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Welcome to Healthy Minds,

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I'm Dr. Jeff Borenstein.

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Everyone is touched by

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psychiatric conditions,

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either themselves

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or a loved one.

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Do not suffer in silence.

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With help, there is hope.

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Today on Health Minds:

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(Dr. Lisa Pan)

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We had tried literally

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every medication available.

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We had even done

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experimental medications and

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nothing happened.

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And in fact, at the time that we

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made this discovery,

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he was in an

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inpatient psychiatric facility,

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horribly depressed,

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on 17 medications

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just to try to keep

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him safe.

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And he was not having a

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response nor was he really

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having side effects so I had not

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ever seen anything like that.

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And so we repurposed this

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molecule and gave it to him

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and we started

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to see improvement.

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And we saw some

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fascinating changes.

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He is now four years healthy,

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I'm sorry, five years healthy

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and with no psychiatric

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medication just with this

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replacement molecule.

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(Dr. Borenstein)

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That's today on Healthy Minds.

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Healthy Minds is brought

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to you in part by:

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The American Psychiatric

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Association Foundation.

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The Graham Boeckh

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Foundation.

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And the New York State

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Office of Mental Health.

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Welcome to Healthy Minds,

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I'm Dr. Jeff Borenstein.

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Depression is extremely

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common and for those who

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experience this illness,

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extremely painful.

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Fortunately, most people

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with depression who seek help

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respond to treatment,

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but some people do not.

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Today I speak with leading

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researcher Dr. Lisa Pan

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about refractory

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depression and new approaches

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to helping

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people who do not get

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better with the usual

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medicines and therapy.

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Lisa welcome.

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Thank you.

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Thank you for

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joining us today.

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Thank you so much

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for having me here.

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I appreciate it.

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Your work has focused

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on depression and in

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particular what we call

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refractory depression.

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I'd like you to define

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what refractory depression is.

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So I think the most

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important thing to know is

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that depression isn't

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just regular sadness.

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So somebody who's never

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had depression,

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probably can't understand the

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severity of the low mood.

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And we look for symptoms

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in depression that include

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this, this deep sadness or

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- some people describe

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even emotionless or like

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it sad, a sadness that's

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almost destructive.

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And then also low energy levels,

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not being able to

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enjoy anything

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that you used to.

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And I mean like we call

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it anhedonia and it's an

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inability to enjoy other people,

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activities that you love,

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even basic things.

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And then we also see guilt,

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inappropriate guilt,

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about things that really aren't

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the person's fault.

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Hopelessness

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about the future.

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So people with a very

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severe depression will

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think that everything in

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the past was worthless.

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What's going on now is

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worthless and there's no

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hope for anything of

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value in the future.

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Also we'll see things like

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low self-esteem and then

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what can be really life

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threatening is thoughts

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about death and thoughts

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about suicide which can be

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pervasive because the

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depression is so severe.

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And the frequency of depression,

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what are the statistics

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about that because it's a

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very common illness.

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And so it's estimated that

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5% of the population at

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any given time

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has depression.

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25% of the population will have

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it at some time in their life.

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The population that we

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have been most interested in

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are treatment refractory and

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about 15% of patients

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won't respond to available

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treatments for depression.

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Treatment refractory

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depression affects about,

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estimates are 15%

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of people that have

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depression and that is

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defined in a variety of ways.

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We define that as having

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three full dose,

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full duration medication

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treatments

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that there was no response.

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So people came for

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treatment were given

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appropriate medication at

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a full dose for a

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full period of time that one

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would expect them to respond.

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Right.

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And they didn't

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respond.

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And that happened

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three times.

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Right.

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And the majority of the

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people in our study

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honestly have had far more

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than three treatments.

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I think what has been the

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most concerning for me is

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how this is really life

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threatening and that,

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you know, we, we have a couple

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issues that interfere in

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the ability to

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treat depression.

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One is stigma so that

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people don't come forward

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to get treatment.

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The second is a lack of

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understanding of the fact

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that this is a medical

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condition and requires

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medical treatment.

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And then I think the third

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thing is that because the

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people are hopeless you,

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there's really not a lot

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of motivation

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to get better.

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You really need an

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advocate and a treatment

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team that's going to push

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you forward and make sure

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that you're getting

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what you need.

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And so this is an illness

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that by its very nature

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makes it harder

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to treat it.

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What we do now for

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treatment refractory

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depression are things like

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ketamine treatment,

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vagus nerve stimulators,

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electroconvulsive therapy

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is our most effective

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treatment for depression

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and many of the patients

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in the study have had these.

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So people have not only

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not responded to the usual

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treatments they've had

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some treatments such as

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electroconvulsive

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treatment, some more

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experimental treatments

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such as ketamine which is

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a rapid acting

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anti-depressant and

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haven't responded even

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to those treatments.

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And then--

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And then--

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-- what happens?

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-- come to me.

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Ok

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And the reason why I think

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that we're studying that

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population that's had such

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severe illness and has not

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responded is that the

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disorders we're finding

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are related to an

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inability to either

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metabolize important

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molecules and chemicals in

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the body or an inability to

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generate neurotransmitters.

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So we have a lot of

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effective treatments for

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moderate depression or

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even severe depression

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that's not treatment

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refractory.

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But what I think is

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happening and this is, you know,

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based on the little

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bit of work I've done so far,

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is that if you're not generating

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neurotransmitters,

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blocking the reuptake to

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increase their levels is not

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going to be effective and that

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may be part of the reason

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we're seeing patients

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that aren't

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responding to multiple

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medication trials.

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So one of our forms of

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treatment is to try to

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increase a certain

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neurochemical or

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neurochemicals by blocking

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how much it's taken back

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up into the neuron

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that sends it out.

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Exactly.

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But if we're not, if we're

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not producing enough of

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that due to some metabolic

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kind of issue then that

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form of treatment may not

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be why it's not effective

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for those people.

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And that's what we're finding in

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this patient population

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is we're

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working backwards from the

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end metabolite in a biochemical

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pathway and trying to

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determine based on what's

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missing what needs to be

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replaced.

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And so that's the core of

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what we're doing with this

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metabolomic study is, is

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working backwards to see

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if there are metabolic

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pathways that are affected

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either from primary causes

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or secondary causes.

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So a primary cause would be an

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inheritable inborn metabolism,

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a secondary cause might be

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some environmental insult

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that we're not aware of

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but by replacing what's

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missing we're seeing

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some improvement.

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Now how do you determine

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that somebody is missing

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one of these metabolites.

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So this study we do right

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now does a very broad

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based approach to

307
00:07:16,000 --> 00:07:18,000
metabolic disease where we

308
00:07:18,000 --> 00:07:21,000
look at blood, urine, and

309
00:07:18,000 --> 00:07:21,000
the most important thing

310
00:07:21,000 --> 00:07:22,000
is cerebrospinal fluid.

311
00:07:22,000 --> 00:07:24,000
So we actually do a lumbar

312
00:07:22,000 --> 00:07:24,000
puncture to collect

313
00:07:24,000 --> 00:07:27,000
cerebrospinal fluid from

314
00:07:24,000 --> 00:07:27,000
the central nervous system

315
00:07:27,000 --> 00:07:32,000
and look at chemicals

316
00:07:27,000 --> 00:07:32,000
in that CSF sample.

317
00:07:32,000 --> 00:07:35,000
We look at

318
00:07:32,000 --> 00:07:35,000
neurotransmitter metabolites,

319
00:07:35,000 --> 00:07:37,000
markers of

320
00:07:35,000 --> 00:07:37,000
vitamin metabolism and a

321
00:07:37,000 --> 00:07:40,000
small molecule called

322
00:07:37,000 --> 00:07:40,000
tetrahydrobiopterin which

323
00:07:40,000 --> 00:07:42,000
is crucial to make

324
00:07:40,000 --> 00:07:42,000
neurotransmitters,

325
00:07:42,000 --> 00:07:46,000
pain modulators, and melatonin

326
00:07:42,000 --> 00:07:46,000
which regulates sleep.

