Yale Psychiatry Grand Rounds: January 15, 2021

January 15, 2021

Information

"Clinical Applications of Psychiatric Genetics: Improving Patient Outcomes Through Psychiatric Genetic Counseling"

Jehannine Austin, PhD, Professor, Department of Medical Genetics, The University of British Columbia

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00:00Thank you and welcome everyone before
00:02we begin this morning's grounds,
00:03I want to take a moment and
00:05acknowledge the ongoing events that
00:07are taking place in Washington DC.
00:09Last week, a group of insurrectionist
00:11marched on our nation's capital attempted
00:13to undermine our constitutional process,
00:15destroying federal property
00:16and murdered a police officer.
00:18Some of these individuals did so openly
00:20under the banner of a white nationalist
00:23and white supremacist organization.
00:25The images that it's insurgent
00:26mob are indelibly seared into
00:27our collective consciousness,
00:29including the Confederate flag
00:30waving within our capital in
00:31the details that are emerging,
00:33such as the removal of panic buttons
00:35from Congresswoman Presley's
00:36office prior to the attack.
00:38Patient even darker picture of what occurred.
00:41Well, all of us hope for a speedy
00:43and safe transition of power.
00:44I want to acknowledge that many
00:45of us may be traumatized and just
00:47say if you're in need of support,
00:49please reach out to Cindy Crew Stoehr to
00:50other members of our Department leadership.
00:56I think we'll laugh, pause.
01:04And then welcome again if we can try
01:07to put this all aside and be present
01:09for a little bit in a different space,
01:12acknowledging that that may be hard.
01:16It also gives me great pleasure
01:17to be able to introduce a friend
01:20this morning, Janine Austin.
01:21Janine is the executive director of
01:22the BC Mental Health and Substance
01:24Use Services Research Institute to
01:26professor in psychiatry medical genetics
01:28at the University of British Columbia,
01:30where she holds the Canada Research Chair
01:32in Translational Psychiatric Genomics,
01:33who research involves studying the impact
01:35of genetic counseling for people with
01:37psychiatric disorders in their families.
01:38She founded the world's first specialist
01:40psychiatric genetic counseling
01:42service that is when an award for
01:43its impact on patient outcomes,
01:45in addition to peer reviewed publications,
01:46she's written a book.
01:48One awards for teaching leadership
01:49and research.
01:50She's a member of the College of the
01:52Royal Society of Canada and a Fellow of
01:54the Canadian Academy of Health Sciences.
01:56Through my work with her on
01:57the ISP G Education Committee,
01:59I can also attest that she is
02:01an extraordinary educator and
02:02a wonderful colleague.
02:03Please join me in welcoming Janine Austin.
02:07Thanks so much David. Yeah and yeah,
02:09so I'm based in Vancouver, Canada.
02:11As you just heard and so I've been
02:13watching events South of the border here
02:15with great consternation and concern.
02:17So thank you very much for that opening
02:20David and I will do my best over the
02:22next little bit of time that we get
02:25to spend together to provide a bit of.
02:28Distraction entertainment even
02:29yeah so thank you for that.
02:31Yeah and I think you know in the
02:34spirit of that sort of thing I'd like
02:36to begin by acknowledging that I'm
02:39speaking to you today from Vancouver,
02:41which is actually the traditional
02:43unceded ancestral territories
02:44of the Coast Salish peoples.
02:46And that actually includes the Musqueam's,
02:48Squamish and slavers, who's nations?
02:50So as a as a as a settler who's
02:53learning and wanting to sort of
02:56uphold and protect and celebrate the.
02:58Indigenous peoples of this country.
02:59I think it's just important that
03:02you know to acknowledge that that
03:04this is where I am at at the moment.
03:06OK, so I'm going to see if I can
03:09screen share with you all so that you
03:11can look at my delightfull slides.
03:14Hang on one second and so also
03:16just just in in disclosures.
03:18It's just past 7:00 AM here and I am not
03:21necessarily the world's best morning person.
03:24So if I start mixing my words up,
03:27please be please be gentle with me.
03:31OK, here we go,
03:31so hopefully you can see my title slide.
03:33David,
03:33can you give me a thumbs up if you can.
03:36Perfect thank you.
03:37OK,
03:38so um,
03:38I would like to talk to you this
03:41morning about clinical applications
03:42of psychiatric genetics and
03:44specifically psychiatric genetic
03:46counseling in relation to that.
03:48Yeah, so before we get going at all,
03:51I have no financial interest
03:53in any commercial entity that
03:55gets mentioned or not today.
03:57Yeah so.
03:59And what I thought I'd like to talk
04:01with you about today is basically
04:02just to ensure that we're all starting
04:05from the same place together by
04:07reviewing what we currently know about
04:09genetics with psychiatric disorders.
04:10I'm going to keep it super high level
04:12and super Brief because I want to
04:14retain most of the time that we have
04:17to talk about the more substantive
04:19or meaty important pieces which would
04:21be discussing how important it is
04:23for families to understand what the
04:24causes of psychiatric disorders and
04:26to discuss the outcomes of genetic
04:28counseling for psychiatric disorders.
04:29And to consider what the implications
04:32of that might mean for applying genetic
04:35testing in this context basically.
04:37Yeah,
04:38so let's start at the beginning
04:40because that is usually a good place
04:43to start with reviewing what we know
04:46about the genetics of these conditions.
04:49And this is really for my
04:51amusement more than anything else.
04:54So it's a cartoon of, you know,
04:57scientist standing around a jigsaw
04:59puzzle with three billion pieces saying
05:01I think I found a corner piece and
05:04for the longest time this really did
05:06very accurately represent where we
05:08were at in terms of understanding the
05:10genetics of psychiatric disorders.
05:12I do like to think that we've come
05:14a little way since since since this
05:16really didn't capture in encapsulate
05:18everything between you and so this,
05:21this is, I think one of the you know.
05:24Celebrated images in the psychiatric
05:26genetics community and so for
05:28those of you in the know.
05:29This is a Manhattan plot.
05:31For those of you don't
05:33really know what it is.
05:35Basically it's a way of
05:36representing Association studies.
05:37So along the X axis,
05:39you're looking at chromosome
05:41number and along the Y axis.
05:43It's like the degree of statistical
05:45significance of Association of a variant
05:47with the the condition of interest.
05:49So the higher the peak that you see,
05:52the more significant the P value essentially.
05:55And anything that surpasses that
05:56red horizontal line that you can see
05:59there at the bottom is a value that
06:01surpasses genome wide significance.
06:03So it is called a Manhattan plot,
06:05because theoretically, these are.
06:07These pictures are supposed to
06:08look like the Manhattan skyline.
06:10You know, lots of very tall buildings,
06:13lots of Rachel peaks.
06:14So the sad,
06:15sad little joking psychiatric genetics
06:17community for for many years was
06:19that we didn't have Manhattan plots.
06:21We had Omaha plots because
06:23there weren't any peaks.
06:24It was all.
06:25Latin music anyway,
06:26so this image is so celebrated because
06:29it was basically the first one
06:31where they were really any number of
06:33substantive peaks above that red line, right?
06:36So nowadays,
06:36so you'll see from the date at the top there.
06:40This is from 2014,
06:41and so nowadays,
06:42as my PhD supervisor maker Donovan
06:44likes to say it's just taller,
06:47greener and denser.
06:47So it's just a lot more of those
06:50variants that are surpassing
06:51that threshold for genome wide
06:53significance nowadays, but yeah.
06:55And I know your eyes are all going to
06:57that really tall one in the middle and going.
07:00What is that?
07:01I know they are.
07:02That's that's the major
07:03histocompatibility complex.
07:04And so just so that you know,
07:06the tallness of the peak does not
07:08mean it plays a big, big role.
07:10It just means it's more significant.
07:12So that's all that means.
07:14So anyway,
07:15that's all the single nucleotide stuff,
07:17so they're really really tiny tiny
07:18variants that can contribute to the
07:20development of psychiatric disorders.
07:22But there's also more than that, of course.
07:24So what you're looking at in this table
07:26is different types of variations,
07:28genetic variations, that is,
07:30that can contribute to psychiatric
07:31illness in blue.
