Yale Psychiatry Grand Rounds: September 30, 2022

September 30, 2022

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"A Celebration of the Life and Work of Steven M. Southwick, MD"

Speakers: John Krystal, MD; Dennis Charney, MD; Robert Pietrzak, PhD; and Janitza Montalvo-Ortiz, PhD

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00:00Honor the life.
00:04To honor the life and work
00:05of Doctor Steven Southwick,
00:07my name is Robert Peter Zack.
00:08I'm one of Steves mentees,
00:10a professor in the department,
00:11and I've had the privilege of knowing and
00:14working with Steve for 15 wonderful years.
00:16Steve was more than a mentor to me.
00:18He was the 2nd father,
00:19one of my biggest supporters,
00:21and dearest friend and colleague.
00:23We are joined today by several
00:25of Steve's family members,
00:26including his wife Bernadette,
00:27as well as many of his friends,
00:29colleagues, and mentees.
00:30I'm going to begin today with a
00:32brief review of Steve's life and.
00:34Academic work and we will then
00:36have three separate presentations
00:38from doctors Crystal Charney,
00:39Montalbo, Ortiz, and me.
00:45Steve was born on April 24th,
00:481948 in Boston, MA.
00:49Here's a picture of Steve
00:51as a child sitting on his
00:52father's lap with his family.
00:56Steve's family showed a clear
00:58commitment to service and education.
00:59His father, doctor Wayne Southwick,
01:01was the founding chair of orthopedic
01:04surgery at Yale and a gifted sculptor.
01:06His mother, Jesse Ann Southwick,
01:08helped organize the Fellowship,
01:10Place a supportive community to help
01:12promote mental health in New Haven,
01:14and actively supported the Connecticut
01:16Hospice and Old Lyme Art Academy.
01:19Steve, Sister Marsha was a creative
01:21writing professor, now retired,
01:22and his brother Frederick is a highly
01:25accomplished infectious disease.
01:26Position and professor at
01:28the University of Florida.
01:31During the Vietnam War,
01:32Steve served in the US Army
01:34and was stationed in Germany.
01:35After his service,
01:36he attended Yale,
01:37graduating in 1974 with a
01:40degree in psychology.
01:41Here's a picture of him playing football.
01:43He liked to joke that this was one of his
01:46earliest experiments and stress inoculation.
01:49He then attended medical school at
01:51George Washington University and
01:53completed his psychiatry residency at Yale.
01:56Steve then remained at
01:58Yale throughout his career,
01:59where he forged rich collaborations
02:01and decades long friendships.
02:03He was beloved by his friends and
02:05colleagues and mentored hundreds
02:06of trainees at all levels.
02:08Here are some pictures from Steve's
02:10inauguration as the Greenberg endowed
02:12professor giving a keynote address,
02:14and with his longtime colleague Andy Morgan.
02:19Here's one of my favorite pictures of Steve.
02:21I remember how proud he was to
02:23have organized his desk thanks
02:25to this large green garbage bin.
02:28And here is Stephen Action,
02:29reading and revising papers four at a time.
02:33I think the one with the most
02:35extensive editing is mine.
02:38On a more personal note,
02:39Steve was a loving family man.
02:41Here are some pictures
02:42of him with Bernadette,
02:43his daughter and son-in-law,
02:45with his grandchildren,
02:47and from his wedding day.
02:51Our dear colleague and friend
02:53Steve passed away on April 20th,
02:552022 at the age of 73,
02:58just four days shy of his 74th birthday,
03:01after a courageous 5 year battle
03:03with metastatic prostate cancer.
03:05At the time of his death,
03:07Steve was the Glen H Greenberg
03:09professor emeritus of psychiatry,
03:10PTSD and resilience at Yale and
03:13Medical Director emeritus of the
03:15Clinical Neuroscience division of
03:17the VA National Center for PTSD.
03:19There is no question as to Steve's impact.
03:22On the field of psychiatry,
03:24with over 400 published papers,
03:26books and chapters focused on
03:28understanding PTSD and resilience,
03:30he has received numerous awards
03:32for his research, teaching,
03:34mentorship and clinical work.
03:36His published work has been
03:38cited more than 62,000 times,
03:39and he has been recognized as among the
03:42most highly cited researchers by Thompson,
03:45ISIL.
03:45But more than that,
03:47Steve practiced what he preached
03:49and embodied and lived the
03:51resilience factors that he studied
03:53and that we will hear about today.
03:55Steve came into this world and
03:57changed our lives for the better.
04:00His kindness, compassion,
04:01love,
04:01and sense of humor touched all
04:03of us who knew him.
04:05In her eulogy and prayer of Thanksgiving
04:07at Steve's memorial service,
04:09the Reverend Shelley Emery
04:10Holness described him as a man
04:12of great faith and integrity who
04:14felt compelled to help veterans,
04:16especially Vietnam Veterans who
04:18did not return home to accolades
04:21of thanks for their service.
04:23She further noted that Steve brought
04:25light to the cracks in those he served.
04:30The presentations you will hear today,
04:32we will review the incredible
04:34breadth and depth of Steve's work.
04:35I would like to now introduce our
04:37first presenter, Doctor John Crystal.
04:39John, of course,
04:40does not need an introduction to this group,
04:43but I'll say that he has known,
04:44trained with and worked with
04:46Steve for nearly 40 years,
04:47beginning from being a resident under
04:50Steve to eventually becoming his boss.
04:52Together they have done some of
04:54the earliest and most pioneering
04:56studies on the neurobiology and
04:58pharmacological treatment of PTSD,
05:00which we will hear about today.
05:02John?
05:04Thank you, rob. And and it's wonderful
05:07to be with all of you to celebrate the
05:10life and career of Steve Southwick.
05:13I think we can all say that.
05:16That, Steve, was one of the most
05:19unique people that we ever met
05:22and someone who we anyone who
05:24who came into contact with them.
05:27Was better off for that contact,
05:29I I also wanted to acknowledge.
05:32That special to have Bernadette here
05:35with us and and to be presenting
05:38with Rob and Dennis is, is great.
05:40It's great to have the the
05:43old team back together.
05:45So I'm going to be talking about
05:47about the start of Steve's kind
05:50of neurobiology work and how his.
05:54Um, contributions to PTSD research really
05:59helped to begin the modern neuroscience
06:01of post traumatic stress disorder.
06:04You saw pictures already
06:06of Steve's early life.
06:07This is a picture that Bernadette
06:10shared from Steve's days at at Hopkins,
06:13the local high school.
06:15Here's a picture from the 1980s.
06:18Where, uh, where, uh,
06:20the very beginning of the work
06:23on PTSD was taking place.
06:25And here is Rachel Yehuda,
06:28who was with us at the VA Earl Giller,
06:30a former chief of psychiatry at the
06:33VA and and and Steve in the 1980s.
06:36Here we are, Steve, Dennis and I in Moscow.
06:41And this was late, Gorbachev.
06:46The uh,
06:47uh.
06:47This was after the terrible
06:50crisis in Chernobyl and also the
06:53Soviet invasion of Afghanistan.
06:56And this was one of the more
07:00extraordinary adventures that the
07:02three of us had the good fortune
07:04to share to to to be talking about
07:08PTSD with people in that context.
07:11So.
07:12What was PTSD like before Steve Southwick?
07:17Here's a review paper from the
07:20early 1980s which summarized the
07:23state-of-the-art at the time.
07:25Which was that there was evidence
07:29of hyperactivity of the autonomic,
07:32or sympathetic nervous system that was
07:35increased by exposure to trauma reminders.
07:39And that there were elevated 24
07:43hour urine levels of norepinephrine.
07:47In people with PTSD,
07:49and that this relative increase in our
07:52predefine was greater than the levels of
07:56cortisol that one might have expected,
07:59and that animal models suggested this
08:02regulation and conditioned activation
08:04of the noradrenergic system based
08:06in the locusts release in the brain
08:09and providing noradrenergic input
08:12to the higher centers of the brain.
08:16So there had been some general ideas.
08:20About that PTSD had a neurobiology,
08:26but actually at that time the idea
08:29that there was a biological component
08:32to PTSD was still hotly debated,
08:35and in fact some people felt that
08:38PTSD shouldn't even be studied
08:40from a biological perspective,
08:42given the the interpersonal nature of a
08:47lot of the trauma that people experience.