327
00:07:46,000 --> 00:07:49,000
And so if that's missing

328
00:07:46,000 --> 00:07:49,000
it affects all those pathways.

329
00:07:49,000 --> 00:07:53,000
So what types of findings

330
00:07:49,000 --> 00:07:53,000
have you had in this,

331
00:07:53,000 --> 00:07:55,000
in this research and

332
00:07:53,000 --> 00:07:55,000
clinical work?

333
00:07:55,000 --> 00:07:57,000
So if it's ok I'll talk a

334
00:07:55,000 --> 00:07:57,000
little bit about the first

335
00:07:57,000 --> 00:07:58,000
patient who--

336
00:07:58,000 --> 00:08:00,000
--Perfect.

337
00:08:00,000 --> 00:08:02,000
So that just to explain why

338
00:08:00,000 --> 00:08:02,000
we started doing this.

339
00:08:02,000 --> 00:08:05,000
So I had a young man and I,

340
00:08:02,000 --> 00:08:05,000
he's given permission

341
00:08:05,000 --> 00:08:08,000
to discuss his care and

342
00:08:05,000 --> 00:08:08,000
we actually published his

343
00:08:08,000 --> 00:08:12,000
case so that he, other

344
00:08:08,000 --> 00:08:12,000
people could be helped.

345
00:08:12,000 --> 00:08:16,000
So he came to us as a

346
00:08:12,000 --> 00:08:16,000
tertiary referral because

347
00:08:16,000 --> 00:08:18,000
of significant suicidal

348
00:08:16,000 --> 00:08:18,000
behavior and depression

349
00:08:18,000 --> 00:08:20,000
that was not responding

350
00:08:18,000 --> 00:08:20,000
to treatment.

351
00:08:20,000 --> 00:08:23,000
And what had happened

352
00:08:20,000 --> 00:08:23,000
is that we had tried

353
00:08:23,000 --> 00:08:26,000
literally every medication

354
00:08:23,000 --> 00:08:26,000
available, we'd even done

355
00:08:26,000 --> 00:08:29,000
experimental medications

356
00:08:26,000 --> 00:08:29,000
like you talked about

357
00:08:29,000 --> 00:08:32,000
including a medicine for

358
00:08:29,000 --> 00:08:32,000
Lou Gehrig's disease

359
00:08:32,000 --> 00:08:34,000
that's shown some promise

360
00:08:32,000 --> 00:08:34,000
in anxiety and depression

361
00:08:34,000 --> 00:08:35,000
and nothing happened.

362
00:08:35,000 --> 00:08:38,000
And in fact at the

363
00:08:35,000 --> 00:08:38,000
time that we made this discovery

364
00:08:38,000 --> 00:08:41,000
he was in an

365
00:08:38,000 --> 00:08:41,000
inpatient psychiatric facility,

366
00:08:41,000 --> 00:08:44,000
horribly depressed,

367
00:08:41,000 --> 00:08:44,000
on 17 medications

368
00:08:44,000 --> 00:08:47,000
just to try to

369
00:08:44,000 --> 00:08:47,000
keep him safe and he was

370
00:08:47,000 --> 00:08:49,000
not having a response nor was he

371
00:08:47,000 --> 00:08:49,000
really having side effects

372
00:08:49,000 --> 00:08:51,000
so I had never

373
00:08:49,000 --> 00:08:51,000
seen anything like that.

374
00:08:51,000 --> 00:08:53,000
It was like we weren't

375
00:08:51,000 --> 00:08:53,000
doing anything.

376
00:08:53,000 --> 00:08:56,000
He was trying to end

377
00:08:53,000 --> 00:08:56,000
his life on the unit.

378
00:08:56,000 --> 00:09:00,000
And so I went to a

379
00:08:56,000 --> 00:09:00,000
biochemical geneticist who

380
00:09:00,000 --> 00:09:04,000
had trained me named

381
00:09:00,000 --> 00:09:04,000
David Finegold and I said

382
00:09:04,000 --> 00:09:06,000
there was a study in the 1980s

383
00:09:04,000 --> 00:09:06,000
that National Institutes

384
00:09:06,000 --> 00:09:09,000
of Health showing that

385
00:09:06,000 --> 00:09:09,000
patients who had severe

386
00:09:09,000 --> 00:09:12,000
near lethal suicide

387
00:09:09,000 --> 00:09:12,000
attempts had low

388
00:09:12,000 --> 00:09:16,000
5-hydroxyindoleacetic acid

389
00:09:12,000 --> 00:09:16,000
in their central nervous system,

390
00:09:16,000 --> 00:09:19,000
in the CSF samples,

391
00:09:16,000 --> 00:09:19,000
cerebrospinal fluid.

392
00:09:19,000 --> 00:09:22,000
And I asked him "Is there

393
00:09:19,000 --> 00:09:22,000
any way you can tell me

394
00:09:22,000 --> 00:09:24,000
"anything about his

395
00:09:22,000 --> 00:09:24,000
neurotransmitter profile

396
00:09:24,000 --> 00:09:26,000
so I have some idea of

397
00:09:24,000 --> 00:09:26,000
what's going on here."

398
00:09:26,000 --> 00:09:28,000
And he said to me

399
00:09:26,000 --> 00:09:28,000
"I can do better than that.

400
00:09:28,000 --> 00:09:30,000
"We can run the whole

401
00:09:28,000 --> 00:09:30,000
neurologic panel that we do

402
00:09:30,000 --> 00:09:34,000
"for seizure, and you

403
00:09:30,000 --> 00:09:34,000
know neurodegenerative disease",

404
00:09:34,000 --> 00:09:36,000
and when he did

405
00:09:34,000 --> 00:09:36,000
that he found this missing

406
00:09:36,000 --> 00:09:38,000
small molecule

407
00:09:36,000 --> 00:09:38,000
tetrahydrobiopterin

408
00:09:38,000 --> 00:09:40,000
it's also called BH4.

409
00:09:40,000 --> 00:09:42,000
It was low.

410
00:09:42,000 --> 00:09:46,000
So the range starts at 10

411
00:09:42,000 --> 00:09:46,000
and his was at 9 which

412
00:09:46,000 --> 00:09:49,000
doesn't sound ridiculous

413
00:09:46,000 --> 00:09:49,000
but it's a big difference

414
00:09:49,000 --> 00:09:52,000
because a young healthy

415
00:09:49,000 --> 00:09:52,000
person should be in the

416
00:09:52,000 --> 00:09:54,000
middle to the top

417
00:09:52,000 --> 00:09:54,000
end of that range.

418
00:09:54,000 --> 00:09:58,000
And what was fascinating

419
00:09:54,000 --> 00:09:58,000
is that they make this molecule

420
00:09:58,000 --> 00:10:02,000
to treat another disease called

421
00:09:58,000 --> 00:10:02,000
phenylketonuria.

422
00:10:02,000 --> 00:10:04,000
And so we repurposed this

423
00:10:02,000 --> 00:10:04,000
molecule and gave it to

424
00:10:04,000 --> 00:10:07,000
him and we started

425
00:10:04,000 --> 00:10:07,000
seeing improvement.

426
00:10:07,000 --> 00:10:09,000
And we saw some

427
00:10:07,000 --> 00:10:09,000
fascinating changes which made

428
00:10:09,000 --> 00:10:12,000
me really feel like we had to

429
00:10:09,000 --> 00:10:12,000
keep looking for other people.

430
00:10:12,000 --> 00:10:16,000
In the first eight weeks

431
00:10:12,000 --> 00:10:16,000
he landscaped his mother's yard.