07:32We're looking at those single
07:34nucleotide polymorphism is basically
07:35the things that were just showing
07:37up on that Manhattan plot.
07:38So each one of those peaks would
07:40be one of these rows essentially,
07:42and what you can see is that those
07:45variations are.
07:46Really common in the population,
07:47but they only make a tiny difference
07:49to whether to your vulnerability for
07:51developing one of these disorders,
07:54but at the top you've got a
07:55few lines in purple and these
07:57represent copy number variations,
07:59so these are bigger duplications
08:01or deletions of genetic material.
08:03The most famous most well known of
08:05which I think in psychiatric spaces.
08:07Of course, 22 Q.
08:0911, deletion an.
08:10So what you can see with these
08:12is that they are considerably
08:14less common in the population.
08:16But when you have one,
08:18it makes a much bigger difference.
08:20Much bigger contribution to your
08:21vulnerability for developing
08:22one of these conditions,
08:24couple of things to draw your attention
08:26to is that although not all of the
08:29lines have multiple disorders listed
08:31in them in that second column,
08:33I think it's very fair to say that they
08:36they shouldn't need to update this slide.
08:39Essentially that they should have,
08:40so the variations don't seem to
08:42to contribute to risk for only
08:44one specific discrete condition.
08:46Instead,
08:47it seems that genetic variation
08:49contributes to one's vulnerability
08:51for developing mental illness broadly.
08:53And perhaps it depends what particular
08:56combination of things you've got
08:59going on that determines what
09:01actual diagnosis one might receive.
09:04So that was a very brief whistle.
09:06Stop tour about what it is we
09:08currently understand about the
09:09genetics of psychiatric disorders.
09:10I want to contextualize that
09:12for you because I don't.
09:13I know you will know this,
09:15but it's just good to say explicitly.
09:17Again,
09:17these are not conditions that
09:18caused by genetic variation alone.
09:20To the best of our knowledge, right?
09:22So we know that from twin studies, right?
09:24So if a condition was entirely
09:26caused by genetics,
09:26we would know that because
09:28we'd see the identical twin
09:29concordance rate would be 100%.
09:31And of course,
09:31we don't see that for
09:33any of these conditions.
09:35However,
09:35what we do see is that the core
09:37concordance rates for psychiatric
09:38disorders are higher amongst identical
09:40Twins than they are amongst non identical,
09:42which is what the classic
09:44hallmarks that we look for.
09:45If we need to to determine whether
09:47or not genetics is a contributor.
09:49So genetics is a contributor,
09:51yes, but it's not the only thing,
09:53so I think that's just really
09:56important contextual framing here.
09:57So where does that leave us in terms of,
09:59you know if we're thinking?
10:00About genetic applications and
10:01for psychiatric disorders,
10:02the first thing that we tend to think
10:05about is genetic testing, right?
10:06So yeah,
10:07there's no genetic test with
10:08which to establish, confirm,
10:10or refine a psychiatric diagnosis.
10:12That's just where we're at.
10:13And honestly,
10:14there's not really gonna be becausw.
10:16These aren't conditions that are
10:17caused entirely by genetics,
10:19so you know,
10:19we've got really important role for
10:21our experiences on the environment.
10:23If you'd prefer to put it that way.
10:27So, so secondarily,
10:28family history is used clinically
10:29at the moment for predicting
10:31risk for psychiatric illness.
10:32Polygenic risk scores,
10:33which, if we've got time,
10:35I'd like to touch on at the end,
10:37or matter really hot debate at the moment,
10:40but they're actually already available
10:41on in a director consumer fashion.
10:43In fact, I got an email This morning from a
10:46gentleman sending me his polygenic risk score
10:48for bipolar disorder and asking, you know,
10:51if we could talk about it because he wants
10:54to understand more about what that means.
10:57So yeah, this is this is a a clinical
11:00reality at the moment and then copy number
11:02variation which we just briefly talked about.
11:0522 Q for example.
11:06So testing for those kinds of things is of
11:09the most utility in the context of family
11:11members of people known to carry them,
11:14or people who have psychiatric illness and
11:15other problems and multisystem conditions.
11:17But there's a movement in
11:19the literature at the moment.
11:20An argument that people are making that
11:22maybe we should be thinking about screening
11:24for CN bees and everybody with schizophrenia,
11:27let's say.
11:28So there are clinical practice guidelines
11:30suggesting that that's as you will know,
11:32that that that that's first here
11:34test in the context of autism,
11:36but but what about schizophrenia?
11:37Maybe maybe we should be doing it there.
11:40Some people are arguing.
11:41And then just very briefly to mention,
11:44because it is a type of genetic
11:46testing that relates to psychiatric
11:48disorders pharmacogenetic testing.
11:49Obviously,
11:50you know,
11:50in the in the psychiatric space this
11:53is an intense interest just because
11:55of the clinical issues that we know.
11:57Trial and errors going through,
11:59you know psychiatric medication
12:00trials can be just very,
12:02very difficult for all involved.
12:03Clinicians and patients like and
12:05so wouldn't it be nice if we could
12:08do a genetic test to predict?
12:10You know what would work best?
12:12Best for somebody with the least
12:14side effects.
12:14And so yeah,
12:15this is a very very active area
12:17of work at the moment of course.
12:19So yeah,
12:20and that's really all I'm going
12:21to say about that,
12:22but I think it's just important
12:24to acknowledge so, given that,
12:26given that there isn't any genetic testing,
12:28I've just told you what,
12:29is there anything that we can do like what?
12:31Why am I even talking to you this morning?
12:34Like surely we should just hang up now,
12:36right? No no, stay with me please.
12:38So because genetic counseling
12:39is not genetic testing OK,
12:41I I know that there's a sort of a popular
12:43conception that genetic counseling is
12:45something that we do for pregnant.
12:47In an you know,
12:48or if you're going to get BRCA
12:50testing or something like that.
12:51And of course you know you can
12:53kind of definitely apply genetic
12:55counseling in those contexts,
12:56but that's like the tip of the iceberg.
12:58Really, there's way more to it than that.
13:02So I'm going to tell it like this.
13:04This sounds really trivial and boring,
13:06but hopefully I'm going to illustrate
13:08for you later why it's not OK.
13:10So understanding that psychiatric disorders
13:12are themselves not usually inherited,
13:13but what that we can we can inherit
13:15is a vulnerability to psychiatric
13:17illness that can actually be a
13:19profoundly powerful thing for people
13:21with these conditions in their
13:23families to hear about. And again,
13:25I'm going to illustrate that for you later,
13:27understanding that its genes and
13:29environment that usually work
13:30together to produce illness to you.
13:32That may sound very trivial.
13:34To me it did initially,
13:35but my experience of like working
13:37with families and helping them to
13:39understand that shows me that from
13:40the family experience perspective,
13:42this is not trivial at all.
13:45And then of course it's called
13:47genetic counseling and so counseling
13:49around the emotional issues that
13:52typically attach to explanations
13:54for cause of illness is critical.
13:56So we're talking about things like guilt,
13:59blame, shame, fear, stigma,
14:00all of that good stuff.
14:02Well, not good stuff, terrible stuff.
14:05But counseling around those issues
14:08can be profoundly impactful.
14:10So let's talk a little bit
14:12about more that stuff.
14:13Let's talk more about the importance
14:14of families of understanding cause,
14:16and I'm just going to
14:17share some quotes with you,
14:18actually,
14:19and this is going to be absolutely
14:20familiar to all of you that practice
14:22clinically or ever have, right?
14:24So you know.
14:24But just to put them out there, because
14:27I think it's important grounding for us.
14:29Alright, so there's this thought.
14:30There's always that thought that
14:31maybe you're just a bad person.
14:33Maybe you're just lazy.
14:36With mental illness,
14:36it's so hard to know what you did wrong,
14:39right?
14:39So the assumption there is
14:40that you did something wrong,
14:42but it's your fault somehow, right?
14:45And then so that was people who live
14:47with psychiatric disorders themselves.
14:48But of course psychiatric
14:49disorders affect families.
14:50And so I I've spent a lot
14:52of time at this point,
14:53working with families,
14:54and I have yet to meet a parent
14:56of a child with a psychiatric
14:58disorder that doesn't feel like
15:00it was their fault in some way.