08:51But how could we study the
08:54neurobiology of PTSD?
08:56The the tool that we initially stumbled
08:59on came from the work of of Dennis and
09:03his collaborators in the early 1980s,
09:06Alan Breyer,
09:08George Henninger.
09:09Which was the idea to probe.
09:13To probe the integrity of a particular
09:17neural signaling mechanism by giving a drug
09:20that would stimulate a specific target
09:22in the brain and then measuring outcomes,
09:25behavioral and biological,
09:27that could end index or provide a measure
09:30of the sensitivity of that signaling
09:33mechanism in the brain and body.
09:36So for the case of trying to
09:38understand noradrenergic systems that
09:41had been implicated by the animal
09:44models and sympathetic arousal.
09:46Doctor Charney developed a technique
09:48of giving a drug that blocked feedback
09:51inhibition via blocking the Alfred
09:54to noradrenergic receptor and then
09:57measuring the behavioral responses.
09:59And you can see that this approach
10:02produces very little response in terms
10:05of changes in anxiety and healthy
10:08subjects and of limited span of.
10:11Increases in a metabolite of
10:13neuropil nepheline called MHB G,
10:16which can be measured in the blood.
10:19But when he gave the same drug
10:21to patients with panic disorder,
10:22he got much bigger increases in anxiety
10:26and much bigger increases in MHG,
10:29in other words,
10:31indicative of a greater norepinephrine
10:34response associated with the
10:37symptoms of of panic disorder.
10:39This was a sign that the
10:41feedback inhibition mechanism,
10:42the A2 adrenergic receptor,
10:46was.
10:47Functioning in a deficient way
10:49in panic disorder,
10:50and this was in some ways one of the
10:53first specific mechanism a signaling
10:56mechanisms identified as contributing
10:58to the biology of panic disorder.
11:01When Steve and I just to
11:04illustrate this idea graphically,
11:07normally when the norepinephrine
11:08neurons are activated,
11:10you get a little bit of norepinephrine
11:12release and and that's because
11:15when norepinephrine is released
11:16by neighboring neurons,
11:18it shuts shuts down the norepinephrine
11:21neurons via the A2 adrenergic receptor.
11:24In panic disorder,
11:26when you get the same degree of
11:29neural activation because the A2
11:31receptors are less functional,
11:33you get much bigger norepinephrine releases.
11:37And one consequence which I'm going
11:40to come back to in a little bit is a
11:43down regulation of the postsynaptic
11:46response to norepinephrine overtime
11:48via the beta adrenergic receptor.
11:52So.
11:52Steve and Dennis and I conducted
11:56this first study trying to identify
11:59a neural signaling mechanism in
12:02post traumatic stress disorder.
12:05And we did this by giving yohimbine.
12:08And showing that there was,
12:10for the first time,
12:12an increase in PTSD symptoms severity
12:16that could be attributed to a
12:19manipulation of a specific neural mechanism.
12:22Also,
12:22that this increase in PTSD symptoms was
12:27associated with a greater increase in in MHG,
12:31meaning a greater activation
12:34of norepinephrine,
12:35meaning that this mechanism,
12:37the A2 noradrenergic inhibition
12:40of norepinephrine neurons,
12:42was deficient in PTSD.
12:46This work was followed by a study led
12:48by Doug Bremner, who was with the
12:51National Center for PTSD at the time.
12:54And he gave he did the same study,
12:57giving yohimbine to healthy
12:59people and people with PTSD.
13:03And measuring brain activity,
13:05this time using positron emission
13:08tomography to measure cortical metabolism.
13:12And what Doug showed was that when
13:14you give yohimbine to people,
13:16you activate prefrontal cortical metabolism.
13:20However, when you give.
13:23Yohimbine to people with PTSD,
13:26you don't produce the same degree
13:29of prefrontal cortical metabolism,
13:30and this was a sign that
13:33the postsynaptic response.
13:35In other words,
13:36the response to norepinephrine
13:37by neurons by cells in the
13:40prefrontal cortex was also blunted.
13:42So both the presynaptic inhibition
13:44feedback inhibition of the
13:47norepinephrine neurons was deficient,
13:49as well as the postsynaptic
13:51reactivity to norepinephrine.
13:55One of the most striking things
13:58about this study that Steve LED.
14:01Was the experience that people
14:04participating in this study.
14:06Had when they received yohimbine.
14:09And so Steve and I would would
14:13sit with the patients and record
14:16aspects of of the sessions and
14:19and and and what we saw was that.
14:23For the first time that we could bring on
14:29symptoms of dissociation and flashbacks
14:32and intrusive memories in people
14:34with post traumatic stress disorder.
14:37In this case,
14:38a veteran with PTSD who is getting yohimbine,
14:41who then has a flashback to a scene
14:44from his combat exposure where he not
14:46only sees a helicopter going down,
14:49he can hear it and he can smell it.
14:52And this was really a powerful message
14:56about the link between the biology
14:59of PTSD and the symptoms of PTSD and
15:04help to stimulate further research.
15:06Trying to understand the the neural
15:10contributions to the symptoms of PTSD.
15:12This work also led to the testing
15:14of a number of treatments for PTSD,
15:17including PRAZOSIN.
15:20And desipramine,
15:21which is a study here led by Esmini Petrakis,
15:25which was one of the first to show
15:27evidence of efficacy of desipramine as a
15:30treatment for post traumatic stress disorder.
15:33So.
15:35That is really the the,
15:37the kind of the first generation
15:40of research that was done
15:42here and and as you can see.
15:47There was a we were.
15:49Really striking new ground.
15:53Steve was leading studies that that
15:57really put PTSD on the map from the
16:01perspective of neurobiological research.
16:03Um, and So what I thought I
16:06would do in the in the next two
16:09minutes or so is just highlight.
16:12How far some of this work has come in the
16:14effort to understand the biology of PTSD?
16:17First in the effort to map circuits
16:21involved in PTSD and and to link
16:24them potentially to deep brain or
16:27other innovative treatments for PTSD.
16:31So in this regard,
16:33I want to highlight the work of Al
16:36Qaeda in the Department of Psychiatry
16:37and Yemi Dami saw in the Department
16:40of Neurosurgery who are conducting
16:41a study involving Intracortical
16:44recording of brain activity in
16:47epilepsy patients prior to epilepsy
16:50surgery in order to map the circuitry
16:54of fear and fear regulation.
16:56And so in this work,
16:59people are playing a video game that
17:02little bit like the game asteroids,
17:05where they're sometimes evading.
17:08Crashing into the asteroid and
17:11sometimes they crash and so we can look
17:14at the neural activity as they are
17:17actively avoiding crashing but also
17:19anticipating a crash and and where
17:22we can look at that fear response.
17:28One of the elegant parts of this
17:30work is that AL is an expert in
17:34computational modeling, and so we can.
17:38Very elegantly mapped the pattern of
17:41behavior across trials as we study
17:44the acquisition of the anticipatory
17:47fear of crashing during these trials.
17:53And because we're recording from
17:55electrodes that are placed in the brain
17:58as part of the neurosurgical evaluation,
18:01we can get a unique window into
18:04the neural circuitry and neural
18:06mechanisms of fear and fear regulation,
18:09which we can then use to inform the
18:12development of brain stimulation treatments
18:15aimed at helping people to regulate
18:19these circuits in a more adaptive way.
18:22A second new area of exploration
18:25has to do with molecular biology.
18:28We've long known,
18:29and this is a quote from Linus Pauling,
18:31the Nobel laureate from 1952.
18:35That someday we'll have a a understand
18:38the molecular basis of our diseases,
18:41and then in the process discover why certain
18:45molecules are effective as treatments.
18:48And the identification of molecular
18:50targets in PTSD research in some ways
18:54begins with a pet study conducted or
18:57spec study conducted here at Yale,
19:00also led by Doug Bremner,
19:02in which Steve and Dennis were collaborators,
19:06which identified a change in in
19:08the binding of a particular ligand
19:12in Vivo 2 receptors in the brain.
19:14This is a GABA a receptor.
19:18Now for the first time we have the
19:21ability of studying in a deep way in
19:24postmortem tissue the actual molecular
19:27signatures of post traumatic stress disorder,
19:30the actual molecular pathology of the
19:33disorder and the first well powered
19:37study led by the late Ron Duman and
19:40and and conducted by Matt Girgenti,
19:43a faculty member now in our
19:46department provided some of the 1st.