432
00:10:16,000 --> 00:10:19,000
He was having

433
00:10:16,000 --> 00:10:19,000
inappropriate feelings of

434
00:10:19,000 --> 00:10:21,000
love towards people

435
00:10:19,000 --> 00:10:21,000
on the phone.

436
00:10:21,000 --> 00:10:25,000
Very bizarre changes that

437
00:10:21,000 --> 00:10:25,000
he was describing as bizarre.

438
00:10:25,000 --> 00:10:29,000
And so I knew something

439
00:10:25,000 --> 00:10:29,000
was happening and what was

440
00:10:29,000 --> 00:10:31,000
fascinating is that as

441
00:10:29,000 --> 00:10:31,000
this progressed he's now

442
00:10:31,000 --> 00:10:36,000
four years healthy, I'm

443
00:10:31,000 --> 00:10:36,000
sorry five years healthy,

444
00:10:36,000 --> 00:10:39,000
and with no psychiatric

445
00:10:36,000 --> 00:10:39,000
medication just with this

446
00:10:39,000 --> 00:10:40,000
replacement molecule.

447
00:10:40,000 --> 00:10:44,000
And so when I saw that my,

448
00:10:40,000 --> 00:10:44,000
my whole career changed.

449
00:10:44,000 --> 00:10:47,000
So I work in a clinic

450
00:10:44,000 --> 00:10:47,000
started by Dr. David Brent

451
00:10:47,000 --> 00:10:50,000
that is a-- it's services

452
00:10:47,000 --> 00:10:50,000
for teens at risk.

453
00:10:50,000 --> 00:10:53,000
And that we specialize in

454
00:10:50,000 --> 00:10:53,000
suicide prevention

455
00:10:53,000 --> 00:10:54,000
and depression.

456
00:10:54,000 --> 00:10:56,000
And so I started looking

457
00:10:54,000 --> 00:10:56,000
at the patients I had that

458
00:10:56,000 --> 00:10:58,000
were not improving.

459
00:10:58,000 --> 00:10:59,000
And the next three

460
00:10:58,000 --> 00:10:59,000
patients we tested also

461
00:10:59,000 --> 00:11:01,000
had a metabolic disorder.

462
00:11:01,000 --> 00:11:04,000
And those three patients had a

463
00:11:01,000 --> 00:11:04,000
disorder of folate metabolism

464
00:11:04,000 --> 00:11:06,000
so that they're

465
00:11:04,000 --> 00:11:06,000
folate looks totally

466
00:11:06,000 --> 00:11:08,000
normal in their blood,

467
00:11:06,000 --> 00:11:08,000
but when we test the central

468
00:11:08,000 --> 00:11:11,000
nervous system, the

469
00:11:08,000 --> 00:11:11,000
folate's not either

470
00:11:11,000 --> 00:11:12,000
crossing in the central

471
00:11:11,000 --> 00:11:12,000
nervous system or being

472
00:11:12,000 --> 00:11:15,000
processed appropriately so it's

473
00:11:12,000 --> 00:11:15,000
available to the neurons,

474
00:11:15,000 --> 00:11:18,000
and so that too affects

475
00:11:15,000 --> 00:11:18,000
neurotransmitter metabolism.

476
00:11:18,000 --> 00:11:22,000
We expected to maybe find 10% of

477
00:11:18,000 --> 00:11:22,000
patients had something,

478
00:11:22,000 --> 00:11:24,000
we had no idea

479
00:11:22,000 --> 00:11:24,000
we were going to find that

480
00:11:24,000 --> 00:11:26,000
two thirds of the patients

481
00:11:24,000 --> 00:11:26,000
we tested had something

482
00:11:26,000 --> 00:11:27,000
and that there would be

483
00:11:26,000 --> 00:11:27,000
treatments available.

484
00:11:27,000 --> 00:11:30,000
So of the people that you

485
00:11:27,000 --> 00:11:30,000
were looking at who were

486
00:11:30,000 --> 00:11:33,000
these people who have

487
00:11:30,000 --> 00:11:33,000
refractory depression not

488
00:11:33,000 --> 00:11:36,000
responding to the usual

489
00:11:33,000 --> 00:11:36,000
treatments and maybe other

490
00:11:36,000 --> 00:11:40,000
treatments, two thirds

491
00:11:36,000 --> 00:11:40,000
had, you were able to find,

492
00:11:40,000 --> 00:11:43,000
had some metabolic

493
00:11:40,000 --> 00:11:43,000
issue that could be corrected.

494
00:11:43,000 --> 00:11:45,000
Yes.

495
00:11:45,000 --> 00:11:47,000
And we're just now, as the

496
00:11:45,000 --> 00:11:47,000
study is expanding,

497
00:11:47,000 --> 00:11:49,000
we're just now starting to

498
00:11:47,000 --> 00:11:49,000
bring people back.

499
00:11:49,000 --> 00:11:52,000
We refer out to

500
00:11:49,000 --> 00:11:52,000
geneticists to treat and

501
00:11:52,000 --> 00:11:54,000
then we bring them back to

502
00:11:52,000 --> 00:11:54,000
follow up so I'm hoping

503
00:11:54,000 --> 00:11:57,000
we'll have more data about

504
00:11:54,000 --> 00:11:57,000
how many people have responded

505
00:11:57,000 --> 00:11:59,000
but so far we've

506
00:11:57,000 --> 00:11:59,000
had some improvement in

507
00:11:59,000 --> 00:12:00,000
everyone that

508
00:11:59,000 --> 00:12:00,000
we've followed up.

509
00:12:00,000 --> 00:12:04,000
Could you tell us a little

510
00:12:00,000 --> 00:12:04,000
bit more about some of the

511
00:12:04,000 --> 00:12:07,000
metabolic deficiencies and

512
00:12:04,000 --> 00:12:07,000
changes that you've

513
00:12:07,000 --> 00:12:08,000
seen in people.

514
00:12:08,000 --> 00:12:11,000
So the first one that we

515
00:12:08,000 --> 00:12:11,000
found is a disorder of

516
00:12:11,000 --> 00:12:14,000
tetrahydrobiopterin and

517
00:12:11,000 --> 00:12:14,000
there are a couple of

518
00:12:14,000 --> 00:12:16,000
different ways you can

519
00:12:14,000 --> 00:12:16,000
get a tetrahydrobiopterin

520
00:12:16,000 --> 00:12:19,000
deficiency but they're

521
00:12:16,000 --> 00:12:19,000
all treated the same.

522
00:12:19,000 --> 00:12:22,000
And that is, that is a

523
00:12:19,000 --> 00:12:22,000
small molecule in the

524
00:12:22,000 --> 00:12:23,000
central nervous system.

525
00:12:23,000 --> 00:12:25,000
We find a

526
00:12:23,000 --> 00:12:25,000
deficiency from the

527
00:12:25,000 --> 00:12:27,000
cerebrospinal fluid testing

528
00:12:25,000 --> 00:12:27,000
that we do.

529
00:12:27,000 --> 00:12:30,000
And then there's a

530
00:12:27,000 --> 00:12:30,000
replacement therapy for that.

531
00:12:30,000 --> 00:12:31,000
I think the reason that

532
00:12:30,000 --> 00:12:31,000
one has been one of the

533
00:12:31,000 --> 00:12:36,000
most severe presentations

534
00:12:31,000 --> 00:12:36,000
in phenotype is that it's

535
00:12:36,000 --> 00:12:40,000
required, that molecules

536
00:12:36,000 --> 00:12:40,000
required to make serotonin,

537
00:12:40,000 --> 00:12:45,000
dopamine, pain modulators,

538
00:12:40,000 --> 00:12:45,000
and also melatonin

539
00:12:45,000 --> 00:12:49,000
it helps regulate the

540
00:12:45,000 --> 00:12:49,000
body's function.

541
00:12:49,000 --> 00:12:52,000
Furthermore it can affect white

542
00:12:49,000 --> 00:12:52,000
matter and neuronal structure.

