And while most illnesses are treatable, 20:12.000 --> 20:16.000 position:27.5%,start line:79.33% size:45% sometimes it isn't successfully treated. 20:16.000 --> 20:18.000 position:27.5%,start line:79.33% size:45% And then the other important message is that 20:18.000 --> 20:21.000 position:22.5%,start line:79.33% size:52.5% if somebody is having thoughts of hurting themself 20:21.000 --> 20:24.000 position:35%,start line:79.33% size:27.5% they should immediately seek treatment. 20:24.000 --> 20:26.000 position:10%,start line:84.66% size:15% Right. 20:26.000 --> 20:27.000 position:22.5%,start line:79.33% size:42.5% Because there are things we can do, exactly. 20:27.000 --> 20:29.000 position:25%,start line:79.33% size:47.5% It's a chronic life threatening illness and 20:29.000 --> 20:31.000 position:22.5%,start line:79.33% size:52.5% you definitely should have treatment for it. 20:31.000 --> 20:35.000 position:20%,start line:79.33% size:57.5% I'm curious about going back to the first patient 20:35.000 --> 20:37.000 position:20%,start line:84.66% size:57.5% who was helped by this. 20:37.000 --> 20:41.000 position:10%,start line:79.33% size:80% Tell me how his life has changed as a result of the treatment. 20:41.000 --> 20:44.000 position:25%,start line:79.33% size:50% So when I was taking care of him he was being 20:44.000 --> 20:46.000 position:20%,start line:79.33% size:57.5% repeatedly hospitalized so much that he couldn't 20:46.000 --> 20:47.000 position:25%,start line:84.66% size:47.5% attend high school. 20:47.000 --> 20:50.000 position:25%,start line:79.33% size:47.5% And when he started responding to the 20:50.000 --> 20:53.000 position:17.5%,start line:79.33% size:65% replacement therapy he was able to graduate and he 20:53.000 --> 20:55.000 position:10%,start line:79.33% size:47.5% went to college and he's actually an 20:55.000 --> 20:58.000 position:10%,start line:79.33% size:77.5% environmental scientist now and he's in a healthy relationship 20:58.000 --> 21:00.000 position:30%,start line:84.66% size:37.5% and he's happy. 21:00.000 --> 21:02.000 position:12.5%,start line:79.33% size:75% There are days that depression will still be present 21:02.000 --> 21:06.000 position:22.5%,start line:79.33% size:52.5% but nothing like what he came from. 21:06.000 --> 21:11.000 position:20%,start line:79.33% size:57.5% And he talks about, you know, trying to learn how, 21:11.000 --> 21:13.000 position:22.5%,start line:79.33% size:55% how to live because he had never planned to get 21:13.000 --> 21:16.000 position:22.5%,start line:84.66% size:52.5% beyond the age of 20. 21:16.000 --> 21:21.000 position:22.5%,start line:79.33% size:55% And so it was really a fascinating change to watch. 21:21.000 --> 21:22.000 position:22.5%,start line:79.33% size:52.5% And I've seen it with other patients too. 21:22.000 --> 21:25.000 position:10%,start line:79.33% size:65% We had another young woman with the same disorder who 21:25.000 --> 21:28.000 position:12.5%,start line:79.33% size:50% had a second medical illness that was life 21:28.000 --> 21:31.000 position:17.5%,start line:79.33% size:62.5% threatening and she would allow that medical illness 21:31.000 --> 21:34.000 position:12.5%,start line:79.33% size:72.5% to get out of control because she didn't want to be alive. 21:34.000 --> 21:37.000 position:17.5%,start line:79.33% size:62.5% And so she has also shown significant improvement 21:37.000 --> 21:39.000 position:25%,start line:79.33% size:50% and being able to go to college which was 21:39.000 --> 21:43.000 position:17.5%,start line:79.33% size:62.5% something I think she and her family didn't expect. 21:43.000 --> 21:45.000 position:32.5%,start line:79.33% size:57.5% So basically people are able to have their life 21:45.000 --> 21:48.000 position:50%,start line:79.33% size:40% back as a result of this. 21:48.000 --> 21:51.000 position:20%,start line:79.33% size:60% And it's been, it's been really challenging because 21:51.000 --> 21:54.000 position:20%,start line:79.33% size:57.5% we have patients coming to us on referral for the 21:54.000 --> 21:59.000 position:20%,start line:79.33% size:57.5% study and, you know, we just with, with some 21:59.000 --> 22:01.000 position:27.5%,start line:79.33% size:45% private funds, I'm incredibly thankful for 22:01.000 --> 22:04.000 position:17.5%,start line:79.33% size:62.5% the funding we have - the Children's Hospital Foundation 22:04.000 --> 22:07.000 position:22.5%,start line:79.33% size:55% and an anonymous donor has given us funds, 22:07.000 --> 22:08.000 position:32.5%,start line:79.33% size:32.5% and with some private funds we've been 22:08.000 --> 22:10.000 position:32.5%,start line:79.33% size:32.5% able to study young adults. 