15:01And that can be for different reasons.
15:03I'm going to illustrate two of those here,
15:05so this is a quote from a mother
15:07of a child with Asperger syndrome,
15:09but it could be a mother of a child with
15:12any or father for that matter condition.
15:14So she says.
15:15The feeling that we somehow
15:16cause this is strong.
15:17This happens because we are judged
15:19harshly due to our child's behaviors.
15:21I was lectured by family members
15:23about her parenting skills.
15:25So she's feeling guilty about parenting,
15:26you know?
15:27So people judging her and thinking that
15:29you know because she's not a good parent.
15:31That's why her child has stuff.
15:33But people also feel guilty about genetics,
15:34as illustrated by this quote.
15:36It came from my side.
15:37I've got the guilt.
15:38If I hadn't had him,
15:40he wouldn't be like that.
15:41If I'd known more at the time,
15:43I probably wouldn't have had
15:44any children because of what
15:46I've seen happen to him.
15:47I didn't think about this
15:48being passed on when I
15:50was 23 years old.
15:51You think this will never happen to me,
15:53so this father doesn't have bipolar himself,
15:55but his his child does.
15:57And when it emerged in his child,
15:59the first thing that he thought was Oh
16:01my God, this is what aren't Rose had.
16:03This is exactly the same symptoms
16:05and so therefore it's my fault for
16:07passing on bad genes, quote unquote.
16:09So there's all sorts of ways
16:11in which people's explanations
16:12for cause of illness have,
16:13like really profound impact
16:15on how they feel about.
16:16And as I hope to show you later,
16:19how they react to having one of
16:21these conditions in the family.
16:23So how does this relate to
16:25genetic counseling?
16:26Well, I'd like to share with you the
16:29definition of genetic counseling from the
16:31world's largest and oldest professional
16:33Association for genetic counselors,
16:35of which I'm an ex president.
16:38So the it's actually defined as a
16:40process of helping people to understand.
16:43Yes, information and adapt
16:44counseling to the medical,
16:46psychological,
16:46and familial implications of genetic
16:48contributions to disease right
16:50doesn't say anything about pregnancy.
16:52Doesn't say anything about genetic testing.
16:54Either it's talking about helping people
16:56understand and adapt to these things,
16:59and so I'm a bit of a like a.
17:03I don't know if Heretic is the right word,
17:06but I I like to push boundaries and to
17:09encourage people to think about things
17:11in different and challenging ways and to me,
17:14this definition of genetic counseling
17:15fits beutifully underneath the
17:17umbrella definition of psychotherapy.
17:19Um, so you know,
17:20and you can read the definition
17:22for yourself here,
17:23but this is the definition from the
17:26American Psychological Association from 1990.
17:27And so you know,
17:29people like to.
17:30Think about psychotherapy as necessitating
17:33long-term relationships with people.
17:34Or,
17:35you know,
17:35people tend to think that
17:37psychotherapy equals psychoanalysis
17:38or psychodynamic therapy,
17:40or something like that,
17:42which of course it isn't.
17:44So I see,
17:45genetic counseling is a very circumscribed,
17:47time limited form of psychotherapy.
17:49But we can argue that at the end,
17:53if you'd like to.
17:56Anyway,
17:56so so so just to give you a
17:58bit of a grounding here.
18:00So what do we actually do in genetic
18:02counseling?
18:02Well really,
18:03it's about helping people to make
18:05meaning to make meaning of how,
18:06not just tell them information
18:08about how genes and experiences
18:09act together to contribute to the
18:11development of these conditions.
18:12And we've developed a visual analogy,
18:14but we found to be profoundly
18:16helpful for people,
18:16and I'm sharing that with you here.
18:18So the concept is that everybody
18:20has a mental illness jar and that
18:22there are two different types
18:24of vulnerability factor that
18:25you can use to fill your jar.
18:27Those genetic factors which
18:28are represented here.
18:29By the orange balls and
18:31environmental vulnerability factors,
18:32which are represented here by
18:34the Blue Pyramids.
18:36And we talk about how an episode
18:38of mental illness happens when
18:39the jar fills all the way to
18:41the top essentially right.
18:42So you can see in this picture
18:44that the amount
18:45of genetic vulnerability
18:46stays the same overtime,
18:47which reflects what we know from real.
18:49You know, from the research that's been done,
18:52but what can change over time is how much of
18:54that environmental vulnerability in the jar.
18:56So obviously, if you've got a CMB going on,
18:59we have different pictures that
19:00represent that as a larger orange ball.
19:02And if we're talking about
19:04large environmental stresses,
19:05covid for example.
19:06We have a version where we've got
19:08a large pyramid in the job, right?
19:10So so there's all sorts of different
19:12ways of making this really
19:13meaningful and personalized for
19:15people search up circumstances.
19:17We talk with people about how everyone has
19:18some genetic vulnerability to mental illness.
19:20Um, a few of us are going
19:22to have very little.
19:23Few of us are going to have an awful lot.
19:26Most of us are gonna actually
19:28be somewhere in the middle.
19:29I mean,
19:30that's really what we know from the
19:31Genome Wide Association studies that
19:33most of these single nucleotide
19:35polymorphism's are so common in
19:36the population that we're all
19:37going to have some of them,
19:39so that may again sounds trivial,
19:40but for people who live
19:42with these conditions,
19:43that can be revolutionary, you know.
19:44So you mean that I'm not just
19:46biologically defective in some way.
19:48You know that kind of idea,
19:50so it can be profoundly
19:51destigmatizing for people to hear
19:53this and to really integrate it.
19:55But for me,
19:56the best part about genetic counseling
19:58for psychiatric disorders is that.
20:00You don't just get to talk
20:02about how people get sick,
20:04which is what happens if you're
20:05counseling about huntingtons or
20:07Down syndrome or cystic fibrosis.
20:08In the context of psychiatric disorders,
20:10we get to talk about how people
20:13can get better.
20:14So in the context of this John model,
20:16the way the way that we talk
20:18about it is that you can't change
20:20the genetic stuff in your job.
20:22That's what this picture is representing,
20:24and there may be some things that
20:26you can do to remove some of the
20:28environmental stuff, like for example,
20:30if you're smoking an awful lot of cannabis.
20:32Let's say that is within your.
20:34Theoretically,
20:35at least that's within your
20:36control occasionally.
20:37If you're in an incredibly stressful
20:39environment that's contributing to
20:40your negative mental well being,
20:41it may be possible to remove that.
20:44Maybe, but acknowledging that can
20:46be incredibly hard,
20:47but it's possible.
20:48But in addition to that,
20:49like in the third picture that
20:51you're looking at the final panel,
20:53the jar actually has two
20:55rings sticking on top of it,
20:57and what they're doing is making
20:59the job taller so that it can
21:01accommodate more of that environmental
21:03stressor stuff without getting full.
21:05So we talk with people about sleep,
21:07exercise, social support,
21:08nutrition,
21:08finding more effective ways to
21:10manage stress as protective factors,
21:12and of course for people who've
21:14had a diagnosis medication can
21:16play a really important role.
21:17As a protective factor,
21:19we also help people to identify
21:20the more sort of individual level
21:22things that might work for them.
21:24Spending time with a pet.
21:27You know mindfulness meditation,
21:28which doesn't work for me and I'm happy to
21:31tell you about why later if you'd like.
21:33But basically it triggered the panic
21:34attack 'cause everybody else looked so
21:36peaceful and serene and I couldn't stop
21:38the thoughts coming through my head.
21:40So yeah, didn't work great for me,
21:42but so many people over the years have
21:44told me that it really works for them.
21:46So it's helping people to identify those
21:49things that that that work for them.
21:51So that's just a very brief intro
21:53to what actually goes on now.
21:55What I'd like to do is share with
21:57you 2 case examples that hopefully
21:59illustrate that more thoroughly for you
22:01and what the what the outcomes can be.
22:04So of course I've changed him like key
22:06things to protect people's identities,
22:08but everything that I'm sharing
22:09with you really, truly happened.
22:11OK, so yeah,
22:12so the first case I'd like to
22:13share is about somebody they always
22:15called Bob and Bob had a diagnosis
22:17of schizoaffective disorder and he
22:19was not doing well psychiatrically.