543
00:12:52,000 --> 00:12:56,000
So that that can have a drastic

544
00:12:52,000 --> 00:12:56,000
effect on brain function.

545
00:12:56,000 --> 00:12:58,000
So not having it not

546
00:12:56,000 --> 00:12:58,000
really affects the brain

547
00:12:58,000 --> 00:13:00,000
in a multitude

548
00:12:58,000 --> 00:13:00,000
of ways.

549
00:13:00,000 --> 00:13:01,000
Yes.

550
00:13:01,000 --> 00:13:02,000
The second disorder which

551
00:13:01,000 --> 00:13:02,000
is the most common one we

552
00:13:02,000 --> 00:13:05,000
found is called cerebral

553
00:13:02,000 --> 00:13:05,000
folate deficiency.

554
00:13:05,000 --> 00:13:08,000
That's defined as having

555
00:13:05,000 --> 00:13:08,000
normal circulating folate

556
00:13:08,000 --> 00:13:11,000
in the blood but deficient

557
00:13:08,000 --> 00:13:11,000
folate in the central

558
00:13:11,000 --> 00:13:13,000
nervous system and again

559
00:13:11,000 --> 00:13:13,000
we find that through

560
00:13:13,000 --> 00:13:15,000
cerebrospinal fluid

561
00:13:13,000 --> 00:13:15,000
testing.

562
00:13:15,000 --> 00:13:18,000
Again this is very crucial

563
00:13:15,000 --> 00:13:18,000
to neurotransmitter metabolism.

564
00:13:18,000 --> 00:13:21,000
The folate pathway

565
00:13:18,000 --> 00:13:21,000
directly interacts with

566
00:13:21,000 --> 00:13:24,000
amino acid metabolism

567
00:13:21,000 --> 00:13:24,000
and the generation of

568
00:13:24,000 --> 00:13:27,000
serotonin and dopamine,

569
00:13:24,000 --> 00:13:27,000
and so there's a clear

570
00:13:27,000 --> 00:13:29,000
biochemical reason

571
00:13:27,000 --> 00:13:29,000
for depression.

572
00:13:29,000 --> 00:13:31,000
And again in the

573
00:13:29,000 --> 00:13:31,000
neurologic forms of

574
00:13:31,000 --> 00:13:33,000
cerebral folate

575
00:13:31,000 --> 00:13:33,000
deficiency, we actually

576
00:13:33,000 --> 00:13:35,000
see visible white matter

577
00:13:33,000 --> 00:13:35,000
changes on MRI.

578
00:13:35,000 --> 00:13:37,000
So we know there's a

579
00:13:35,000 --> 00:13:37,000
structural component to

580
00:13:37,000 --> 00:13:40,000
not having folate present

581
00:13:37,000 --> 00:13:40,000
the central nervous system

582
00:13:40,000 --> 00:13:43,000
that can affect white

583
00:13:40,000 --> 00:13:43,000
matter, the myelin that

584
00:13:43,000 --> 00:13:46,000
covers the brain and

585
00:13:43,000 --> 00:13:46,000
protects the brain and

586
00:13:46,000 --> 00:13:49,000
allows for communication,

587
00:13:46,000 --> 00:13:49,000
and also the neuron itself

588
00:13:49,000 --> 00:13:51,000
the axons of the neuron

589
00:13:49,000 --> 00:13:51,000
can be affected by

590
00:13:51,000 --> 00:13:53,000
having deficient folate.

591
00:13:53,000 --> 00:13:55,000
And with deficient folate

592
00:13:53,000 --> 00:13:55,000
there's also an ability to

593
00:13:55,000 --> 00:13:58,000
give medicine that

594
00:13:55,000 --> 00:13:58,000
can remediate that.

595
00:13:58,000 --> 00:14:00,000
Exactly so we give a form

596
00:13:58,000 --> 00:14:00,000
of folate that the body

597
00:14:00,000 --> 00:14:03,000
doesn't have to act

598
00:14:00,000 --> 00:14:03,000
on for it to function.

599
00:14:03,000 --> 00:14:05,000
There's two forms.

600
00:14:05,000 --> 00:14:07,000
Depending on what the

601
00:14:05,000 --> 00:14:07,000
disorder is,

602
00:14:07,000 --> 00:14:09,000
different forms are needed.

603
00:14:09,000 --> 00:14:11,000
What's amazing though is

604
00:14:09,000 --> 00:14:11,000
we know from neurologic

605
00:14:11,000 --> 00:14:13,000
studies from quite some

606
00:14:11,000 --> 00:14:13,000
time ago that when you

607
00:14:13,000 --> 00:14:17,000
give the folate, the white

608
00:14:13,000 --> 00:14:17,000
matter change is correct.

609
00:14:17,000 --> 00:14:20,000
So it's an important thing

610
00:14:17,000 --> 00:14:20,000
for the brain to have.

611
00:14:20,000 --> 00:14:22,000
And so that's the

612
00:14:20,000 --> 00:14:22,000
second thing we found.

613
00:14:22,000 --> 00:14:27,000
The third is a disorder,

614
00:14:22,000 --> 00:14:27,000
on a profile, a blood profile

615
00:14:27,000 --> 00:14:29,000
called

616
00:14:27,000 --> 00:14:29,000
acylcarnitine profiling.

617
00:14:29,000 --> 00:14:33,000
And this is, it's a hint

618
00:14:29,000 --> 00:14:33,000
that there's a disorder of

619
00:14:33,000 --> 00:14:35,000
energy metabolism.

620
00:14:35,000 --> 00:14:36,000
But we have to

621
00:14:35,000 --> 00:14:36,000
find out why.

622
00:14:36,000 --> 00:14:39,000
And so we refer to medical

623
00:14:36,000 --> 00:14:39,000
genetics to do further

624
00:14:39,000 --> 00:14:42,000
testing but some of those

625
00:14:39,000 --> 00:14:42,000
disorders can be treated

626
00:14:42,000 --> 00:14:46,000
with riboflavin and the

627
00:14:42,000 --> 00:14:46,000
person will improve.

628
00:14:46,000 --> 00:14:49,000
In the people who you've seen

629
00:14:46,000 --> 00:14:49,000
who've had these deficiencies,

630
00:14:49,000 --> 00:14:53,000
did the, was

631
00:14:49,000 --> 00:14:53,000
the depression occurring

632
00:14:53,000 --> 00:14:55,000
throughout their life or

633
00:14:53,000 --> 00:14:55,000
just started at a certain

634
00:14:55,000 --> 00:14:57,000
point in time and how

635
00:14:55,000 --> 00:14:57,000
does that relate to this

636
00:14:57,000 --> 00:14:59,000
deficiency issue?

637
00:14:59,000 --> 00:15:03,000
This is a fascinating

638
00:14:59,000 --> 00:15:03,000
question so I'll say first

639
00:15:03,000 --> 00:15:06,000
we have a full range in

640
00:15:03,000 --> 00:15:06,000
this but almost everyone

641
00:15:06,000 --> 00:15:08,000
it was early childhood

642
00:15:06,000 --> 00:15:08,000
or at puberty.

643
00:15:08,000 --> 00:15:12,000
And this is important

644
00:15:08,000 --> 00:15:12,000
because in, in biochemical

645
00:15:12,000 --> 00:15:14,000
genetics there are many

646
00:15:12,000 --> 00:15:14,000
disorders that have an

647
00:15:14,000 --> 00:15:17,000
onset at puberty or at

648
00:15:14,000 --> 00:15:17,000
a time of stress to the body.

649
00:15:17,000 --> 00:15:21,000
So disorders that will

650
00:15:17,000 --> 00:15:21,000
come on after pregnancy or

651
00:15:21,000 --> 00:15:23,000
disorders that will come

652
00:15:21,000 --> 00:15:23,000
on at puberty because of

653
00:15:23,000 --> 00:15:24,000
hormonal changes.