19:48And profoundly interesting molecular
19:50insights into the biology of PTSD.
19:54Where we can look across the entire genome
19:57and look at the levels of expression
20:00of the individual genes and identify
20:03many changes associated with PTSD.
20:06I'm just going to mention 21A change in a
20:12molecules expressed by Gabba nerve cells.
20:15In other words,
20:16a signature related to the earlier
20:19pet study whose biology we couldn't
20:22possibly understand in detail.
20:24At that time,
20:25and another interesting and exciting
20:28area was pathology in a group
20:31of cells called microglia that
20:33regulate inflammation in the brain.
20:36Unlike depression,
20:37which is associated with immunologic
20:40activation,
20:41PTSD seems to be associated
20:44with suppression of the of the
20:47genes associated with microglia.
20:50Another profound insight to
20:52emerge from this work,
20:53and this is the last neurobiological
20:56finding that I'll share,
20:58is that PTSD and major depression?
21:01Do have limited,
21:03very limited areas of
21:05overlap in their biology.
21:08But.
21:08They are profoundly different or
21:11disorders from the perspective
21:14of their molecular fingerprints.
21:17This is really a profound idea for
21:19us as all of the treatments that
21:22we have for PTSD were developed
21:24initially as treatments for major
21:27depression and then adapted for PTSD,
21:30and it highlights how important
21:32it is to characterize.
21:34You need the unique pathology
21:36of PTSD if we hope to develop
21:38treatments that are more effective.
21:41For helping people be resilient
21:43and recover from the impact
21:45of their life traumas.
21:47All of this legacy builds from the first
21:51profound insight from Steve Studies,
21:54which is that there are
21:56is a knowable biology of
21:58PTSD and that the symptoms of PTSD
22:02are related to this biology. So.
22:05In some ways, today we both celebrate
22:09and mourn the end of the beginning of the
22:13field of PTSD neurobiological research.
22:16Steve Southwick, a beloved and
22:19respected pioneer, is sorely missed.
22:22He identified the first signalling
22:25mechanism altered in PTSD and influenced
22:27the development of treatments for PTSD.
22:31He helped foster a more mature
22:34understanding of the biology of PTSD,
22:36which is emerging from this bleeding
22:40edge of neuroscience research.
22:42Their PTSD is not simply depression.
22:46And it's enormously it's biology
22:48is enormously more complex than
22:51we ever could have predicted.
22:53We acknowledge our loss.
22:55And thank Steve as he cared
22:58for countless patients,
23:00mentored the next generations
23:02of clinician researchers.
23:03And his the legacy of his research
23:06lives on with us. And those.
23:10Stimulated by his research contribution.
23:13So I'll stop there. And and.
23:17We can move on.
23:18Thanks.
23:19Thank you, John, for such a wonderful
23:21overview of Steve's early work.
23:22Truly groundbreaking and setting the
23:25foundation for where the field is today.
23:27It's my honor to now introduce our
23:30second presenter, Dr Dennis Charney.
23:32Dr Charney is a world renowned expert
23:34in the neurobiology and treatment
23:36of mood and anxiety disorders.
23:38Dr Charney began his career at Yale
23:41in 1981 or within nine years he rose
23:43to tenured professor of Psychiatry.
23:45He then remained.
23:47Deal for a decade before being recruited
23:49to lead the NIMH mood and anxiety
23:52disorder research program in 2004,
23:54Doctor Charney was recruited to Mount
23:56Sinai as Dean of research and is
23:58currently the Anne and Joel Aaron Krantz,
24:00Dean of the Icon School of Medicine at
24:02Mount Sinai and president for academic
24:05affairs for the Mount Sinai Health System.
24:07Doctor Charney has known Steve
24:09for more than 40 years,
24:10and together they have co-authored
24:12more than 100 papers as well as two
24:15of the leading books on resilience.
24:17Today,
24:18we will hear about their groundbreaking
24:19work on the science of resilience.
24:21Dennis,
24:21we're delighted to have you here today,
24:23and thank you for joining us to honor Steve.
24:27Thank you, Rob,
24:28and it's it's a pleasure to be here.
24:31Maybe that's not the right word.
24:33Steve and I, as you mentioned,
24:36Rob, you know, we were friends
24:38and colleagues for 40 years.
24:42We kept in contact, constant contact.
24:47Every week talked every week
24:50as friends and and colleagues.
24:52So I want to talk a little bit about
24:55Steve the scientist and I will touch
24:57on our work it and resilience and also
25:00Steve as a as a friend and a person,
25:04so as colleagues.
25:07John and I, little history here for
25:09those of you who may not know the
25:11history but you know John and I were
25:14at the clinical neuroscience unit.
25:16At CMHC.
25:17And then, you know,
25:18we decided to move over to the VA.
25:21And that that happened around
25:25198087 or so and we changed what the VA
25:29was like at that time to make it more
25:33scientifically based to affect I would say
25:36more evident evidence based treatments.
25:40And and Steve was there and personally
25:43when we went, John and I and some
25:45others when we went to the VA,
25:47Steve had been there for a couple of years.
25:50And I must admit,
25:52I didn't know hardly anything about PTSD.
25:55Steve was in the military.
25:57I knew a lot about veterans,
25:59knew a lot about war.
26:00I was Vietnam era, you know,
26:03which means I did not go to Vietnam.
26:06I I got deferments from going into the
26:09military because at that time I was in
26:12college and then I was in Med school.
26:14That's another story why people who
26:16are in college don't go to war as
26:18opposed to if you're if you're not,
26:20you get drafted.
26:21But actually,
26:22I didn't know much about PTSD or veterans.
26:25And so we we go to the VA.
26:28And Steve taught me.
26:29He taught me a lot about PTSD
26:32as a as a clinical phenomenon.
26:35You know what what it meant to come
26:37back from Vietnam and not be welcomed,
26:39and how serious PTSD was as a as an illness.
26:44So I really was a student of Steve's
26:47in terms of understanding PTSD.
26:51And I and I became fascinated by PTSD.
26:54I've been doing mainly work,
26:56as John mentioned in depression
26:57and and panic disorder.
26:59And I saw understanding PTSD biologically
27:03could really help understanding the
27:05disease and developing new treatments.
27:08So Steve and I and John you know,
27:10we we became partners in that adventure
27:13and Andy Morgan and and Rasmussen and
27:16others got you know, got involved and.
27:20I hope a lot of you experience this.
27:22It was fun, you know, to do the work.
27:25You know we would.
27:27At 5:00 or 6:00 o'clock at night,
27:28we would all get together and and
27:31talk about what we're learning a new
27:34studies that we we crafted it was.
27:38It was just great.
27:41And working with Steve and John and others,
27:43it was, yeah, it was just so much fun.
27:45And and so we started conducting the
27:47studies that John reviewed with you.
27:49That gave us a lot of insight into
27:52what might be what stress does
27:53to the brain and and the body.
27:56It it was really a new field that,
27:59you know, almost every couple of
28:00weeks we learned something new.
28:01It was just,
28:02you know, fantastic.
28:03And also, you know,
28:05other things started to happen.
28:06Andy Morgan you know,
28:08got involved and he he had
28:10connections you know,
28:12with the military and and we did a study,
28:14Steve I and Andy John was involved
28:18where we we studied veterans
28:20actually active duty military who
28:23were involved in active training and
28:26these were mainly special forces.
28:29They were in their seer course
28:32called Survival, Evasion, resistance.
28:34Escape a very serious training exercise.
28:38Andy connected us and what we
28:41found under the very
28:43significant stress of a training exercise
28:47that we characterize the biologic
28:50neuroendocrine responses to stress.
28:53And how it might even relate
28:56to resilience to stress.
28:57And one of the things we we found,
28:59norepinephrine,
29:00obviously was involved cortisol ACTH,
29:04and also neuropeptide Y,
29:06which is a naturally occurring neuropeptide
29:10that has anxiolytic properties.
29:14And so you know that was you know a
29:17real eye opener to study in a sense
29:20normal stress and related to resilience.
29:23Ultimately down years later with with
29:26Steve was very involved in this too.
29:29We made neuropeptide Y and we began to
29:32study it as a treatment for PTSD and
29:35we're still involved in that work and
29:38it started with the work with Andy and
29:41Steve and John with that CPR course.
29:45At some point in the 1990s.