22:21He was actually in hospital.
22:22Because he'd attempted suicide.
22:24Recently he was actually in the
22:25hospital fighting with his psychiatrist
22:27about medications.
22:28The psychiatrist was of course
22:29saying if you want to get better
22:31and you'd like to get out of here,
22:33then you're gonna have to take this stuff.
22:35And Bob was saying not really interested.
22:37So there was a whole bunch of
22:39frustration going on and not much else,
22:41but he'd seen a post up in
22:43the hospital for one.
22:44It was a research study providing genetic
22:45counseling in that context and it said,
22:47do you have a diagnosis of schizophrenia,
22:49schizoaffective or bipolar?
22:50Would you like to better understand
22:51why you have your illness?
22:53If so,
22:53give us a call so that's
22:55exactly what he done.
22:56So I was there to meet
22:58with him because of that.
22:59So I like to do my genetic counseling,
23:01not just sort of sitting down
23:03and getting straight into it.
23:04I like to do a little bit of chit chat,
23:07get to know you at the beginning, right?
23:09So I sat down with Bob to do my chit chat,
23:12get to know you and it turns out
23:14that he actually had a graduate
23:15degree in psychiatric genetics,
23:17which I have to.
23:18So we had this complete nerd out session
23:19about where you at the World Congress
23:21on psychiatric genetics and this,
23:23you know you were all wasn't it good,
23:25you know?
23:26Anyway,
23:26so we had this lovely nerd out session,
23:29but what that did to me was basically
23:31make me assume that I knew what his
23:34explanation for cause of illness would be,
23:36and so that's the fundamental question
23:38that you ask in genetic counseling.
23:40No matter what the condition,
23:41can you tell me what you understand
23:43to be the cause of your illness?
23:46And I almost didn't ask him
23:48because of my assumption.
23:49However, reptilian genetic counselor
23:50brain kicked in and I did choke
23:52out my question and his response
23:54absolutely floored me, he said.
23:56Bad life decisions and I was like.
23:59But what we were just talking about
24:01your graduate degree I don't understand.
24:03And he said, Oh no, I understand
24:05that at the level of the population,
24:08genetics is really important.
24:09It's just that I know that in my own case
24:13it was this thing that I did that thing.
24:15The fact that I smoked way too
24:18much pop when I was an adolescent.
24:20That's why I specifically
24:22have this condition.
24:23So another thing that we do in genetic
24:26counseling obviously is take a detailed
24:28three generation family history.
24:29In this case focused on
24:30psychiatric disorders.
24:31So I did that with Bob and of course he
24:34was able to give me all the information,
24:36but he hadn't really sort of considered it.
24:39In light of why he was,
24:40he had the condition that he did so.
24:43Actually both of his parents are affected,
24:45not specifically with schizoaffective,
24:46but with closely related conditions.
24:47So I draw drawing out the family
24:49history and I'm shading people in to
24:51illustrate their affected status,
24:53and I turn my.
24:54You know picture of his family around
24:56and show it to him together with the
24:58jar model that we I just showed you
25:00and he burst into tears and to use his words.
25:03He started talking about how he
25:04felt for the first time like a
25:06weight of guilt is being lifted.
25:08He started to say things like I
25:10can see for the first time that
25:13perhaps it's not all my fault.
25:15Right,
25:15so basically that's why I'm
25:16talking to you today.
25:17'cause he's been living with his
25:20diagnosis for 20 years and it took me an
25:23hour and a half to get to a place that was.
25:26Quite profound for him.
25:27And again I want to show you that
25:30there's no genetic testing here.
25:32We're not talking about pregnancy,
25:33but this is genetic counseling.
25:35But the story doesn't even end
25:37there because he was participating
25:38in this research study we followed
25:41up with people one month later,
25:43and when I did that with him,
25:45he was able to explain to me that
25:47once he understood that there was a
25:50biological contribution to his own illness,
25:52then a biological treatment
25:54started making sense.
25:55So we'd stop fighting with the psychiatrist
25:57about medication he was taking them.
25:58He was out of hospital and he was
26:00doing much better psychiatrically
26:01than he had been in years.
26:04So for me this is this is a.
26:07This is a big one.
26:09We actually designed an entire research
26:11study based on Bob's experience to try
26:13and work out if genetic counseling does.
26:15In fact, if we can quantitatively measure
26:17the change in medication adherence
26:18associated with what we're doing anyway,
26:20I can tell you about that
26:22later if you're interested.
26:23But anyway, for the for the haters and
26:26doubters amongst you who are going, Oh yeah,
26:28well, that's all very well, isn't it?
26:30But you do genetic counseling and he needed
26:33to be convinced that genetics was important,
26:35but what if it was the other way round?
26:38What about if somebody knows it's all just,
26:40you know, thinks it's all genetics,
26:42what then got you?
26:43Don't worry, that's my next case.
26:45So OK, so this one is about somebody
26:48I always like to call Jane.
26:50And Jane had a diagnosis of bipolar disorder
26:53about which she was very out at work.
26:55So everybody knew they were writing
26:57articles about in the company newsletter.
26:59You know, to do self congratulatory
27:01back patting about look,
27:02how good we are at supporting
27:04people with mental illness.
27:06She loved her work and she's
27:08really good at it.
27:09So when she came in my first
27:11impression of her was like,
27:13wow, this is 1 empowered lady.
27:15However, her mental health was not great.
27:17Her physical health was not great.
27:19She was quite overweight.
27:20She had sleep apnea.
27:22And as you can imagine,
27:23with bipolar disorder,
27:24that's not a great combination necessarily,
27:26and so she was having to take
27:27time off the job that she loved
27:29because she was having periods of
27:31like depressione that just really
27:33weren't particularly well managed.
27:35So I told him the fundamental
27:37genetic counseling question tell
27:38me what you understand about your
27:39illness and so she felt her illness
27:41was caused entirely by genetics.
27:42And when I tried pushing like so,
27:43can you know things like can you
27:45tell me what was going on for you?
27:47Do you think there's anything
27:48else and she's like?
27:49No, I know it's just genetics.
27:51That's why I'm here.
27:52So hurry up lady,
27:53let's get on with it.
27:54So I tried a different tack and I
27:56tried asking her can you tell me
27:58what was going on when you first
27:59got sick and she listed a litany
28:01of things that like shouldn't
28:02happen to people in a lifetime,
28:04let alone in the space of six months,
28:05which is really what happened.
28:07Her.
28:07So she was able to say that these
28:10happened around the time she got sick,
28:12but she hadn't really put them
28:14together as having anything to
28:15do with the onset of illness.
28:17If you like so I'm,
28:18you know, did family history.
28:19There's really nothing there,
28:20so I'm, you know,
28:21working with her with the family
28:23history and with the Jar model
28:25pictures that I showed you and I had
28:27to work quite hard to get her to,
28:29you know.
28:29Latch on to the idea that it's not
28:31just genetics and I had to try
28:33a number of different ways,
28:35and when I actually got there the
28:36way I knew I got there was because I
28:39literally watched the blood draining
28:40out the bottom of her face in her eyes.
28:42Kind of going like this,
28:43and when I asked her what was going on,
28:45she said. So you mean to tell me it's
28:48not just genetics and I was like?
28:51She was horrified Becausw she
28:52felt that because she you know
28:54she's already out at work,
28:55but she felt that people would judge
28:57her now like now she understood
28:59that it wasn't just genetics.
29:01She felt she would.
29:02You know people would see it as
29:04being more culpable, basically.
29:05Um, so thing I omitted to tell you
29:08was that she was there because she
29:10was terrified that her daughter was
29:12going to develop bipolar disorder.
29:14In her words, any day now.
29:15So she'd developed bipolar herself at 21.
29:17Her daughter just turned 21,
29:19so in her mind, it was inevitable.
29:23So I worked with a really hard to talk
29:25about how there might be more that,
29:27you know she could do to protect
29:29her own mental health if we accept
29:31that it's not just genetics,
29:32maybe there's more we can do.
29:34Sleep, nutrition,
29:34exercise,
29:35good social support that stuff because
29:37really all she was doing was taking
29:38the psychotropic medication that
29:40had been prescribed by her family
29:41doctor when she was first diagnosed.