22:10.000 --> 22:13.000 position:20%,start line:79.33% size:60% But I just had a 70 year old man come to the study 22:13.000 --> 22:15.000 position:17.5%,start line:79.33% size:62.5% who has been ill since he was eight years old and he's 22:15.000 --> 22:18.000 position:17.5%,start line:79.33% size:62.5% asking me like "if I have one of these disorders." 22:18.000 --> 22:21.000 position:25%,start line:79.33% size:50% And his profile fits exactly what we see. 22:21.000 --> 22:23.000 position:17.5%,start line:79.33% size:65% "You know I'd like to have another I'd like to have 22:23.000 --> 22:24.000 position:15%,start line:84.66% size:67.5% "10 years where I feel OK." 22:24.000 --> 22:26.000 position:22.5%,start line:79.33% size:55% And it's heartbreaking you know. 22:26.000 --> 22:30.000 position:20%,start line:79.33% size:60% It really is devastating when depression is 22:30.000 --> 22:33.000 position:30%,start line:79.33% size:40% untreated or not successfully treated. 22:33.000 --> 22:36.000 position:17.5%,start line:79.33% size:65% I think an important point is while you are focusing 22:36.000 --> 22:39.000 position:25%,start line:79.33% size:47.5% on that 15% to have refractory depression-- 22:39.000 --> 22:39.000 position:10%,start line:79.33% size:30% there are so many more. 22:39.000 --> 22:41.000 position:70%,start line:84.66% size:20% --Right. 22:41.000 --> 22:44.000 position:35%,start line:79.33% size:52.5% And the vast majority of people do respond to 22:44.000 --> 22:47.000 position:32.5%,start line:79.33% size:47.5% current treatments, medications, talk therapy,-- 22:47.000 --> 22:50.000 position:10%,start line:79.33% size:57.5% -- and shouldn't suffer depression because 22:50.000 --> 22:53.000 position:17.5%,start line:79.33% size:65% depression takes away your interpersonal relationships, 22:53.000 --> 22:58.000 position:27.5%,start line:79.33% size:42.5% your, your goals, your ability to move forward. 22:58.000 --> 22:59.000 position:30%,start line:79.33% size:37.5% It really takes everything. 22:59.000 --> 23:01.000 position:17.5%,start line:79.33% size:62.5% And it's really important that people get treatment. 23:01.000 --> 23:04.000 position:27.5%,start line:79.33% size:62.5% I want to shift gears for a couple of minutes and 23:04.000 --> 23:08.000 position:25%,start line:79.33% size:65% ask you about - as a young researcher a person who's 23:08.000 --> 23:11.000 position:25%,start line:79.33% size:47.5% focused on clinical care and also research, 23:11.000 --> 23:14.000 position:20%,start line:84.66% size:60% improving clinical care. 23:14.000 --> 23:18.000 position:22.5%,start line:79.33% size:55% What's it like for you to pursue a career in research? 23:18.000 --> 23:20.000 position:30%,start line:79.33% size:40% It can be really challenging. 23:20.000 --> 23:22.000 position:22.5%,start line:84.66% size:52.5% Thank you for asking. 23:22.000 --> 23:25.000 position:22.5%,start line:79.33% size:52.5% The thing that really keeps me going are the 23:25.000 --> 23:28.000 position:10%,start line:84.66% size:77.5% patients I take care of because 23:28.000 --> 23:31.000 position:12.5%,start line:79.33% size:75% depression is a horrible thing but people that suffer with it 23:31.000 --> 23:33.000 position:27.5%,start line:79.33% size:45% have an incredible understanding of what it 23:33.000 --> 23:36.000 position:17.5%,start line:79.33% size:65% means to be alive and what the challenges are of 23:36.000 --> 23:39.000 position:17.5%,start line:79.33% size:62.5% being here on this planet and it's, it's amazingly 23:39.000 --> 23:41.000 position:20%,start line:79.33% size:60% inspiring how they fight this illness 23:41.000 --> 23:42.000 position:20%,start line:84.66% size:60% and how they get better. 23:42.000 --> 23:46.000 position:27.5%,start line:79.33% size:45% So that part means I'm steadfast. 23:46.000 --> 23:49.000 position:20%,start line:79.33% size:60% But if it weren't for it - seriously if it weren't 23:49.000 --> 23:50.000 position:20%,start line:79.33% size:57.5% for private foundations like the 23:50.000 --> 23:51.000 position:27.5%,start line:79.33% size:45% Brain and Behavior Research Foundation, 23:51.000 --> 23:53.000 position:15%,start line:79.33% size:67.5% the American Foundation for Suicide Prevention, 23:53.000 --> 23:57.000 position:12.5%,start line:79.33% size:75% and private donors, I wouldn't be able to keep this going. 