29:50Stephen, I thought, you know,
29:51maybe we could learn.
29:53A lot more about PTSD and maybe
29:56come up with new treatments if
29:59we learned about resilience.
30:01And so we started studies
30:04and resilience that lasted.
30:06Up till the day Steve died that we
30:10ended up studying hundreds of people,
30:13interviewed them.
30:16To learn about resilience and as Steve
30:18and I would say and Steve would say,
30:20we started with a blank slate.
30:22We,
30:22we did not know what characterized
30:26resilient people who who faced very
30:29significant stress and in some cases
30:33experience post traumatic growth.
30:35Didn't develop depression or PTSD,
30:38or if they did,
30:39they were able to deal with it and recover.
30:43And so we studied POW's from Vietnam.
30:47People who had to face natural disasters,
30:52congenital disease,
30:54studied every socioeconomic group
30:58you could think of, and so it was a.
31:01It it was an amazing experience,
31:03you know,
31:04Steve and I and others doing that together.
31:07We studied the POW's when I was
31:09at NIH and Steve would fly down,
31:13stay with me,
31:14and we would interview the the
31:16POW from Vietnam.
31:18We interviewed about 40 of them.
31:20John McCain is the most famous,
31:21but there are many others who
31:23did very well in life,
31:25despite being held in prison
31:27for six 7-8 years,
31:29heavily tortured solitary confinement.
31:32It was an amazing personal experience
31:35for Steve and I and the way we did it.
31:38Steve was an amazing clinician,
31:40you know, one of the best clinicians
31:43I've ever come in contact with.
31:44You know,
31:45when you were interviewed by Steve,
31:47you just felt you had to tell
31:50things about yourself.
31:51And and in an environment that felt
31:53safe and and Steve was so insightful.
31:55So when we interviewed the POW,
31:59Steve mainly interviewed and I
32:01would pop in now and then ask me
32:03a question and we learned so much
32:05from the POW's about resilience.
32:07We we go home at night to my house
32:11and recount what we just learned to
32:13my wife and it changed our lives.
32:17Those POW's and others became role models.
32:21To us.
32:22And so when we faced the stress in our lives,
32:26we would think back about all
32:28the resilient people we
32:30met and. Trying to learn
32:32from that experience.
32:33So, you know, I want to leave everybody,
32:36you know, with a couple of things.
32:38One, Steve was an amazing clinician.
32:41In addition to being an amazing
32:44person but unbelievable clinician,
32:45he had unbelievable insight into the nature
32:49of disease from a psychological perspective.
32:54And from a biologic point of view,
32:55we became partners.
32:57John and I kind of brought the biology.
33:00Steve, you know, became an expert,
33:03learned from it and the combination
33:06of psychological insight.
33:08And biologic insight was so very powerful.
33:13So in terms of resilience and foul stuff,
33:17we can show the first slide.
33:19The. So Steve and I.
33:23Went in with a blank slate.
33:26And as I you know mentioned,
33:28we learned from these hundreds and
33:30hundreds of of people of all different.
33:33So different groups of people,
33:35every ethnic group, every type of trauma and.
33:39Eventually we found that there were these.
33:42These factors that characterized
33:46resilience and and these are listed.
33:49We started calling it the resilience
33:51prescription and these are listed on this.
33:54Slide and they they became
33:56the basis of a book we wrote,
33:58but that's now in the 3rd edition.
34:02It it also became you know
34:04the basis for developing.
34:07Clinical approaches.
34:09To enhancing resilience.
34:12We we used this at at Sinai during
34:15the pandemic where you know when we
34:18were the epicenter of the epicenter.
34:21At one point we had over 2000
34:23patients with COVID in our hospitals.
34:28A lot of that was pre vaccine,
34:30pre understanding how to treat the disease
34:33and and so we had to develop means to.
34:36Help our frontline healthcare
34:38workers get through the stress.
34:40I know you did that.
34:41You've been doing this at Yale.
34:43And Steve and I and others at Sinai
34:45used what we had learned from our
34:47studies and resilience to develop
34:50a Center for stress resilience and
34:52personal growth and use what we learned
34:56from our resilient studies to help
34:58our frontline healthcare workers.
35:00So these are the factors that we.
35:04We identified and and personally
35:06Steve and I both. That help.
35:09It helped us personally.
35:12As some of you may know,
35:13I was the victim of a violent crime.
35:16Six years ago I was shot with a shotgun
35:21by a disgruntled former faculty member.
35:23And I didn't know if I was
35:26resilient or whether how valid the
35:28factors we came up with,
35:30and I found that they were very
35:33valid because it helped me.
35:35Recover a fully recover from that trauma
35:39in my life and Steve was unbelievable
35:43in how he dealt with. Cancer.
35:46You know, he died from prostate cancer.
35:49He was incredibly courageous and,
35:53you know, with Bernadette.
35:55Yeah, right by his side.
35:57The whole time.
35:57He got most of his treatment at Mount Sinai,
36:01and he.
36:03He became a role model for the doctors that
36:07treated him in the 3rd edition of the book.
36:12You know which is.
36:13And I'll show you in a
36:15moment which is coming out.
36:17Next next fall, but it's already written.
36:21In the epilogue, which we devoted to Steve.
36:25It it puts all the doctors that treated him.
36:28It also quotes how Steve.
36:31Was so resilient in fighting this disease,
36:34it was.
36:36It was amazing and for me as.
36:39His closest friend,
36:41it was.
36:45It was something I'll never forget.
36:47So I want you to all remember Steve as.
36:51In a very full way, you know,
36:53not not just as a fantastic clinician,
36:57a wonderful science that has impacted
37:00the field, as John mentioned,
37:02but as an amazing person that
37:04can be a role model for you.
37:07Even though he's gone.
37:10We can go to the next slide.
37:15So you know, as I mentioned,
37:16Steve and I were buddies.
37:18That's that's the 1st edition of our
37:22book and this was at a book signing.
37:26Yeah, amazing. Next slide.
37:30Now, we did a lot of things together,
37:32you know, outside of work.
37:34We actually another thing
37:35that Steve taught me. I I.
37:39I was a rower, you know,
37:41a scholar, and Steve said to me,
37:43you know, you would have a lot
37:45of fun learning how to kayak.
37:47And for the next 30 years,
37:49Steve and I kayak together and.
37:52We we did many races, you know,
37:56around the Northeast and
37:57this was a race that we did.
37:59In night in 2005 and just, you know.
38:04For a crazy reason,
38:05we got on the cover of the Newton tab,
38:08which is a a newspaper outside of Boston.
38:11This was the run of the Charles Race
38:14and this is Steve and I coming out of.
38:17Of the water doing what's called a Portage,
38:19you know, taking the boat from
38:21one part of the river to another.
38:23This is the Charles River.
38:27Never forget that.
38:28That race.
38:28Next slide.
38:32And. This is the last time we kayaked
38:36together and this was in the fall of 2021.
38:42And and Bernadette took this picture.
38:44We went kayaking with Bernadette.
38:46That's, that's my son on the right, Alex,
38:49who's now a faculty member at Mount Sinai.
38:53That's Steve in the front,
38:54and here he is, kayaking. You know,
38:57he's got metastatic prostate cancer.
39:00But that was Steve.
39:02And actually,
39:02he was great in the water.
39:03He was great athlete.
39:07And then the next slide.
39:10So Steve died and then?
39:13A few days after Alex.
39:21Went to the same spot.
39:24Just to remember, Steve.
39:27So that was a couple days after he died.
39:31And you can cut down the slides then.
39:37So. Steve is somebody that I'll never forget.
39:40He's inside me and he's inside so
39:43many of you that have got to know him.
39:46It was a privilege.
39:47A privilege to, you know,
39:49Bernadette, who we still are,
39:51still stay in contact with.
39:54I'm a Bruce Springsteen fan.
39:56As many of you know,
39:58he wrote a song called Terry Song about
40:02somebody he lost and aligning that.
40:05Song that is gives me.
40:10It makes me feel a little bit better
40:12and to remember Steve, and that is
40:14love is a power greater than death.
40:16And that's why we'll never forget Steve.
40:21So thank you for the privilege
40:23of talking about.
40:24Have mean, Steve.
40:25Thank you, rob.
40:27Thank you so much, Dennis.