29:42She'd never had a psychiatrist,
29:44and I've tried to help her see that,
29:46you know.
29:48You know, if it's not all genetics,
29:50yay means your daughters, not.
29:51It's not a foregone conclusion,
29:53right?
29:55However, I wasn't really
29:56sure she heard any of that,
29:58and then it got even worse.
29:59So I got to.
30:00End of the session and she was
30:02participating in that same research study,
30:04so there was some questionnaires to
30:05complete at the end and we prearranged
30:07that she would do that with one
30:09of the members of my research team
30:10because I had somewhere else to be.
30:12So I thank you for participating.
30:14I told her how nice it was to meet her
30:16and stuff and I had my hand on the door
30:19handle to get out and she said to me,
30:21the other thing is,
30:22if we known it was anything
30:23other than just genetics,
30:25we would have had more children
30:26and she burst into tears.
30:27So I tried to stay and talk to
30:30her about it and she did this.
30:33Again, reason she said anything was
30:34because she knew she didn't wasn't
30:36going to have to talk about it.
30:37Um, so yeah,
30:38you may be wondering why on Earth
30:40you telling us this horrible story
30:42like this isn't a good thing.
30:43Well,
30:44actually kind of is because
30:45within a couple of weeks Jane
30:47had actually changed her GP.
30:48the GP was working with her on ways
30:50to better manage her sleep apnea so
30:52that her sleep wasn't so disrupted
30:54to better manage her mood stuff.
30:56She had a psychiatrist for the first
30:58time who was helping her with trying
31:00a new medication which already seemed
31:02to be perhaps working better for the
31:03higher than the other one had done.
31:05She was taking control of our
31:07own physical and mental health.
31:09So she was working towards
31:11eating and sleeping better,
31:12but most excitingly to me she
31:14signed up for mindfulness meditation
31:17classes together with her daughter.
31:19So and again,
31:20she ended up in a place where her
31:22mental health was much better
31:23than it had been for her in years.
31:25Ended up taking less time off the
31:27job that she loved, blah blah,
31:29blah, blah, blah, right again.
31:30There's no genetic testing.
31:31There's that we're not talking
31:32about pregnancy,
31:33but this is the sort of impact
31:34that that genetic counseling can
31:36have in these environments.
31:37Sorry,
31:37I get so excited about talking
31:39about this stuff.
31:39I've actually gone on for
31:41longer than I intended to,
31:42so I'm gonna try and speed up a bit.
31:44Sorry bout that.
31:45We are going to do a very quick
31:47aside because I want to point out
31:48that if you're paying attention
31:50with both of these two stories,
31:52what you will have no tist.
31:53Is that people change their behavior
31:55right in response to what we did
31:57in terms of the genetic counseling.
31:59Now behavior change to reduce the
32:01risk of common complex conditions
32:02is one of the like Golden grails
32:04of genomic medicine, right?
32:06This was a publication that came out in
32:08The Lancet by Victors Owl a few years ago,
32:11now in which he talks about
32:12how the US health care system
32:14could save 600 billion dollars
32:16or something ridiculous
32:17in the next 50 years.
32:18If we could only help people to
32:21change their behavior to reduce
32:22their risk for heart disease
32:24by telling them how risk they.
32:25Up the risk they were at
32:27based on their genetics.
32:29Now this piece got slammed
32:31for a variety of reasons,
32:32but the point being that that this
32:35that that this is the the idea.
32:37The concept is is potentially real,
32:39that if we could help people to
32:41change their behavior to reduce the
32:43risk for common complex disease
32:45like heart disease like diabetes,
32:47like psychiatric disorders,
32:48there's a potential for
32:50enormous economic benefits.
32:52However,
32:52we know and I'm just flashing up a
32:54bunch of studies here in culminating
32:56with the Cochrane review that
32:58genetic information does not get
33:00people to change their behavior.
33:02It just doesn't work.
33:03So how on Earth am I having the gall to
33:06sit in front of you this morning and say,
33:09hey, our genetic counseling
33:11does though about like how?
33:12How can I?
33:13How can I say that?
33:15Well,
33:15genetic counseling is not the same as
33:18genetic information and to my mind
33:20if we want to help people change
33:22behavior we need to do two things.
33:24We need to embed the genetic
33:26information that we're providing in a
33:28coherent story of etiology that gives
33:30people a sense of control or agency.
33:32So if you imagine saying
33:33to somebody how you have,
33:35you know your your high
33:37genetic risk of diabetes.
33:38So you need to change your behavior
33:40like where's the connection there.
33:42You just you know what people hear is
33:44genetics equals foregone conclusion.
33:46Right,
33:46so we need to marry that with
33:48the piece about like that's what
33:50exactly what the jar model does.
33:52It shows people that although
33:54genetics is a component,
33:55that doesn't mean you're doomed.
33:57There's things you can do about this, right?
33:59So that's giving people that
34:01sense of control or agency,
34:02and then Secondly,
34:03we need to address their emotions that
34:06can act as a barrier to behavior change,
34:08right?
34:08So, for Jane,
34:09that story I just shared with you,
34:11she had to confront all of
34:13that regret around.
34:14Not having had more children.
34:16Right,
34:16she held on so hard to this
34:18idea that her condition was
34:19caused entirely by genetics.
34:20Becausw it meant that she didn't
34:22have to feel that regret,
34:23but it was also acting as a
34:25barrier to her engaging in those
34:26behaviors that were going to protect
34:28a mental health going forward,
34:30right?
34:30So this is not stuff that you can just give
34:33people information and expect it to work,
34:35it doesn't.
34:36So anyway,
34:37that was a very brief aside,
34:39let's get back to the main thrust
34:41of things here,
34:42so psychiatric genetic counseling is
34:44something that hopefully I've illustrated,
34:46is is something that can be applied to
34:48anyone with any psychiatric disorder,
34:50diagnosis and other family members.
34:52It's really all about psychotherapeutic
34:54Lee walking the final line between
34:56helping people see it's not your fault.
34:58You know it's not your fault
35:00even if you smoked
35:01a ton of cannabis, still not your fault,
35:03but there are things that you can do
35:06to better protect your mental health.
35:08Perhaps for the future, right?
35:09So that's a fine line,
35:11but it's walkable and I'm going to share
35:13data with you in a second to demonstrate
35:15that so it's impactful for recipients.
35:17And as you can probably tell,
35:19I kind of love it,
35:21so it's extremely rewarding from the.
35:23From there, it's from the therapists
35:25or clinicians perspective,
35:26so let's talk a little
35:27bit about the outcomes.
35:28Because yes,
35:29I've shared with you some case studies,
35:31but if you're anything like me,
35:33you'll be going like yes,
35:35but anecdotes or not, the data,
35:37so telling how it actually effects outcomes.
35:39Great, let's do that.
35:40So, as you heard at the beginning,
35:42we actually found it the world's
35:44first specialist psychiatric genetic
35:46counseling clinic here in 2012,
35:47and we didn't just pull it out of thin air.
35:50I've actually been studying
35:52whether or not this could be.
35:54Something helpful for people for
35:55God with 20 years at this point,
35:58which is quite terrifying to realize.
36:00But yes,
36:00so anyway we we established this
36:02clinic based on a body of research
36:04data that we generated over the years.
36:07The first thing was you know.
36:09Well,
36:09actually on the first thing we
36:10did was study whether people
36:12interested in genetic counseling
36:14for psychiatric disorders.
36:15They were then we looked at our
36:17existing clinical genetics service to
36:19see whether people were being referred
36:21and that blue one that you can see there.
36:24Basically The upshot of that was.
36:26To say that they're not being referred
36:28to existing general genetics clinics,
36:29we found that in 40 years of service
36:31this program had only seen 288
36:33people with either a personal or
36:35family history of schizophrenia,
36:37which obviously is like saying
36:38we've essentially seen no one.
36:40So yeah, so OK.
36:41So,
36:41given that people are interested
36:43and they're not being referred
36:44to the existing general clinic,
36:46what about if we provide it
36:47on a specialist basic basis?
36:49Can it be helpful?
36:50So what you're looking at here,
36:52top left is just the very first
36:54tiny little pilot study that I did.