654
00:15:24,000 --> 00:15:26,000
And that's true in

655
00:15:24,000 --> 00:15:26,000
psychiatry also.

656
00:15:26,000 --> 00:15:28,000
And so I have wondered

657
00:15:26,000 --> 00:15:28,000
about the relationship

658
00:15:28,000 --> 00:15:31,000
between onset and the

659
00:15:28,000 --> 00:15:31,000
fact that these might be

660
00:15:31,000 --> 00:15:33,000
metabolic conditions that

661
00:15:31,000 --> 00:15:33,000
are contributing to the

662
00:15:33,000 --> 00:15:34,000
psychiatric phenotype.

663
00:15:34,000 --> 00:15:39,000
So it might be that, that

664
00:15:34,000 --> 00:15:39,000
sort of a storyline of

665
00:15:39,000 --> 00:15:43,000
these refractory

666
00:15:39,000 --> 00:15:43,000
depression people who have

667
00:15:43,000 --> 00:15:47,000
had who haven't responded

668
00:15:43,000 --> 00:15:47,000
to anything but may,

669
00:15:47,000 --> 00:15:50,000
may have a metabolic issue and

670
00:15:47,000 --> 00:15:50,000
may respond to that,

671
00:15:50,000 --> 00:15:52,000
these are people who the

672
00:15:50,000 --> 00:15:52,000
depression might have

673
00:15:52,000 --> 00:15:55,000
started in childhood

674
00:15:52,000 --> 00:15:55,000
and that might be an

675
00:15:55,000 --> 00:15:59,000
indication that they're

676
00:15:55,000 --> 00:15:59,000
at greater risk of being

677
00:15:59,000 --> 00:16:00,000
found to have this.

678
00:16:00,000 --> 00:16:03,000
Yeah, I think we have a

679
00:16:00,000 --> 00:16:03,000
small  N  but that's been

680
00:16:03,000 --> 00:16:05,000
true in the population

681
00:16:03,000 --> 00:16:05,000
we studied so far.

682
00:16:05,000 --> 00:16:08,000
For somebody who's

683
00:16:05,000 --> 00:16:08,000
watching at home right now,

684
00:16:08,000 --> 00:16:10,000
who either they

685
00:16:08,000 --> 00:16:10,000
themselves have a

686
00:16:10,000 --> 00:16:13,000
depression that hasn't

687
00:16:10,000 --> 00:16:13,000
respond to treatment or a

688
00:16:13,000 --> 00:16:17,000
loved one, family member

689
00:16:13,000 --> 00:16:17,000
has that, what should they do?

690
00:16:17,000 --> 00:16:19,000
I think it's really

691
00:16:17,000 --> 00:16:19,000
important for me to say

692
00:16:19,000 --> 00:16:20,000
that this is very

693
00:16:19,000 --> 00:16:20,000
preliminary.

694
00:16:20,000 --> 00:16:23,000
I think, I think it's

695
00:16:20,000 --> 00:16:23,000
exciting and it gives us

696
00:16:23,000 --> 00:16:25,000
an idea that there may be

697
00:16:23,000 --> 00:16:25,000
things happening we didn't

698
00:16:25,000 --> 00:16:27,000
know about before.

699
00:16:27,000 --> 00:16:29,000
But right now what we're

700
00:16:27,000 --> 00:16:29,000
desperately trying to do

701
00:16:29,000 --> 00:16:32,000
is find a way to test the

702
00:16:29,000 --> 00:16:32,000
blood so that this will be

703
00:16:32,000 --> 00:16:34,000
available to everyone.

704
00:16:34,000 --> 00:16:38,000
But it's so, it's in

705
00:16:34,000 --> 00:16:38,000
preliminary stages.

706
00:16:38,000 --> 00:16:42,000
We don't know really how,

707
00:16:38,000 --> 00:16:42,000
how well people will

708
00:16:42,000 --> 00:16:44,000
respond or if people that

709
00:16:42,000 --> 00:16:44,000
are less severe are going

710
00:16:44,000 --> 00:16:46,000
to have similar disorders.

711
00:16:46,000 --> 00:16:50,000
But I would say that I'd

712
00:16:46,000 --> 00:16:50,000
have hope because I think

713
00:16:50,000 --> 00:16:52,000
the field is

714
00:16:50,000 --> 00:16:52,000
expanding quickly.

715
00:16:52,000 --> 00:16:54,000
We're finding new things

716
00:16:52,000 --> 00:16:54,000
that maybe contributing to

717
00:16:54,000 --> 00:16:59,000
depression and so I do

718
00:16:54,000 --> 00:16:59,000
think there's going to be

719
00:16:59,000 --> 00:17:01,000
potentially alternative

720
00:16:59,000 --> 00:17:01,000
treatments available in

721
00:17:01,000 --> 00:17:03,000
the future.

722
00:17:03,000 --> 00:17:05,000
Should people who are

723
00:17:03,000 --> 00:17:05,000
experiencing

724
00:17:05,000 --> 00:17:10,000
refractory depression, sort of

725
00:17:05,000 --> 00:17:10,000
go for additional treatment,

726
00:17:10,000 --> 00:17:12,000
maybe more specialized

727
00:17:10,000 --> 00:17:12,000
treatment, maybe in an

728
00:17:12,000 --> 00:17:17,000
academic setting where

729
00:17:12,000 --> 00:17:17,000
perhaps they can be

730
00:17:17,000 --> 00:17:20,000
checked for some of

731
00:17:17,000 --> 00:17:20,000
these metabolite issues?

732
00:17:20,000 --> 00:17:22,000
I do think if you have a

733
00:17:20,000 --> 00:17:22,000
family member or if you

734
00:17:22,000 --> 00:17:24,000
yourself are, have not

735
00:17:22,000 --> 00:17:24,000
responded to what's

736
00:17:24,000 --> 00:17:26,000
available it makes sense

737
00:17:24,000 --> 00:17:26,000
to see what else you can

738
00:17:26,000 --> 00:17:28,000
find for sure.

739
00:17:28,000 --> 00:17:31,000
Where do you see the

740
00:17:28,000 --> 00:17:31,000
research moving as we look

741
00:17:31,000 --> 00:17:34,000
over the next few years

742
00:17:31,000 --> 00:17:34,000
for treating depression

743
00:17:34,000 --> 00:17:37,000
and in particular

744
00:17:34,000 --> 00:17:37,000
refractory depression?

745
00:17:37,000 --> 00:17:41,000
I'm hoping that there will

746
00:17:37,000 --> 00:17:41,000
be other academic centers

747
00:17:41,000 --> 00:17:43,000
that will replicate what

748
00:17:41,000 --> 00:17:43,000
we've found and if we find

749
00:17:43,000 --> 00:17:48,000
this is legitimately being

750
00:17:43,000 --> 00:17:48,000
present in this population

751
00:17:48,000 --> 00:17:50,000
that we'll find a way

752
00:17:48,000 --> 00:17:50,000
to streamline medical

753
00:17:50,000 --> 00:17:53,000
evaluation for

754
00:17:50,000 --> 00:17:53,000
these disorders.

755
00:17:53,000 --> 00:17:55,000
Right now this is a huge

756
00:17:53,000 --> 00:17:55,000
burden to the participant

757
00:17:55,000 --> 00:17:57,000
because they have to have

758
00:17:55,000 --> 00:17:57,000
a lumbar puncture and a

759
00:17:57,000 --> 00:17:58,000
lot of blood work.

760
00:17:58,000 --> 00:18:00,000
It's also very expensive.

761
00:18:00,000 --> 00:18:02,000
And so I'm hoping that as

762
00:18:00,000 --> 00:18:02,000
we start identifying these

763
00:18:02,000 --> 00:18:06,000
specific disorders we find

764
00:18:02,000 --> 00:18:06,000
ways to look for them and

765
00:18:06,000 --> 00:18:09,000
that this very - I think

766
00:18:06,000 --> 00:18:09,000
we have the tip of the

767
00:18:09,000 --> 00:18:11,000
iceberg here so this

768
00:18:09,000 --> 00:18:11,000
very early work.