40:36OK, so far our last presentation,
40:38I'm going to talk about some of
40:41the quantitative epidemiologic,
40:42genetic and epigenetic work that Steve,
40:45our colleagues and I have
40:47done specifically in U.S.
40:49military veterans and this will
40:51feature mostly my presenting on
40:53the work and then Janicza Montalvo
40:56Ortiz will present on some of
40:59the genetic epigenetic studies.
41:01So today Steve and I and our colleagues
41:03have published over 150 papers together.
41:05I went back and calculated this
41:07works out to about one per month.
41:09We were an incredible dynamic duo
41:12where Steve would often conjure up all
41:14kinds of ideas and I was the one who
41:15went to the data and and looked to see
41:17if we could resurrect some of those findings.
41:20Our work primarily centered on the
41:22psychosocial and genetic epidemiology
41:24of trauma related disorders,
41:26but also on resilience and and
41:28salutogenesis outcomes related
41:29to resilience like successful.
41:30Aging we intentionally,
41:32as Dennis mentioned with Steve's
41:34background in clinical psychiatry,
41:37took out translational approach in this work.
41:39So we were interested both
41:40in the backward translation,
41:41for example,
41:42looking at genetic and and neural
41:45biomarkers of PTSD symptom dimensions,
41:47but also forward translation.
41:48You know, we don't do epidemiology
41:50strictly for bean counting.
41:52You know,
41:52we want to identify modifiable risk and
41:55resilience factors that could be targeted
41:58in prevention and treatment efforts.
42:00As is often the case in trauma research,
42:01we've studied a number of different
42:04trauma affected populations of
42:05most notably military veterans,
42:07but also World Trade Center first
42:09responders and most recently,
42:11COVID-19 frontline healthcare workers.
42:13These are two mottos that are pervaded
42:15the work that Steve and I and our
42:18colleagues did over the years that,
42:20you know,
42:20we wanted to to focus not only on
42:22fixing what's wrong in trauma survivors,
42:24but also building what's strong and and as,
42:26as Dennis shared, you know,
42:27character traits and resilience
42:29factors and people affected by trauma.
42:31And then also on phasing,
42:33on growing through,
42:33what one goes through this
42:35idea of post traumatic growth,
42:36which I'll describe in a moment.
42:39So when one does a literature research,
42:42literature search,
42:42just even thinks about the words
42:44that come to mind when we think
42:46about post traumatic stress disorder,
42:47we're we're highly, highly negatively biased.
42:50You know,
42:50things like fear and numbing flashbacks,
42:53helplessness. It's quite overwhelming.
42:54And it's actually surprising in a way,
42:57given that most people who are
42:58affected by trauma are resilient.
43:00And this includes even people who are
43:02very highly exposed to traumatic events,
43:05as Dennis mentioned,
43:06and special forces communities.
43:08But also in natural disasters.
43:09I mean,
43:10we have this natural tendency to bounce back.
43:12And what Steve was very interested in
43:15learning are what are those ingredients
43:17that go into making people resilient?
43:20So one approach that we took to
43:22trying to understand this was
43:24to study this in large,
43:25nationally representative
43:27prospective cohort studies.
43:29So we we design now more than 10 years ago,
43:31the National Health and
43:33resilience and Veteran study,
43:34which to date now has recruited 3 separate
43:37prospective cohorts of US veterans.
43:39And as is often the case
43:40in epidemiologic studies,
43:41we wanted to look at the prevalence and
43:43correlates of major psychiatric disorders,
43:45but also trying to quantify
43:47and operationalize these more.
43:49Nebulous constructs like resilience and
43:51healthy aging and even post traumatic growth.
43:54And then we had a number of secondary aims.
43:56As as Janicza will describe in a moment,
43:58I'm looking at genetics and
44:01epigenetics of common disorders.
44:03This is a busy slide.
44:04The the only thing that's most
44:06relevant here I think is to to say
44:08that we've now recruited more than
44:098000 veterans into these studies.
44:11These are all prospective cohorts.
44:14Our most recent cohort was
44:16recruited before the COVID pandemic.
44:18So we had the rare opportunity
44:19to see how the pandemic affected
44:21mental health and we just recently
44:23completed a three-year follow-up
44:25of that cohort on 2 weeks ago.
44:27And so these samples are drawn
44:28from a very high quality survey
44:30research panel that's designed
44:31to be representative of the.
44:33The US Adult USA adult household population.
44:37And then we also apply post
44:40stratification weights to ensure that
44:42our results are generalizable to
44:44the US veteran population at large.
44:46So this is just a sample of some of the
44:49the studies that we've published over
44:51the years on the topic of resilience.
44:53And when one gets into this literature,
44:56it's surprising just how complicated
44:57it is to define what one means
45:00when we say resilience.
45:01So these are the two definitions
45:03that Steve embraced, and one,
45:05the first, is from the American
45:07Psychological Association,
45:08which defines resilience as a process of
45:11adapting well in the face of adversity,
45:13trauma, tragedy, threats or even
45:16significant sources of stress.
45:18Steve also liked the definition
45:19from George Vallant,
45:20a psychiatrist at Harvard,
45:22who described resilient individuals as those
45:25who resemble a fresh green living twig.
45:28When twisted out of shape,
45:29such a twig bends but does not break.
45:32Instead,
45:32it springs back and continues to grow.
45:37So we took,
45:37and this was largely on Steve's urging,
45:39a bottom up data-driven approach.
45:41So we allowed the data to tell us how
45:43it's organized when we consider the
45:45role that trauma has on mental health.
45:48And so we took a number of these
45:50data-driven analytic approaches.
45:51Our cluster analysis is the one I'll
45:54show today where we simply submitted
45:56a count of lifetime cumulative
45:58traumatic adversities really across the
46:00entire lifespan and then a composite
46:02measure of psychological distress
46:04given that trauma does not simply.
46:06Yield on a potential increase
46:08in PTSD symptoms,
46:09but may also lead to an uptick in in major
46:12depressive and generalized anxiety symptoms.
46:14More recently,
46:15we've been employing these
46:17discrepancy based resilience scores,
46:18which computes at a population level
46:20ones expected score given their trauma
46:23burden and their actual or observed score.
46:25And you could compute relative resilience
46:27scores at an individual level.
46:29And for longitudinal data,
46:30we published several studies now using
46:32latent trajectory modeling,
46:34which allows us to characterize predominant.
46:36Trajectories of how one might respond
46:39to trauma, and then, in particular,
46:41given the translational emphasis,
46:43we were interested in comparing the
46:45resultant groups on demographic,
46:47military, trauma,
46:48health and psychosocial variables.
46:51This is from a longitudinal
46:53study of veterans,
46:54the first nerves cohort study first in 2011,
46:57where we did a cluster analysis and
46:59we found that the majority of veterans
47:01are minimally trauma exposed and have
47:03minimal psychological distress symptoms.
47:06But then there were these other
47:08two groups that emerged at 27.5%
47:10were in this resilient group,
47:11and they were matched with regard to
47:13how much trauma they have endured
47:15over the course of their lives
47:17relative to a distressed group,
47:18about 12% of the sample.
47:20Importantly.
47:21Steve would always emphasize this is
47:23resilience is not a marker of low exposure.
47:26There has to be a prerequisite
47:28of high level of trauma burden
47:29in order to be resilient.
47:31So this clearly shows both of these
47:33groups being significantly tested by
47:35cumulative trauma burden by having
47:37very different psychological outcomes.
47:39And if you look at the the average
47:41score in the resilient group,
47:43it's on par with our minimally
47:45exposed control group when we look
47:47at screen positive rates for PTSD,
47:49MDD and GAD, both 3/4 of our.
47:52The stress group is screening positive
47:54and not a single person in the
47:56resilient group is screening positive.
47:58And not all traumas are created equal.
48:00So when we look at the trauma profiles,
48:02they're strikingly similar.
48:03In fact,
48:03our resilient group was actually
48:05more likely to have reported in
48:07during a natural disaster.
48:08But other than that,
48:10we see a striking similarity in terms
48:12of the degree of trauma exposure.
48:15And then when we looked at wave one
48:16predictors of resilience over time
48:18relative to the distressed group,
48:20not surprisingly the resilient
48:21veterans had a lower likelihood of
48:24early life psychiatric disorder.
48:25So this is, if you will,
48:26the inverse of stress sensitization.
48:29They were also physically healthier.
48:30And then what was of most interest to
48:32us is these modifiable characteristics.