36:56Choose one of these things that you
36:58look back on and kind of go on good,
37:01you know,
37:01because it was literally just me provide.
37:03We didn't have any funding like
37:05I was fresh out of grad school.
37:06This was literally just me providing
37:08genetic counseling for people and then going.
37:10How was that?
37:12Nobody had done anything like that before,
37:14and so it was.
37:15It actually got published.
37:17Since then, you'll be delighted to
37:19know we've done some high quality work.
37:22So we did some qualitative work
37:24looking because people said,
37:25well,
37:25what can you really say to people anyway?
37:28You can't tell him anything definitive.
37:30There's so much unknown,
37:32so we studied Clock qualitatively.
37:33How people responded to that and they
37:36completely get it found it really helpful.
37:38Anyway,
37:39we looked at how people
37:40respond to risk estimation
37:42in the context of psychiatric
37:43disorders and fight.
37:45It's all culminated really with
37:46a randomized control trial of
37:48psychiatric genetic counseling for
37:49that for people with schizophrenia,
37:51bipolar and schizoaffective which showed.
37:53But yes, there were.
37:54There were some really important and
37:56meaningful positive outcomes for people,
37:58so that was really the data
37:59that we used as a basis for
38:01establishing our specialist clinic.
38:03It's a provincial service.
38:04We've currently got 1.3 FT.
38:05Es of genetic counselors.
38:07They're embedded within the
38:08general genetics clinic and we
38:10provide service for men and women,
38:11because, again,
38:12people still think that this is
38:14just all for pregnant ladies.
38:15It's not Bob, for example.
38:18For for any personal family history
38:20of any psychiatric disorders and when
38:22I'm doing grand rounds in Vancouver,
38:24I get lots of questions.
38:25Like you know, we play a game like?
38:28What about eating disorders?
38:29Yes, eating disorders.
38:30What about oh CD, yes, OK.
38:32Oh CD,
38:32what about trichotillomania you know so?
38:34So yes we will see any psychiatric
38:36diagnosis and we we we accept self and
38:39health care provider referrals are
38:41appointments tend to be about 1 to 2
38:43hours and we do a one month post appointment.
38:46Follow up with people and typically.
38:48There isn't any genetic testing
38:49that we provide, you know,
38:50unless it looks like somebody's family
38:52history is 22 kewish or something.
38:53In which case,
38:54of course we do.
38:56So we've actually evaluated the outcomes of,
38:58you know,
38:59in the real world clinical kind of setting,
39:01and so this is the very
39:03first publication from.
39:04It's just reporting on the data from
39:06the first year of their clinical
39:08out clinical study essentially,
39:09and this is the sort of high
39:11level what did we find?
39:13So basically we looked at
39:14empowerment and self efficacy,
39:16and we found statistically
39:17significant increases.
39:18But as you all know,
39:19we have a big enough sample size.
39:21You can make any tiny,
39:23useless, meaningless,
39:23different,
39:24statistically significant.
39:24So what I'm more interested in
39:26here is actually the devalues
39:28which relate to effect size like.
39:30Is the difference that you're
39:31making actually meaningful at
39:32the clinical level to anybody,
39:34and an approximation is that
39:36the value of around .5 ISH is
39:38clinically significant?
39:39Actually didn't know that devalues
39:40came as big as one I had to Google it.
39:46So basically an actually in a
39:47more recent studies or devalues
39:48for empowerment or even bigger.
39:50It's, you know, with the larger
39:52sample sizes that we have now,
39:53it's actually 1.2. So yes,
39:56we are making a substantive difference
39:58to empowerment and let's just marry.
40:00That back to what we were just talking
40:02about in terms of behavior change.
40:04If you want people to change their
40:06behavior to protect their health,
40:08they need to be empowered, right?
40:09That's a necessity.
40:10It's a prerequisite. If you like.
40:12And so we're demonstrating that
40:13we're doing that really well.
40:15Essentially, an at the individual level.
40:1686% of people are showing
40:18improvement in schools,
40:19which is also really cool, I think.
40:22We've been because we've got
40:24like outcome assessment built in.
40:25We've been able to study a whole
40:28bunch of different things to see,
40:30like what correlates with with outcomes.
40:32Essentially, we've got no
40:33relationship between patient outcomes,
40:35an age, sex, ethnicity, psych,
40:37diagnosis,
40:37which I think is all really encouraging.
40:39It means it works for everyone.
40:41We've got no difference in terms of
40:44outcomes in for whether people are
40:46self or health care provider referred,
40:48whether it's an individual
40:49or family appointment,
40:51or whether a train near observer is involved,
40:53so.
40:54That's also really reassuring for our
40:56trainees because they get anxious about.
40:58Well if I'm there.
41:00Is that gonna make it look?
41:02No?
41:02It's fine like, yeah,
41:03we've got data to demonstrate that now.
41:06However,
41:06there is a significant relationship
41:08between patient outcomes and
41:10baseline empowerment score.
41:11Which is kind of interesting.
41:13So and I wasn't necessarily
41:15expecting to find that,
41:17so we just published that.
41:19Just can say earlier this year,
41:21but it's 2021 now, right?
41:23So last year it's in the European
41:25Journal of Human Genetics.
41:27I think.
41:28Basically what we're showing is a linear
41:30relationship between baseline empowerment,
41:32score and the degree to which empowerment
41:35increases after genetic counseling.
41:36So people who have lower
41:38scores have greater increases.
41:40OK, which is.
41:41Kind of an interesting observation.
41:44So we've also been looking at
41:46whether genetic counseling
41:47impact treatment adherence.
41:49We've just literally just published
41:51that like at the end of last year,
41:55and so we've got some very
41:57preliminary suggestion that
41:58perhaps genetic counseling might
42:00actually impact mental health,
42:02which is really interesting.
42:03We've got some data showing
42:05that people do report behavior
42:08change after genetic counseling,
42:09so engaging more in self management
42:12strategies and that sort of thing.
42:15And actually that paper's not here.
42:16That's a maca, ET al.
42:18From 2019,
42:19I think we've looked at whether
42:20various aspects of the genetic
42:22counseling session relate to him,
42:23like timing your family history
42:25if we take it on the phone before
42:27somebody comes in to meet with us,
42:29versus we do it at the beginning
42:32of the session. What impacts out?
42:33So basically what we found is
42:35if we do it before the session,
42:37and I've got all sorts of rationale
42:39why or interpretation hypothesis
42:41about why this might be.
42:42But basically, if we do genetic counseling
42:44before we meet with the person for the
42:47actual genetic counseling session.
42:48We get better outcomes for them
42:49than if we do it just with them
42:52at the beginning of the session.
42:53We've studied the type of room in
42:55which the counseling is conducted.
42:56You know, because we embedded within
42:58a clinical genetics Department some
43:00of our interview rooms literally have
43:02beds with stirrups in the corner.
43:04Where is that?
43:04We do have a couple of actually
43:06nice comfy counseling rooms,
43:07and so we were actually able to study.
43:09Do we get any? We don't.
43:10Sadly I was very sad about that.
43:12It would have been nice if we had a
43:14rationale for arguing for nice comfy
43:16counseling rooms, but here you go.
43:18That's the reality of research people.
43:20And then another thing we studied
43:22was because we write.
43:23OK, this is an important point.
43:25Actually,
43:25I think people tend to assume that if
43:27you're going for genetic counseling,
43:29then you're necessarily going to
43:30be provided with risk assessment.
43:32Your chance to have an affected
43:34child is 27.3%,
43:34but in fact genetic counseling should
43:36be a patient centered intervention.
43:38So your your you can offer
43:39people that to people,
43:41but you shouldn't be forcing it on them.
43:43So if they want to know the numbers
43:45absolutely, we can do that.
43:47But if they don't,
43:48maybe we shouldn't be forcing
43:49it down the next.
43:51So we were able to study whether or
43:53whether discussing risk actually
43:54related to patient outcomes,
43:56and I think I've got something to.
43:58And yeah,
43:58I'm going to share with you
44:00briefly what we found here.
44:02So the way that we contract around
44:04risk assessment in genetic counseling
44:05is that when somebody comes in,
44:07we of course ask them what they
44:09want to talk about, right?