769
00:18:11,000 --> 00:18:13,000
I hope it will come to

770
00:18:11,000 --> 00:18:13,000
fruition and we'll find

771
00:18:13,000 --> 00:18:16,000
some new things about treatment

772
00:18:13,000 --> 00:18:16,000
for refractory depression.

773
00:18:16,000 --> 00:18:18,000
I want to shift gears a

774
00:18:16,000 --> 00:18:18,000
little bit because I know

775
00:18:18,000 --> 00:18:22,000
you've done work in terms

776
00:18:18,000 --> 00:18:22,000
of suicide prevention and ask

777
00:18:22,000 --> 00:18:25,000
you how all of this fits in with

778
00:18:22,000 --> 00:18:25,000
that very important issue.

779
00:18:25,000 --> 00:18:30,000
Suicide is really what has

780
00:18:25,000 --> 00:18:30,000
driven most of my work

781
00:18:30,000 --> 00:18:32,000
because I have never seen

782
00:18:30,000 --> 00:18:32,000
a loss like somebody who's

783
00:18:32,000 --> 00:18:35,000
lost a family

784
00:18:32,000 --> 00:18:35,000
member to suicide.

785
00:18:35,000 --> 00:18:38,000
And I think that the part

786
00:18:35,000 --> 00:18:38,000
that I really want to

787
00:18:38,000 --> 00:18:41,000
communicate and - I work

788
00:18:38,000 --> 00:18:41,000
with a group that

789
00:18:41,000 --> 00:18:43,000
Sue Wesner started at the

790
00:18:41,000 --> 00:18:43,000
University of Pittsburgh

791
00:18:43,000 --> 00:18:45,000
called 'survivors of

792
00:18:43,000 --> 00:18:45,000
suicide' where we talked

793
00:18:45,000 --> 00:18:47,000
to family members who've

794
00:18:45,000 --> 00:18:47,000
lost a member of the

795
00:18:47,000 --> 00:18:49,000
family or a loved

796
00:18:47,000 --> 00:18:49,000
one to suicide.

797
00:18:49,000 --> 00:18:52,000
And I think the really

798
00:18:49,000 --> 00:18:52,000
crucial thing here is that

799
00:18:52,000 --> 00:18:56,000
we need to understand that this

800
00:18:52,000 --> 00:18:56,000
is a medical condition.

801
00:18:56,000 --> 00:18:59,000
The, the brain of someone

802
00:18:56,000 --> 00:18:59,000
who's completed suicide is

803
00:18:59,000 --> 00:19:01,000
not healthy, and

804
00:18:59,000 --> 00:19:01,000
so we're trying to apply,

805
00:19:01,000 --> 00:19:03,000
you know, healthy

806
00:19:01,000 --> 00:19:03,000
thought processes

807
00:19:03,000 --> 00:19:06,000
to what was

808
00:19:03,000 --> 00:19:06,000
happening during a

809
00:19:06,000 --> 00:19:09,000
suicide attempt or

810
00:19:06,000 --> 00:19:09,000
a suicide death.

811
00:19:09,000 --> 00:19:12,000
And I think it's really

812
00:19:09,000 --> 00:19:12,000
crucial that we understand

813
00:19:12,000 --> 00:19:15,000
that these kinds of things

814
00:19:12,000 --> 00:19:15,000
so, you know, biochemical

815
00:19:15,000 --> 00:19:16,000
changes that no one

816
00:19:15,000 --> 00:19:16,000
has any control over.

817
00:19:16,000 --> 00:19:19,000
You know structural

818
00:19:16,000 --> 00:19:19,000
changes that make a brain

819
00:19:19,000 --> 00:19:22,000
more likely to,

820
00:19:19,000 --> 00:19:22,000
to engage in suicidal

821
00:19:22,000 --> 00:19:26,000
behavior are true

822
00:19:22,000 --> 00:19:26,000
biologic phenomenon.

823
00:19:26,000 --> 00:19:31,000
And so when I see families

824
00:19:26,000 --> 00:19:31,000
grieving and nothing -

825
00:19:31,000 --> 00:19:34,000
that is for somebody who

826
00:19:31,000 --> 00:19:34,000
has died, nothing was

827
00:19:34,000 --> 00:19:36,000
done wrong, that this is

828
00:19:34,000 --> 00:19:36,000
an illness, any more than

829
00:19:36,000 --> 00:19:38,000
if somebody had a heart

830
00:19:36,000 --> 00:19:38,000
attack you would say well

831
00:19:38,000 --> 00:19:39,000
I could have prevented it.

832
00:19:39,000 --> 00:19:43,000
It's a medical condition

833
00:19:39,000 --> 00:19:43,000
and it's life threatening.

834
00:19:43,000 --> 00:19:46,000
And I do think it's

835
00:19:43,000 --> 00:19:46,000
crucial that, I'm not

836
00:19:46,000 --> 00:19:47,000
saying that this is life

837
00:19:46,000 --> 00:19:47,000
threatening and that

838
00:19:47,000 --> 00:19:50,000
people who have depression

839
00:19:47,000 --> 00:19:50,000
should not seek treatment,

840
00:19:50,000 --> 00:19:52,000
we do have good treatments

841
00:19:50,000 --> 00:19:52,000
for things, but what I

842
00:19:52,000 --> 00:19:54,000
want to say is that the

843
00:19:52,000 --> 00:19:54,000
very severe end of the spectrum

844
00:19:54,000 --> 00:19:56,000
this is a medical

845
00:19:54,000 --> 00:19:56,000
problem and we need to

846
00:19:56,000 --> 00:19:58,000
understand it better so

847
00:19:56,000 --> 00:19:58,000
we can take care of it.

848
00:19:58,000 --> 00:20:01,000
I think it's a very

849
00:19:58,000 --> 00:20:01,000
important point for

850
00:20:01,000 --> 00:20:05,000
survivors to know that

851
00:20:01,000 --> 00:20:05,000
they didn't do anything wrong.

852
00:20:05,000 --> 00:20:07,000
Their loved one had--

853
00:20:07,000 --> 00:20:07,000
-- an illness

854
00:20:07,000 --> 00:20:09,000
--an illness.

855
00:20:09,000 --> 00:20:12,000
And while most illnesses

856
00:20:09,000 --> 00:20:12,000
are treatable,

857
00:20:12,000 --> 00:20:16,000
sometimes it isn't

858
00:20:12,000 --> 00:20:16,000
successfully treated.

859
00:20:16,000 --> 00:20:18,000
And then the other

860
00:20:16,000 --> 00:20:18,000
important message is that

861
00:20:18,000 --> 00:20:21,000
if somebody is having

862
00:20:18,000 --> 00:20:21,000
thoughts of hurting themself

863
00:20:21,000 --> 00:20:24,000
they should

864
00:20:21,000 --> 00:20:24,000
immediately seek treatment.

865
00:20:24,000 --> 00:20:26,000
Right.

866
00:20:26,000 --> 00:20:27,000
Because there are

867
00:20:26,000 --> 00:20:27,000
things we can do, exactly.

868
00:20:27,000 --> 00:20:29,000
It's a chronic life

869
00:20:27,000 --> 00:20:29,000
threatening illness and

870
00:20:29,000 --> 00:20:31,000
you definitely should

871
00:20:29,000 --> 00:20:31,000
have treatment for it.

872
00:20:31,000 --> 00:20:35,000
I'm curious about going

873
00:20:31,000 --> 00:20:35,000
back to the first patient

874
00:20:35,000 --> 00:20:37,000
who was helped by this.