48:35So they scored higher on measures
48:36of emotional stability.
48:37So a personality characteristic
48:39characterized by a high degree of
48:41emotion regulation and also these protective.
48:44Psychosocial traits,
48:45some of which are Dennis,
48:46showed in the resilience factors,
48:47in particular having a strong sense
48:49of purpose, dispositional gratitude,
48:51and a high sense of Community integration.
48:54And finally,
48:55and this was a resounding theme
48:56in the work that Steve and I did,
48:58and we actually have a perspective
49:00piece that we finished before he
49:02passed away that's currently under review,
49:04underscoring the importance of social
49:07connection and social integration,
49:09and in particular having a
49:11secure attachment style,
49:12having a strong social support network.
49:14And and deriving a high sense of
49:16emotional support from that network.
49:20And so now I'm going to
49:23introduce Janissa Montalvo Ortiz,
49:24who's been our collaborator with our
49:27colleagues on genetic and epigenetic,
49:30NHRS and nerve studies.
49:31Joga Lerner is the the lead on the
49:34the molecular studies that we've been
49:36doing and we've also been collaborating
49:39with Renado Pullmantur's group.
49:40Janita is an assistant professor
49:43in our department and also a
49:45research biologist with the Clinical
49:47Neuroscience division of the
49:49National Center for PTSD. Pizza.
49:51Thank you, Rob,
49:52and thank you for including me.
49:54It's an honor to be included in the grand
49:58rounds in honor of Doctor Southwick.
50:01So I'll be presenting data.
50:03All of this data is from the NIH RDS cohort,
50:06so it's tailored to understand
50:10better the veteran population.
50:12So we concentrated in looking at
50:15epigenetics to understand better the
50:17role of gene by environment interplay
50:19and for this we first conducted.
50:21And the pigeon?
50:23The pigeon of Wide Association
50:26study in 1135 made veterans of
50:29European ancestry and look at
50:32both current and lifetime PTSD.
50:35I'm showing their um Manhattan plots
50:38where you can see the different
50:40genes that were identified and from
50:43these we were able to replicate
50:45the gene SNP 7 in an independent
50:48cohort of 608 mile veterans from
50:51the backs biobank cohort.
50:54DNA methylation levels at this
50:56gene were found to be decreased
50:58in PTSD cases in both cohorts.
51:01To assess the functionality
51:03of these findings,
51:04we evaluated the patterns of gene
51:06expression of CE NP7 in human
51:09postmortem brain samples from
51:10the national PTSD Brain bank,
51:12and we found that this gene is
51:15differentially expressed in the
51:17medial orbital prefrontal cortex,
51:18showing a significant decrease in PTSD.
51:23This gene is known to be involved
51:25in transcription regulation,
51:26but more interestingly,
51:27genetic variants identified
51:29in Jewish studies have found
51:31associations with risk taking
51:33behavior and alcohol consumption.
51:38We also evaluated DNA methylation
51:40aging in this cohort.
51:42This work it's led was led by
51:44Amanda Teman and Peter now.
51:47Epigenetic clocks are known to be
51:49associated with disease and mortality risk,
51:52and in this cohort we found that
51:54nearly one in five male US veterans had
51:58accelerated DNA methylation age with
52:00an average of eight years older than
52:03chronological age by evaluating social,
52:06demographic, military, health,
52:08and psychosocial variables.
52:09We found diabetes and child sexual
52:12abuse as the strongest correlates,
52:14each explaining 1/3 of the variance.
52:17We also found associations with
52:19negative beliefs of aging,
52:21as well as hypertension and body mass index.
52:25By evaluating grim age,
52:26which is a recently developed
52:28epigenetic clocks that is known
52:30through outperforms other clocks in
52:32predicting mortality and disease risk,
52:35and evaluating PTSD symptoms
52:37and different types of trauma,
52:39we found that PTSD was associated
52:42with twofold greater odds of
52:44accelerated DNA methylation H,
52:46which aberration nearly a full decade.
52:49Associations were also observed with
52:52greater severity of trauma related
52:54detachment and sleep disturbances.
52:58And lastly, we also asked the
53:00question of whether genetic variation
53:02associated with PTSD risk may be
53:05influenced by environmental factors.
53:07This work was led by Amanda Tamon and in
53:10collaboration with Renato's Polianthes
53:12Group for these polygenic risk course,
53:15which is a summary of the genetic
53:18associations calculated based on
53:20recent large scale genome wide
53:22association studies and evaluating
53:24the effects of attachment style.
53:26We found that attachment style moderates.
53:28The polygenic risk for both
53:31lifetime and current PTSD.
53:33When evaluating polygenic risk
53:34of different PTSD symptoms,
53:36we found that higher reexperiencing
53:39PRS is associated with greater
53:41severity of PTSD symptoms,
53:44and this was an effect of served only in
53:47veterans with an insecure attachment style.
53:49We also evaluated this using a Jeep
53:52IE model and found that PRS by
53:55attachment style interaction was
53:57associated with greater severity.
53:59Of PTSD symptoms to disentangle the
54:03relationship between attachment
54:05style and PTSD and investigate
54:08potential causal effects.
54:09We conducted middler randomization
54:11analysis and found that these
54:14relationship was actually bidirectional.
54:17In summary,
54:17the work described showed the
54:19contributions in the understanding of
54:21the biological underpinnings underlying
54:23the gene by environment influences on PTSD,
54:26specifically in a US veteran population.
54:31Thank you so much, Janice.
54:32And I'll also just comment when I
54:34first showed Steve these figures,
54:36how excited he was given just
54:38how powerful the effect of social
54:40connection and in this case attachment
54:42style has been in our studies and
54:43to to here to show basically that
54:45it's even under conditions of
54:47very high polygenic risk for PTSD,
54:50you basically don't see an
54:52elevation and risk for the disorder.
54:54So he was absolutely ecstatic
54:56about this finding.
54:58So in the next section,
54:59I'm going to go back to this negative
55:01bias that we've had in the the trauma
55:04literature and is this question that
55:06PTSD is it always doom and gloom?
55:08So as you saw when I started with the
55:11slide on all the negative concepts
55:13associated with people with PTSD,
55:15there's a preponderance of evidence
55:17negatively valenced in this literature
55:19linking PTSD to negative outcomes.
55:21So this includes psychiatric
55:23comorbidities and suicide,
55:25physical health problems
55:26such as cardiovascular.
55:28Disease and functional difficulties
55:29in various life domains and
55:31as janita just mentioned,
55:33also has been linked to a twofold
55:35increase in accelerated epigenetic aging.
55:37And there's also evidence linking
55:40PTSD early mortality.
55:41But one of the questions that
55:42Steve and I are very interested
55:44in is could there potentially be
55:46a silver lining to PTSD?
55:48Is it possible that living with PTSD
55:51may help foster positive psychological
55:54changes and potentially also
55:57resilience to subsequent traumas?
55:59So this is not a new idea.
56:01This notion that suffering can be
56:03potentially transformative has
56:04been embraced by ancient spiritual
56:07religious traditions, literature,
56:08philosophy,
56:09and ideas and writings of ancient Hebrews,
56:11Greeks, early Christians,
56:13as well as teachings of Hinduism,
56:15Buddhism and Islam.
56:18For example,
56:19the Greek philosopher Aristotle
56:20said that it is during our darkest,
56:23darkest moments that we must focus
56:26to see the light.
56:28The philosopher Charlie Brown has
56:30also tried to convince Lucy that
56:32adversity is what makes us mature.
56:35The growing soul is watered best
56:38by tears of sadness.
56:41So we've published a number of
56:42articles in this area as well
56:44and including some of the first
56:46nationally representative studies to
56:48look at post traumatic growth in a
56:50population based sample of military veterans.
56:53And most recently and and Steve was
56:55very proud of this paper showing
56:58that the the pandemic was associated
57:00with positive psychological changes.
57:03So what is this idea of post
57:05traumatic growth?
57:06So these are positive,
57:08meaningful psychological changes
57:09that an individual can experience
57:12as a result of struggling with
57:14traumatic and stressful life events.
57:17These are the various domains
57:18that have been identified.
57:19The first five have been or considered the
57:22original dimensions of post traumatic growth,
57:24increased appreciation of life,
57:26greater sense of personal strength
57:28and coping,
57:29self efficacy,
57:29embracing a future paths for one's life.