44:11And even if that person says I'm
44:13only here 'cause I wanna know
44:14what the chances for my child to
44:17develop the condition I have,
44:18we say great, no problem.
44:20Yeah, we can absolutely talk about that.
44:22But what we found is really helpful
44:24is if we have some sort of shared
44:26understanding about what these numbers mean,
44:28where they come from,
44:29and what we like some framing you know
44:31about what we understand about how
44:33these conditions arise in the 1st place.
44:35Would you know?
44:35Is it OK with you if we talk about
44:37that first and then we can talk
44:39about the numbers in that context,
44:41people will invariably say yes,
44:43so that's what we do.
44:44And then we once we've done that once,
44:46we've had the discussion about etiology.
44:48We say OK,
44:49so they don't talk about numbers now.
44:51And what we found is that it doesn't always.
44:53Match up,
44:54so if somebody starts at the beginning
44:56saying yes they don't come out at the end,
44:58you're saying yes,
44:59this is what we get.
45:00We get people who start out saying
45:02yes and finish saying yes we get
45:04people start saying no and finish
45:06saying no. But some people do a flip
45:08flopping between right? Any guesses?
45:10Or we can't interact coming really.
45:11Any guesses as to which group is going to
45:13have the biggest increases in empowerment
45:15as a result of genetic counseling?
45:17I'll give you a moment to consider.
45:22This one, so it's the people who
45:24initially come in saying yes please.
45:26I want numbers and after discussing etiology,
45:28so you know what actually I'm good, I don't.
45:31I don't need not need numbers,
45:33they have the greatest increases and
45:35empowerment after genetic counseling and I
45:37think that's because they really get it.
45:39They're like OK,
45:39I can see it's not a foregone conclusion.
45:42I can see that there are things
45:44that I can do to not prevent
45:46but to reduce the risk perhaps,
45:48and so they get what you know when
45:50people say I only want to know numbers.
45:53There only articulating what they're
45:54able to articulate what they
45:56really mean when they say I want
45:57numbers is I'm scared I'm scared.
45:58Is there anything I can do about this?
46:00I don't want my child have this thing right,
46:03so we can so we can address all of
46:04that actually without without going to
46:06numbers and and so it's really important,
46:08I think to make sure that you're
46:10addressing people's actual needs.
46:12I'm not going to talk about that.
46:14'cause I am being bergling on and
46:17I really wanna finish so that we
46:19can talk at the end.
46:21So I'm going to briefly touch on this,
46:23consider implications for genetic testing.
46:25So I mentioned at the beginning how
46:27you can already get your polygenic
46:29risk scores for psychiatric disorders
46:31on a direct to consumer basis.
46:33OK,
46:33So what happens is you can get your
46:36genetic raw genetic information from
46:38testing from 23andMe or ancestry.
46:40People like that you can.
46:42Upload it into one of a whole
46:44bunch of different interfaces.
46:46Third party tools which will then
46:48generate for you your polygenic
46:49risk score for all sorts of
46:52conditions including schizophrenia,
46:53depression, bipolar disorder,
46:55Alzheimer's, you name it right.
46:57So yeah, what we're finding is so.
47:00This is data from impute me,
47:02which is an open source nonprofit
47:05tool of this nature, right?
47:07And what they're showing is that
47:09basically the usage of this service
47:11is just basically skyrocketing,
47:13right?
47:13It's it's?
47:14It's really picking up and taking
47:16off and of the conditions that
47:19are most frequently searched,
47:20a whole bunch of them are psychiatric.
47:23Look at that, right?
47:25This is the top set of.
47:28Things that people go there to search for.
47:31So we actually don't know anything at all.
47:34Basically about how people,
47:35why why people do this first of
47:38all and how they react or respond
47:40once they've got this information.
47:42So what you're looking at here
47:44is Larissa Peck,
47:45who's one of my genetic counseling
47:47students in Kennedy Bully,
47:48who's a recent graduate who
47:50have been working with Anne.
47:51This is Lassa focusing in the middle.
47:54He's the person who developed
47:55this impute me website, you know.
47:57Free open source thinking manner
47:59which so yeah.
48:01And what you're looking at here is
48:02the typical way that all of these
48:04different websites will will give you
48:06data about your polygenic risk score.
48:08And so we ask people you know
48:10who were going
48:11to this website, what they understood
48:13about the data that they'd received right?
48:15So, and I don't know if you can see
48:18there we can do a pop quiz at the end
48:20if you like to see who got this one
48:23right or wrong or whatever but but,
48:25but basically we're finding
48:26that people really just don't,
48:28although it is in bigger.
48:29That's good, but what we're
48:31finding is that really, people?
48:32To understand the data that they're getting,
48:35only 35% of them,
48:36and if you think about who's going to this
48:38website and getting polygenic risk scores,
48:40they're going to be people we would think of
48:43as being early adopters really write this.
48:45This is the front of the wave of
48:47people doing this stuff right,
48:49and so if only 35% of them are getting
48:52understanding what they're getting.
48:54That's a bit worrisome, right?
48:56This bit down here is the bit that
48:58causes me concern, however, right.
49:00We actually used a ninja validated instrument
49:03called the impact of Events scale,
49:05and it has established thresholds an
49:07it's it's obviously anchored onto
49:09the genetic test that people had,
49:11but it's got established threat
49:13thresholds for PTSD and what we found
49:15was that people 5% of people who receive
49:18polygenic risk scores scored above
49:20threshold on this validated instrument
49:22full PTSD as a result of receiving their.
49:24Legion risk scores,
49:25which is kind of terrifying if you ask me,
49:28especially once this starts ramping up
49:29and more people are going there, etc.
49:33So anyway,
49:33to summarize,
49:34and that hopefully we can have
49:36some discussion now,
49:37but hopefully I've managed to demonstrate
49:40for you that understanding cause of illness.
49:42It is really important to people
49:44who have psychiatric disorders
49:46but also to their family members.
49:48And genetic counseling is about more.
49:50It's not the same as genetic testing,
49:52and it's not the same as just
49:54providing information or risk
49:56communication when carefully delivered.
49:57It can really result in positive,
50:00meaningful out.
50:00Homes for families and genetic
50:02testing for psychiatric disorders.
50:04No matter whether it's CNV's,
50:06whether it's polygenic, risk scores, etc.
50:08My strong argument is.
50:10Basically,
50:11if we're embarking on any
50:12any initiatives like that,
50:14we should really be ensuring that it's
50:15delivered in the context of evidence
50:17based psychiatric genetic counselling.
50:19Yeah,
50:19I'm going to leave you with a lovely
50:22picture of my team who is actually
50:24the people that do all of this stuff.
50:27Um,
50:27yeah,
50:27so thank you very very much for
50:29your attention and I'd love to
50:32hear what you've got to say to me.
50:34Yeah,
50:34so I'm going to stop by screenshare now
50:37so that we can look at each other, yeah?
50:41You know, it's still fantastic.
50:42Thank you. No problem.
50:44I see some hand clapping as icons.
50:46We can't give you the full applause
50:49that you would deserve if people can
50:51post their questions into the chat box.
50:54Maybe we can organize from there.
50:58Oh, I see the first question.
51:01It's could I explain how empowerment is
51:03measured in any pointers for clinical use?
51:06Yeah, that's a lovely question.
51:07Thank you for asking, because yes,
51:09I omitted to talk about that.
51:11Did my sorry in the studies
51:13that we've been doing.
51:14We've been using a scale called the
51:17genetic Counseling Outcome Scale,
51:18which is a very generic name.
51:20But actually the construct that
51:21it measures is empowerment.
51:23So the reason that we so there are
51:25of course there are other validated
51:27instruments that measure empowerment.
51:29But the reason that we chose that one is
51:31because it was specifically developed.
51:33For use in clinical genetic settings
51:35and validated in that context as
51:38well so interesting that you should
51:40ask about pointers for clinical use.
51:43Be 'cause we're actually looking
51:46at the moment at.
51:48We've been doing some some rash
51:51measurement theory stuff with the
51:53scale and what we're trying to do
51:55with it is to develop it into an
51:57instrument that could be used,
51:59for example by psychiatrists,
52:01to identify people who might benefit
52:02most from psychiatric genetic counseling.