875
00:20:37,000 --> 00:20:41,000
Tell me how his life has changed

876
00:20:37,000 --> 00:20:41,000
as a result of the treatment.

877
00:20:41,000 --> 00:20:44,000
So when I was taking

878
00:20:41,000 --> 00:20:44,000
care of him he was being

879
00:20:44,000 --> 00:20:46,000
repeatedly hospitalized

880
00:20:44,000 --> 00:20:46,000
so much that he couldn't

881
00:20:46,000 --> 00:20:47,000
attend high school.

882
00:20:47,000 --> 00:20:50,000
And when he started

883
00:20:47,000 --> 00:20:50,000
responding to the

884
00:20:50,000 --> 00:20:53,000
replacement therapy he was

885
00:20:50,000 --> 00:20:53,000
able to graduate and he

886
00:20:53,000 --> 00:20:55,000
went to college and

887
00:20:53,000 --> 00:20:55,000
he's actually an

888
00:20:55,000 --> 00:20:58,000
environmental scientist now and

889
00:20:55,000 --> 00:20:58,000
he's in a healthy relationship

890
00:20:58,000 --> 00:21:00,000
and he's happy.

891
00:21:00,000 --> 00:21:02,000
There are days that depression

892
00:21:00,000 --> 00:21:02,000
will still be present

893
00:21:02,000 --> 00:21:06,000
but nothing like what

894
00:21:02,000 --> 00:21:06,000
he came from.

895
00:21:06,000 --> 00:21:11,000
And he talks about, you

896
00:21:06,000 --> 00:21:11,000
know, trying to learn how,

897
00:21:11,000 --> 00:21:13,000
how to live because he

898
00:21:11,000 --> 00:21:13,000
had never planned to get

899
00:21:13,000 --> 00:21:16,000
beyond the age of 20.

900
00:21:16,000 --> 00:21:21,000
And so it was really a

901
00:21:16,000 --> 00:21:21,000
fascinating change to watch.

902
00:21:21,000 --> 00:21:22,000
And I've seen it with

903
00:21:21,000 --> 00:21:22,000
other patients too.

904
00:21:22,000 --> 00:21:25,000
We had another young woman

905
00:21:22,000 --> 00:21:25,000
with the same disorder who

906
00:21:25,000 --> 00:21:28,000
had a second medical

907
00:21:25,000 --> 00:21:28,000
illness that was life

908
00:21:28,000 --> 00:21:31,000
threatening and she would

909
00:21:28,000 --> 00:21:31,000
allow that medical illness

910
00:21:31,000 --> 00:21:34,000
to get out of control because

911
00:21:31,000 --> 00:21:34,000
she didn't want to be alive.

912
00:21:34,000 --> 00:21:37,000
And so she has also shown

913
00:21:34,000 --> 00:21:37,000
significant improvement

914
00:21:37,000 --> 00:21:39,000
and being able to go

915
00:21:37,000 --> 00:21:39,000
to college which was

916
00:21:39,000 --> 00:21:43,000
something I think she and

917
00:21:39,000 --> 00:21:43,000
her family didn't expect.

918
00:21:43,000 --> 00:21:45,000
So basically people are

919
00:21:43,000 --> 00:21:45,000
able to have their life

920
00:21:45,000 --> 00:21:48,000
back as a result

921
00:21:45,000 --> 00:21:48,000
of this.

922
00:21:48,000 --> 00:21:51,000
And it's been, it's been

923
00:21:48,000 --> 00:21:51,000
really challenging because

924
00:21:51,000 --> 00:21:54,000
we have patients coming

925
00:21:51,000 --> 00:21:54,000
to us on referral for the

926
00:21:54,000 --> 00:21:59,000
study and, you know, we

927
00:21:54,000 --> 00:21:59,000
just with, with some

928
00:21:59,000 --> 00:22:01,000
private funds, I'm

929
00:21:59,000 --> 00:22:01,000
incredibly thankful for

930
00:22:01,000 --> 00:22:04,000
the funding we have - the

931
00:22:01,000 --> 00:22:04,000
Children's Hospital Foundation

932
00:22:04,000 --> 00:22:07,000
and an anonymous donor

933
00:22:04,000 --> 00:22:07,000
has given us funds,

934
00:22:07,000 --> 00:22:08,000
and with some

935
00:22:07,000 --> 00:22:08,000
private funds we've been

936
00:22:08,000 --> 00:22:10,000
able to study

937
00:22:08,000 --> 00:22:10,000
young adults.

938
00:22:10,000 --> 00:22:13,000
But I just had a 70 year

939
00:22:10,000 --> 00:22:13,000
old man come to the study

940
00:22:13,000 --> 00:22:15,000
who has been ill since he

941
00:22:13,000 --> 00:22:15,000
was eight years old and he's

942
00:22:15,000 --> 00:22:18,000
asking me like "if I have

943
00:22:15,000 --> 00:22:18,000
one of these disorders."

944
00:22:18,000 --> 00:22:21,000
And his profile fits

945
00:22:18,000 --> 00:22:21,000
exactly what we see.

946
00:22:21,000 --> 00:22:23,000
"You know I'd like to have

947
00:22:21,000 --> 00:22:23,000
another I'd like to have

948
00:22:23,000 --> 00:22:24,000
"10 years where I feel OK."

949
00:22:24,000 --> 00:22:26,000
And it's heartbreaking

950
00:22:24,000 --> 00:22:26,000
you know.

951
00:22:26,000 --> 00:22:30,000
It really is devastating

952
00:22:26,000 --> 00:22:30,000
when depression is

953
00:22:30,000 --> 00:22:33,000
untreated or not

954
00:22:30,000 --> 00:22:33,000
successfully treated.

955
00:22:33,000 --> 00:22:36,000
I think an important point

956
00:22:33,000 --> 00:22:36,000
is while you are focusing

957
00:22:36,000 --> 00:22:39,000
on that 15% to have

958
00:22:36,000 --> 00:22:39,000
refractory depression--

959
00:22:39,000 --> 00:22:39,000
there are so

960
00:22:39,000 --> 00:22:39,000
many more.

961
00:22:39,000 --> 00:22:41,000
--Right.

962
00:22:41,000 --> 00:22:44,000
And the vast majority

963
00:22:41,000 --> 00:22:44,000
of people do respond to

964
00:22:44,000 --> 00:22:47,000
current treatments,

965
00:22:44,000 --> 00:22:47,000
medications, talk therapy,--

966
00:22:47,000 --> 00:22:50,000
-- and shouldn't suffer

967
00:22:47,000 --> 00:22:50,000
depression because

968
00:22:50,000 --> 00:22:53,000
depression takes away your

969
00:22:50,000 --> 00:22:53,000
interpersonal relationships,

970
00:22:53,000 --> 00:22:58,000
your, your goals,

971
00:22:53,000 --> 00:22:58,000
your ability to move forward.

972
00:22:58,000 --> 00:22:59,000
It really takes

973
00:22:58,000 --> 00:22:59,000
everything.

974
00:22:59,000 --> 00:23:01,000
And it's really important

975
00:22:59,000 --> 00:23:01,000
that people get treatment.

976
00:23:01,000 --> 00:23:04,000
I want to shift gears for

977
00:23:01,000 --> 00:23:04,000
a couple of minutes and

978
00:23:04,000 --> 00:23:08,000
ask you about - as a young

979
00:23:04,000 --> 00:23:08,000
researcher a person who's

980
00:23:08,000 --> 00:23:11,000
focused on clinical

981
00:23:08,000 --> 00:23:11,000
care and also research,

982
00:23:11,000 --> 00:23:14,000
improving clinical care.

983
00:23:14,000 --> 00:23:18,000
What's it like for you

984
00:23:14,000 --> 00:23:18,000
to pursue a career in research?

985
00:23:18,000 --> 00:23:20,000
It can be really

986
00:23:18,000 --> 00:23:20,000
challenging.