23:57.000 --> 23:59.000 position:20%,start line:79.33% size:57.5% And so there are days I am concerned about that. 23:59.000 --> 24:02.000 position:25%,start line:79.33% size:47.5% The amount of money that's dedicated toward 24:02.000 --> 24:05.000 position:22.5%,start line:79.33% size:55% depression and suicide prevention in this country 24:05.000 --> 24:06.000 position:32.5%,start line:79.33% size:35% in research is very minuscule. 24:06.000 --> 24:10.000 position:22.5%,start line:79.33% size:55% And I think we need to talk more about the fact 24:10.000 --> 24:13.000 position:17.5%,start line:79.33% size:62.5% that this is, this is the disease that causes the 24:13.000 --> 24:16.000 position:22.5%,start line:79.33% size:55% most disability and we need to address it. 24:16.000 --> 24:19.000 position:35%,start line:79.33% size:52.5% I think that's a very important issue that you 24:19.000 --> 24:22.000 position:25%,start line:79.33% size:65% bring up that lives can be changed by, one, 24:22.000 --> 24:26.000 position:15%,start line:79.33% size:75% making sure people have access to appropriate treatment and, 24:26.000 --> 24:29.000 position:20%,start line:79.33% size:60% two, making sure that we fund research so that new 24:29.000 --> 24:32.000 position:17.5%,start line:79.33% size:65% and even better treatments are available to people. 24:32.000 --> 24:34.000 position:27.5%,start line:79.33% size:45% And as you see one individual improve from 24:34.000 --> 24:37.000 position:20%,start line:79.33% size:57.5% this illness it affects everyone that they 24:37.000 --> 24:39.000 position:22.5%,start line:79.33% size:52.5% interact with, their, their children, 24:39.000 --> 24:41.000 position:22.5%,start line:79.33% size:52.5% their family members, the people they teach. 24:41.000 --> 24:42.000 position:27.5%,start line:84.66% size:45% So it really does. 24:42.000 --> 24:45.000 position:10%,start line:79.33% size:80% It's very rewarding to take care of people with this illness. 24:45.000 --> 24:48.000 position:20%,start line:79.33% size:60% Lisa I want to thank you so very much for joining 24:48.000 --> 24:51.000 position:27.5%,start line:79.33% size:42.5% us today and more importantly the work that 24:51.000 --> 24:54.000 position:25%,start line:79.33% size:47.5% you've done to help change the field, 24:54.000 --> 24:56.000 position:22.5%,start line:79.33% size:55% change people's lives, and the work that you're going 24:56.000 --> 24:58.000 position:17.5%,start line:84.66% size:62.5% to do in the years ahead. 24:58.000 --> 24:59.000 position:12.5%,start line:79.33% size:42.5% Thank you so much for having me here. 24:59.000 --> 25:00.000 position:65%,start line:84.66% size:25% Thank you. 25:03.000 --> 25:05.000 position:22.5%,start line:79.33% size:55% If you have depression don't suffer in silence. 25:05.000 --> 25:07.000 position:37.5%,start line:84.66% size:25% Seek help. 25:07.000 --> 25:11.000 position:10%,start line:79.33% size:77.5% And if your depression does not get better with treatment 25:11.000 --> 25:12.000 position:30%,start line:84.66% size:37.5% do not give up. 25:12.000 --> 25:17.000 position:15%,start line:79.33% size:67.5% Even people with refractory depression get better. 25:17.000 --> 25:18.000 position:22.5%,start line:79.33% size:55% As a result of cutting edge research 25:18.000 --> 25:22.000 position:10%,start line:84.66% size:77.5% with help, there truly is hope. 25:22.000 --> 25:25.000 position:30%,start line:79.33% size:40% Until next time, I'm Dr. Jeff Borenstein. 25:25.000 --> 25:27.000 position:40%,start line:84.66% size:20% Goodbye. 25:27.000 --> 25:36.000 position:47.5%,start line:84.66% size:5% ♪♪ 25:36.000 --> 25:37.000 position:30%,start line:79.33% size:40% (Dr. Borenstein) Do not suffer in silence. 25:37.000 --> 25:40.000 position:17.5%,start line:84.66% size:62.5% With help, there is hope. 25:40.000 --> 25:44.000 position:20%,start line:79.33% size:60% Healthy Minds is brought to you in part by: 25:44.000 --> 25:47.000 position:20%,start line:79.33% size:60% The American Psychiatric Association Foundation. 25:49.000 --> 25:53.000 position:27.5%,start line:79.33% size:42.5% The Graham Boeckh Foundation. 25:53.000 --> 25:57.000 position:22.5%,start line:79.33% size:55% And the New York State Office of Mental Health. 25:57.000 --> 26:04.000 position:47.5%,start line:10% size:5% ♪♪ 26:04.000 --> 26:07.000 position:17.5%,start line:10% size:65% If you would like to watch our expert interview in 26:07.000 --> 26:12.000 position:17.5%,start line:10% size:62.5% its entirety log onto bbr foundation dot org slash 26:12.000 --> 26:13.000 position:32.5%,start line:10% size:35% Healthy Minds. 26:13.000 --> 26:44.000 position:47.5%,start line:10% size:5% ♪♪