52:04Because as I mentioned,
52:06we demonstrated that people who
52:07scored lower on empowerment with
52:09the people who benefited most from
52:11psychiatric genetic counseling.
52:13So yeah,
52:13we're working on developing a
52:15really brief instrument that might
52:17be able to be used.
52:19Um, to identify you by by clinicians.
52:21People like yourselves to
52:23identify people that might benefit
52:24from what we have to offer.
52:28Jenny looks like Chris Pittenger has
52:30a question. Chris Evan if you knew.
52:33Yeah thanks, thanks for that really
52:35great talk in a wonderful perspective
52:37on how to address these issues with
52:39patients. I know there's been some
52:41discussion I'm most familiar with it in the
52:44bipolar literature, but it comes up in some
52:46other diagnosis as well.
52:48Where genetic risk factors may also
52:50provide some benefit. So there's
52:51been discussion about how risk for
52:53bipolar may correlate with creativity.
52:55There's been some discussion how
52:56risk with OC D might correlate with
52:58adaptive organizational traits in
53:00modest doses, so I'm just curious
53:02how you address that complexity.
53:04In your counseling to summarize
53:05how we address that in one word,
53:07we would say I'd say carefully.
53:11But but yeah, to give you a
53:14little bit more context so so.
53:16Yeah, we absolutely do,
53:17and so you know the language that I've
53:20been using with you today is around genetic
53:22vulnerability or genetic susceptibility.
53:25Or you know predisposition if you like.
53:27And those words have varying degrees of
53:30negative connotation attached to them, right?
53:32So another way of talking about it
53:36would actually be to talk about.
53:38Plasticity, if you like which is you know,
53:41so you know.
53:42And I I think for me the word predisposition
53:44is the least negative of all you know
53:47of the susceptibility vulnerability,
53:50kind of group of wording.
53:51So, so the way that we often talk
53:54about that in the context of genetic
53:57counseling would be to have you
54:00seen the orchid dandelion stuff.
54:03Yeah OK cool yeah.
54:04So for those of you that don't
54:06know it the so it's about.
54:08It's about plasticity and
54:09it's about exactly this stuff.
54:10It's about how there is evidence
54:12that the genetic factors that
54:14contribute to vulnerability for these
54:16conditions also can confer some
54:18traits that we tend to think of in a
54:20more positive light creativity blog.
54:21You know,
54:22all of those things we were
54:23just talking about.
54:24So the concept is that there are,
54:27you know, people can be thought of
54:29as orchids or dandy Lions, right?
54:30Dandy Lions are really robust,
54:32they can grow through cracks in paving slabs.
54:35Their environment doesn't matter
54:36so much to them.
54:38They will produce a dandy lion flower, right?
54:41Whereas on the other hand,
54:43orchids are not going to go
54:45through cracks in pavements.
54:46They're just not.
54:47However,
54:48with the right circumstances and environment,
54:50or kids can thrive, and they can.
54:53Arguably, depending on your perspective,
54:55produce a flower that is more
54:57beautiful than Dandy lion.
54:58Not that this is a competition,
55:00of course,
55:01so so it's a way of helping people to see.
55:05That you're not doomed that there,
55:07but there are positives,
55:08so there can be positives associated
55:10with some of this.
55:11However,
55:12there's it can be really difficult to
55:14have this conversation with parents,
55:15for example, who then get like.
55:17OK,
55:18I'm going to do everything within my power,
55:20you know.
55:21And so we you need to be really
55:23careful about tempering that with.
55:25We don't know what that perfect
55:27environment necessarily looked like.
55:29And we don't have complete control
55:31over the environment either, so.
55:32You know so,
55:33so so I wasn't being facetious when
55:36I said we handle it carefully because
55:38we really do have to handle it carefully,
55:41but I think it's a beautiful
55:43and important concept.
55:44So thank you
55:45for asking about it.
55:47Yeah, yeah, thank you.
55:48Chat one of them is is
55:50actually pretty close to that.
55:51So asking whether you see you
55:53ever see people adopt extreme
55:55behavioral changes afterwards,
55:56such as extreme exercise. Oh,
55:58that's a lovely question because
55:59especially if we're thinking about
56:01things like eating disorders.
56:02Of course, this gets really important.
56:04So in all of this we we have to be
56:07like you have to be super aware of
56:10exactly what you're dealing with, right?
56:12So we have to be very careful about
56:15ensuring that you know it's about.
56:17In these contexts about moderation.
56:19And no, actually we have to our knowledge.
56:21So far we haven't seen extreme examples
56:24or of that kind of thing but but
56:26we do try to be very mindful about
56:29ensuring you know we talk to people,
56:31for example about self compassion.
56:33You know this idea that like.
56:35And once you're telling people that hey
56:37sleep diet and exercise blah blah blah,
56:39you know. So people,
56:40I imagine at least that people can
56:42get into a place where they do.
56:43Oh my God, I had fries for lunch
56:45and then pizza for dinner.
56:47And I know that I should do better and they
56:49do self flagellation with guilt stick.
56:51So we talk to people about exactly that.
56:53We took you.
56:53This is not about perfection.
56:54This is not like what even is that
56:56it's not a thing.
56:57It doesn't exist, stop it.
57:00So what we're aiming for is
57:02doing the best you can,
57:04and being kind to yourself
57:05if that's just not possible,
57:07right?
57:07Yeah, that sort of thing, not a question.
57:09Have you looked at individual
57:11differences in response to the
57:12genetic counseling sessions in
57:14ultimate treatment outcomes?
57:15And if you've seen any effect in
57:17addiction prevention and or treatment,
57:18right? Thank you.
57:19Yeah, great question.
57:20So yeah, we have looked at in the
57:22Gerard paper from the end of last
57:24year that I mentioned briefly,
57:26we did look at like different diagnosis
57:28and I think substance use conditions
57:30with one of them that we separated out.
57:33And when we're not seeing any,
57:35there's no like there's no statistically
57:38significant differences in outcomes between.
57:41You know people based on diagnosis.
57:42We've also looked just recently.
57:44I've had a student won an award
57:46actually for a study where she was
57:48looking at Big 5 personality traits and
57:50coping styles in relation to outcomes
57:52of psychiatric genetic counseling.
57:53And Interestingly,
57:54she found that there was no,
57:55there was no difference between the groups.
57:58But I have theories about why that
57:59might be so because I've said right
58:01psychiatric genetic counseling
58:02is very patient centered,
58:04so I think that what we could be doing
58:06is actually just modifying what we're
58:08doing to meet the individual patients needs,
58:10which is why we don't
58:12really see a difference.
58:13Possibly I don't know.
58:14It's an interesting idea anyway.
58:16So yeah, we are.
58:17We're very interested in exactly
58:18those questions,
58:19and studying them actively.
58:22Awesome and a question relating
58:24to monotonicity versus polygenic
58:26city and and whether you can,
58:27clinicians are ready to help people
58:30with PRS information that's coming
58:32from direct consumer is that the end
58:34of that answer?
58:39Might not be much more to the question.
58:42It's a great question and and it's actually,
58:45you know, that's why I wanted to
58:46include it in my presentation today
58:48because I think many clinicians aren't
58:50even aware that this is happening yet.
58:53But we are at the front that we're
58:55at the leading edge of the wave.
58:57It's coming, so I would say that
58:59should you should you get a patient
59:01coming in with this stuff and you
59:03feel unsure about how to handle it,
59:05please reach out to your genetic counselor.
59:07Colleagues were here to help y'all.
59:09Based in the US,
59:11and there's actually a tool called
59:13Find a geneticcounselor.com where
59:15you can literally find genetic
59:16counselors in your local area who could
59:18help you with this sort of thing.
59:20If it was a concern, yeah.
59:23We may
59:24find them, but I don't think they're
59:25going to be as cool as you are.
59:28Play some pretty cool ones. I have to
59:30say to me it looks like we've
59:32gotten to the end of the questions
59:34and we're at the one hour mark.
59:36So so I think maybe that is a good
59:39moment to pause and again say.
59:41Thank you so much for joining us.
59:43What a fantastic presentation.
59:45Thank you. Yeah, no problem is very
59:48nice to meet. You all have a good day, yeah?