987
00:23:20,000 --> 00:23:22,000
Thank you for asking.

988
00:23:22,000 --> 00:23:25,000
The thing that really

989
00:23:22,000 --> 00:23:25,000
keeps me going are the

990
00:23:25,000 --> 00:23:28,000
patients I take care of because

991
00:23:28,000 --> 00:23:31,000
depression is a horrible thing

992
00:23:28,000 --> 00:23:31,000
but people that suffer with it

993
00:23:31,000 --> 00:23:33,000
have an incredible

994
00:23:31,000 --> 00:23:33,000
understanding of what it

995
00:23:33,000 --> 00:23:36,000
means to be alive and what

996
00:23:33,000 --> 00:23:36,000
the challenges are of

997
00:23:36,000 --> 00:23:39,000
being here on this planet

998
00:23:36,000 --> 00:23:39,000
and it's, it's amazingly

999
00:23:39,000 --> 00:23:41,000
inspiring how they fight

1000
00:23:39,000 --> 00:23:41,000
this illness

1001
00:23:41,000 --> 00:23:42,000
and how they get better.

1002
00:23:42,000 --> 00:23:46,000
So that part means

1003
00:23:42,000 --> 00:23:46,000
I'm steadfast.

1004
00:23:46,000 --> 00:23:49,000
But if it weren't for it

1005
00:23:46,000 --> 00:23:49,000
- seriously if it weren't

1006
00:23:49,000 --> 00:23:50,000
for private foundations

1007
00:23:49,000 --> 00:23:50,000
like the

1008
00:23:50,000 --> 00:23:51,000
Brain and Behavior

1009
00:23:50,000 --> 00:23:51,000
Research Foundation,

1010
00:23:51,000 --> 00:23:53,000
the American Foundation for

1011
00:23:51,000 --> 00:23:53,000
Suicide Prevention,

1012
00:23:53,000 --> 00:23:57,000
and private donors, I wouldn't

1013
00:23:53,000 --> 00:23:57,000
be able to keep this going.

1014
00:23:57,000 --> 00:23:59,000
And so there are days I

1015
00:23:57,000 --> 00:23:59,000
am concerned about that.

1016
00:23:59,000 --> 00:24:02,000
The amount of money

1017
00:23:59,000 --> 00:24:02,000
that's dedicated toward

1018
00:24:02,000 --> 00:24:05,000
depression and suicide

1019
00:24:02,000 --> 00:24:05,000
prevention in this country

1020
00:24:05,000 --> 00:24:06,000
in research is

1021
00:24:05,000 --> 00:24:06,000
very minuscule.

1022
00:24:06,000 --> 00:24:10,000
And I think we need to

1023
00:24:06,000 --> 00:24:10,000
talk more about the fact

1024
00:24:10,000 --> 00:24:13,000
that this is, this is the

1025
00:24:10,000 --> 00:24:13,000
disease that causes the

1026
00:24:13,000 --> 00:24:16,000
most disability and we

1027
00:24:13,000 --> 00:24:16,000
need to address it.

1028
00:24:16,000 --> 00:24:19,000
I think that's a very

1029
00:24:16,000 --> 00:24:19,000
important issue that you

1030
00:24:19,000 --> 00:24:22,000
bring up that lives can be

1031
00:24:19,000 --> 00:24:22,000
changed by, one,

1032
00:24:22,000 --> 00:24:26,000
making sure people have access

1033
00:24:22,000 --> 00:24:26,000
to appropriate treatment and,

1034
00:24:26,000 --> 00:24:29,000
two, making sure that we

1035
00:24:26,000 --> 00:24:29,000
fund research so that new

1036
00:24:29,000 --> 00:24:32,000
and even better treatments

1037
00:24:29,000 --> 00:24:32,000
are available to people.

1038
00:24:32,000 --> 00:24:34,000
And as you see one

1039
00:24:32,000 --> 00:24:34,000
individual improve from

1040
00:24:34,000 --> 00:24:37,000
this illness it affects

1041
00:24:34,000 --> 00:24:37,000
everyone that they

1042
00:24:37,000 --> 00:24:39,000
interact with, their,

1043
00:24:37,000 --> 00:24:39,000
their children,

1044
00:24:39,000 --> 00:24:41,000
their family members,

1045
00:24:39,000 --> 00:24:41,000
the people they teach.

1046
00:24:41,000 --> 00:24:42,000
So it really does.

1047
00:24:42,000 --> 00:24:45,000
It's very rewarding to take care

1048
00:24:42,000 --> 00:24:45,000
of people with this illness.

1049
00:24:45,000 --> 00:24:48,000
Lisa I want to thank you

1050
00:24:45,000 --> 00:24:48,000
so very much for joining

1051
00:24:48,000 --> 00:24:51,000
us today and more

1052
00:24:48,000 --> 00:24:51,000
importantly the work that

1053
00:24:51,000 --> 00:24:54,000
you've done to help

1054
00:24:51,000 --> 00:24:54,000
change the field,

1055
00:24:54,000 --> 00:24:56,000
change people's lives,

1056
00:24:54,000 --> 00:24:56,000
and the work that you're going

1057
00:24:56,000 --> 00:24:58,000
to do in the years ahead.

1058
00:24:58,000 --> 00:24:59,000
Thank you so much

1059
00:24:58,000 --> 00:24:59,000
for having me here.

1060
00:24:59,000 --> 00:25:00,000
Thank you.

1061
00:25:03,000 --> 00:25:05,000
If you have depression

1062
00:25:03,000 --> 00:25:05,000
don't suffer in silence.

1063
00:25:05,000 --> 00:25:07,000
Seek help.

1064
00:25:07,000 --> 00:25:11,000
And if your depression does not

1065
00:25:07,000 --> 00:25:11,000
get better with treatment

1066
00:25:11,000 --> 00:25:12,000
do not give up.

1067
00:25:12,000 --> 00:25:17,000
Even people with refractory

1068
00:25:12,000 --> 00:25:17,000
depression get better.

1069
00:25:17,000 --> 00:25:18,000
As a result of cutting

1070
00:25:17,000 --> 00:25:18,000
edge research

1071
00:25:18,000 --> 00:25:22,000
with help, there truly is hope.

1072
00:25:22,000 --> 00:25:25,000
Until next time,

1073
00:25:22,000 --> 00:25:25,000
I'm Dr. Jeff Borenstein.

1074
00:25:25,000 --> 00:25:27,000
Goodbye.

1075
00:25:27,000 --> 00:25:36,000
♪♪

1076
00:25:36,000 --> 00:25:37,000
(Dr. Borenstein)

1077
00:25:36,000 --> 00:25:37,000
Do not suffer in silence.

1078
00:25:37,000 --> 00:25:40,000
With help, there is hope.

1079
00:25:40,000 --> 00:25:44,000
Healthy Minds is brought

1080
00:25:40,000 --> 00:25:44,000
to you in part by:

1081
00:25:44,000 --> 00:25:47,000
The American Psychiatric

1082
00:25:44,000 --> 00:25:47,000
Association Foundation.

1083
00:25:49,000 --> 00:25:53,000
The Graham Boeckh

1084
00:25:49,000 --> 00:25:53,000
Foundation.

1085
00:25:53,000 --> 00:25:57,000
And the New York State

1086
00:25:53,000 --> 00:25:57,000
Office of Mental Health.

1087
00:25:57,000 --> 00:26:04,000
♪♪

1088
00:26:04,000 --> 00:26:07,000
If you would like to watch

1089
00:26:04,000 --> 00:26:07,000
our expert interview in

1090
00:26:07,000 --> 00:26:12,000
its entirety log onto bbr

1091
00:26:07,000 --> 00:26:12,000
foundation dot org slash

1092
00:26:12,000 --> 00:26:13,000
Healthy Minds.

1093
00:26:13,000 --> 00:26:44,000
♪♪