57:32We're seeing new possibilities after trauma,
57:35experiencing a renewed appreciation
57:37for interpersonal relationships,
57:39positive spiritual changes and the
57:41the two here were actually added more
57:43more recently in the past five years
57:45or so that one might experience.
57:47Increase in compassion and altruism and
57:49and and a tendency to want to give back
57:52to others and also creative growth.
57:54And this came up largely in the context
57:56of the pandemic where many individuals
57:59took on new hobbies and interests.
58:01And one of our earlier studies we
58:04found that 50% of veterans reported
58:06experiencing post traumatic growth and
58:08some of the independent correlates
58:10and drivers of post traumatic growth
58:13interestingly were re experiencing
58:15or intrusive symptoms of PTSD.
58:17Which suggests that there has to
58:19be this struggle with the trauma,
58:20which potentially can then lead to
58:22a reappraisal of it and potentially
58:24also a reintegration of that traumatic
58:27experience into one's life narrative.
58:29Importantly this has to happen in
58:31the context of support of others.
58:33Rich Tedeschi and others who have
58:35largely developed this concept have
58:37long argued for the importance of
58:39social connection and strong sense of
58:41purpose and these solution genic factors.
58:43And similarly we see these emerging as
58:46key correlates of post traumatic growth.
58:50When we look among veterans with PTSD,
58:53they're actually more likely to
58:54experience post traumatic growth.
58:56We see about 3/4 of veterans with
58:58PTSD who were poor,
59:00at least moderate or higher levels
59:01of post traumatic growth.
59:03And this was Steve's idea to say,
59:05even in the context of PTSD,
59:07if you have post traumatic growth,
59:08are you functioning better?
59:09And indeed, that does happen to be the case.
59:12Veterans who had PTSD and post traumatic
59:14growth actually scored better on
59:16measures of mental functioning than
59:18those with PTSD who did not have.
59:20Post traumatic growth and So what we observe,
59:23and these are empirical data where we
59:25try to fit the the the association
59:27between the level of PTSD symptom
59:29severity and post traumatic growth,
59:31we see this inverted U-shaped association.
59:34So growth is really maximized right
59:37around this moderate threshold of
59:39PTSD symptoms.
59:40And so if you have too few symptoms,
59:42there's really nothing to grow from and
59:44once you exceed a certain threshold,
59:46you've reached the point of
59:47diminishing return.
59:48So really this is the sweet
59:49spot of post traumatic growth.
59:51Just right around that moderate threshold.
59:53And interestingly,
59:53this happens to be right around the
59:56threshold that we typically impose
59:57for a positive screen for PTSD.
01:00:01Importantly, we've also found that post
01:00:04traumatic growth can fluctuate over time.
01:00:06About 60% report stable post traumatic
01:00:08growth over a two year period,
01:00:10and it's maintained by PTSD symptoms,
01:00:13most notably intrusive thoughts.
01:00:15But also these Saluda genic
01:00:17factors purpose in life,
01:00:18altruism, gratitude, religiosity,
01:00:20and active lifestyle,
01:00:22which is likely linked to active coping.
01:00:26And this is a question that that
01:00:28Steve posed and we ended up being
01:00:30very interested and he was very proud
01:00:32of this finding is that is post
01:00:35traumatic growth an end in and of
01:00:37itself or can it serve potentially as
01:00:39somewhat of a psychological shield,
01:00:41if you will,
01:00:42to promoting resilience to
01:00:44subsequent traumas?
01:00:45And so we looked at this empirically
01:00:47using the longitudinal nerves data set
01:00:49and we found that indeed veterans who
01:00:51reported a greater sense of personal
01:00:53strength in relation to a trauma that.
01:00:56Occurred more than 25 years earlier,
01:00:58we're actually substantially less likely
01:01:00to develop PTSD to a new traumatic event,
01:01:03and this is a pretty strong effect.
01:01:05For each standard deviation unit increase,
01:01:07we saw a 32% lower likelihood
01:01:10of developing PTSD.
01:01:12So it's underscores the importance
01:01:14I think of looking at these
01:01:16constructs interchangeably.
01:01:17So resilience, post traumatic growth,
01:01:19PTSD and what it suggests to us
01:01:21is that post traumatic growth even
01:01:23in the presence of Co occurring.
01:01:26PTSD symptoms may help an individual
01:01:28develop coping skills to better
01:01:30manage subsequent traumas.
01:01:32There's now a program that's been
01:01:34developed called Boulder Crest
01:01:35by Rich Tedeschi, Steve and I.
01:01:37Unfortunately, before he passed,
01:01:38we we, we hadn't.
01:01:39We had reached out to rich to to
01:01:41potentially go there and actually
01:01:42experience the training.
01:01:43And these are veterans who've tried all
01:01:45kinds of treatments and nothing's worked.
01:01:46But the BOULDERCREST program
01:01:48really centers around the themes
01:01:49of post traumatic growth.
01:01:50It's not pushing the trauma away,
01:01:52but growing from it,
01:01:53benefiting from it and moving
01:01:55on and incorporating it.
01:01:56Into one's life.
01:01:59I also want to comment on Steve.
01:02:01Just incredible contributions and
01:02:03productivity during the COVID pandemic.
01:02:07Steve was a member of the Yale
01:02:09COVID-19 Mental Health Task Force,
01:02:10the Mount Sinai COVID-19
01:02:12mental health research team,
01:02:13which he of course wrote me into and
01:02:16was heavily involved in in several of
01:02:18our national studies on US veterans.
01:02:21I looked and and she's published 18 papers,
01:02:24including three perspective pieces,
01:02:26including one incredibly well
01:02:28written and and, you know,
01:02:30forward Thinking Piece published in JAMA on
01:02:33the pandemic related post traumatic growth.
01:02:37Highly encourage folks to read that if
01:02:39they're interested in this concept.
01:02:41And of course he was doing this all
01:02:43while undergoing intensive treatment
01:02:44for metastatic prostate cancer.
01:02:46Absolutely amazing.
01:02:47I'm going to play a brief clip
01:02:50on video clip of Steve.
01:02:52I think we need his voice with us.
01:02:54This was from last year's grand
01:02:56rounds when John had asked for
01:02:58members of the faculty and and staff
01:03:00and Yale psychiatry to describe
01:03:02what the pandemic meant to to them.
01:03:05And what really strikes me about
01:03:06this is just.
01:03:07So grateful Steve was to be involved
01:03:09and to be part of the teams that were
01:03:12involved in doing research around the
01:03:14COVID pandemic and the response to it.
01:03:25Everyone. With you.
01:03:30I retired over two years ago.
01:03:34During my entire social movie revolved around
01:03:37the outside psychiatry department and the.
01:03:41He no longer had a novels.
01:03:44Good reasons to visit him.
01:03:47On regular basis.
01:03:49And with the start of COVID, it looked as
01:03:52if the situation would get even worse.
01:03:55I also started to feel guilty about not
01:03:58being in the hospital on the front line.
01:04:01I mean no way to contribute.
01:04:05I like being on the front line.
01:04:08And felt that my role as a physician
01:04:11who caretaker. He's slipping away.
01:04:15Even when I try to internalize
01:04:18my father's lifelong model.
01:04:21I'm not OK. You're not OK.
01:04:23It's OK. I still felt pretty.
01:04:30In China.
01:04:32He asked if I would consider
01:04:35becoming a member of a COVID-19
01:04:37mental health task force.
01:04:39It's meaningful.
01:04:40And ask if I'm right joiner to give
01:04:43a talk about resilience to PA and,
01:04:46you know,
01:04:47interests.
01:04:50And I got married to them again.
01:04:53My partner is 20 years.
01:04:56I was back.
01:04:59That was my teenage.
01:05:00That was what we need since August.
01:05:03Perhaps I could contribute,
01:05:06even if in a small way.
01:05:09Which brings to mind Helen Keller's please.
01:05:13I longed to accomplish
01:05:15great and noble task,
01:05:17but it is my chief duty to
01:05:19accomplish small tasks as if
01:05:21they were great and noble.
01:05:26And recently I learned that the
01:05:29Yale Department of Psychiatry
01:05:31has been rated the number one
01:05:34department in the United States.
01:05:36Just thinking about it.
01:05:38You and I have the opportunity to work
01:05:42for great department whose clinical,
01:05:45educational and research mission is to help
01:05:49those who are suffering mental illness.
01:05:54What could be better than that?
01:05:57So this year, in a way,
01:05:59I rejoined the department
01:06:01by joining the task force,
01:06:03giving the talk with his meaning and
01:06:06also teaming up with colleagues to
01:06:09investigate the impact of the pandemic
01:06:12on frontline healthcare workers.
01:06:15Here's a passage from the manuscript
01:06:18that we recently published about
01:06:21frontline healthcare workers.
01:06:22I quote from that because it is relevant to
01:06:26how I personally experienced this past year.
01:06:32Quote. Baby seals and special forces
01:06:36teams often attribute their own courage
01:06:39and resilience to the power of team
01:06:42members who have each other's back and
01:06:45will even risk their life to one another.
01:06:49Message from healthcare leaders
01:06:51should be clear. Team, team, team,
01:06:54you are your brother and sisters.
01:06:58Team. We are all in this together.
01:07:01Fighting for a common mobile cause
01:07:04is a privilege to be working
01:07:06alongside such remarkable.
01:07:11For me, this year has been filled
01:07:15with distress and great concern
01:07:18for all those who have suffered
01:07:20from the devastating impact.
01:07:22Something came down.
01:07:24And for the toxic political
01:07:27divisions in our country.
01:07:28And for long standing and pervasive social,
01:07:32racial, economic,
01:07:34and healthcare disparities.
01:07:39This year has also been
01:07:41filled between no purpose.
01:07:43We just kind of resilient bonds.
01:07:4792 the privilege to work with
01:07:50him and care deeply about when
01:07:53wonderful colleagues who are both
01:07:56teenagers and cherished friends.
01:07:59Thank you for having my back.
01:08:07Absolutely amazing.
01:08:08Every time I watched the video
01:08:10I I think about the data and we
01:08:12see the same themes and and and
01:08:15how Steven bodied all of these
01:08:17resilience factors during the fight,
01:08:19fight for his life.
01:08:21Here are some remembrances from
01:08:22from Steve's many colleagues.
01:08:24I had an outpouring I probably
01:08:26about 200 emails that that I I I
01:08:29received after Steve had passed.
01:08:31The first is from Ilan Harpaz
01:08:33Rotem in our department,
01:08:34who said that Steve was more
01:08:36than an intellectual mentor.
01:08:37He cared for us like a father.
01:08:39I was lucky enough to have a FaceTime
01:08:41call with him several days before he passed.
01:08:43He was a fighter and reflected on resilience.
01:08:46He was an amazing mentor and spoke
01:08:48excitedly about the various projects.
01:08:51And was working on he valued
01:08:54his mentees tremendously.
01:08:55Lauren Pecoraro from Mount Sinai
01:08:57was involved in the COVID-19
01:08:59mental health research team.
01:09:01Said that Steve was a brilliant,
01:09:02kind and humble mentor and guide to us all.
01:09:05He generously gave of his
01:09:06time to help us in our work,
01:09:09even when he was ill and in pain.
01:09:11I know we will all greatly Miss
01:09:13Steve's calm and guiding presence.
01:09:16Rick for Keoni from Harvard,
01:09:17with whom Steve was developing resilience
01:09:19training programs in the past few years,
01:09:22remarked that Steve was a
01:09:24beautiful and inspiring person.
01:09:25He was always wanting to
01:09:26help in any way he could.
01:09:28There should be a picture of Steve in the
01:09:32dictionary next to the word resilience.
01:09:34And finally,
01:09:35Christine Olson,
01:09:36the Chief Wellness officer with whom
01:09:38Steve was working very closely during the
01:09:40pandemic and even prior to the pandemic,
01:09:42said that Steve made her feel seen,
01:09:44heard, valued, supported,
01:09:46developed, understood.
01:09:47He made me feel like I was
01:09:49somebody special and capable,
01:09:50showed me what it was to be resilient.
01:09:53I felt important because he shared
01:09:55himself and his life with me,
01:09:57led by example and generously
01:09:58gave of his time and wisdom.
01:10:01He was a rare,
01:10:02brilliant gem of a human being.
01:10:05I miss him so much and I know that I am
01:10:08sad and grieving because I was lucky.
01:10:10I was lucky to know him.
01:10:14And finally, these are reflections
01:10:16directly from Steve from.
01:10:17These are from the forthcoming
01:10:193rd edition of Steve and Doctor
01:10:22Charney's Book on Resilience.
01:10:25This is a direct quote from Steve,
01:10:26who said resilience has been defined
01:10:28as the ability to bounce back,
01:10:30but I can't bounce back.
01:10:33It's been defined as going
01:10:34through a traumatic situation
01:10:36without a drop in functioning,
01:10:37but I have had a drop in function.
01:10:40Does that mean I am not resilient?
01:10:44We can answer Steve's question for him.
01:10:46He was absolutely resilient.
01:10:48He inspired, supported,
01:10:50loved and lived fully.
01:10:52He let go of resentments and
01:10:54connected to sources of meaning.
01:10:56While Steve courageously fought his cancer,
01:10:58pain and physical limitations,
01:11:00he did bounce back with love,
01:11:03giving and service to others,
01:11:05the field colleagues, mentees and COVID
01:11:08frontline workers in his final months.
01:11:11Steve also reflected it on how he personally
01:11:15defined resilience toward the end of life.
01:11:17Everyone he knew well would
01:11:19agree that this is how he lived.
01:11:21Do the best you can with what you've got.
01:11:24Take it all success and failure and use it to
01:11:28the best you can in the service of others.
01:11:32In the end,
01:11:33what really matters is who and what you love.
01:11:36That's it.
01:11:37End of discussion.
01:11:38Love is the heart and soul of resilience.
01:11:46And finally, this is a Christmas card
01:11:49that I received last year from Steve May.
01:11:51May come across as a little unusual has the
01:11:54cover of Steve and Doctor Charney's book,
01:11:57as well as various pictures of Steve
01:11:59engaging and incredibly physically
01:12:01demanding activities of pushing up boulders,
01:12:04lifting trees, of boxing,
01:12:06and of course Bernadette.
01:12:07There as a cliffhanger and inside
01:12:10was this simple message that
01:12:13now when I reflect on it means.
01:12:16Much more than when I initially read it,
01:12:19it simply said hang in there you can do it,
01:12:22press on. And Bernadette,
01:12:25when I shared this slide with her,
01:12:28asked me to also add and don't
01:12:30take yourself too seriously.
01:12:31Steve always had a way to infuse humor,
01:12:34even in the darkest and and most
01:12:36challenging of life situations.
01:12:38And I think when I reflect on
01:12:40this really simple message,
01:12:41it's it's a message for all of us
01:12:43and and how Steve wanted to leave us
01:12:45with the encouragement to press on
01:12:47and forge ahead in what we're doing.
01:12:49And so, Steve,
01:12:50I'll try to say this without tearing up.
01:12:52Thank you for always having our backs.
01:12:56And for being an enduring shining
01:12:59light in our lives.
01:13:01We love you, we miss you,
01:13:02and we look forward to honoring
01:13:04and building on your extraordinary
01:13:06legacy for the rest of our lives.
01:13:09And thank you all for joining us today
01:13:11to honor our dear colleague and friend,
01:13:14Steve Southwick.
01:13:15This concludes our formal session today,
01:13:18and I'll turn it over now to Doctor
01:13:20Crystal for any final remarks.
01:13:24Thank you, rob. 1st. Rob,
01:13:29thank you for pulling all this together.
01:13:31Your. Your ability to draw on Steve's
01:13:36legacy with us and to share share this
01:13:40with us all is really greatly appreciated.
01:13:44As was the presentations from
01:13:46all the speakers today,
01:13:48from Doctor Charney and and from.
01:13:52Doctor Montalvo Ortiz.
01:13:55What a remarkable fortunate community we
01:13:59are to have known, worked with, learn from.
01:14:04Doctor Southwick. And. Um, I we will.
01:14:11He's he gives us a gift.
01:14:14That keeps us going at this really
01:14:17terribly difficult time in our culture,
01:14:20in our. You know,
01:14:22by challenging world that we live in.
01:14:26And. And. So thank you.
01:14:31To all the speakers,
01:14:34thanks to all who have joined us today.
01:14:38As we've had our respective backs.
01:14:42As we remember Steve and
01:14:45special thanks to the speakers,
01:14:47so take care of your buddy.