WELCOME TO THE CLINICAL CENTER GRAND ROUNDS,
A WEEKLY SERIES OF EDUCATIONAL LECTURES FOR PHYSICIANS AND
HEALTH CARE PROFESSIONALS BROADCAST FROM THE CLINICAL
CENTER AT THE NATIONAL INSTITUTES OF HEALTH IN
BETHESDA, MD.
THE NIH CLINICAL CENTER IS THE WORLD'S LARGEST HOSPITAL TOTALLY
DEDICATED TO INVESTIGATIONAL RESEARCH AND LEADS THE GLOBAL
EFFORT IN TRAINING TODAY'S INVESTIGATORS AND DISCOVERING
TOMORROW'S CURES.
LEARN MORE BY VISITING US ONLINE AT HTTP://CLINICALCENTER.NIH.GOV
THANK YOU ALL FOR JOINING US
TODAY ONLINE AND IN PERSON.
VERY NICE TO SEE EVERYONE HERE.
IT'S MY GREAT PLEASURE TO
WELCOME YOU TO TODAY'S CLIPICAL
CENTER GRAND ROUNDS.
THE HOPKINS CLOUD CME ARCKIVITY
CODE FOR TODAY'S GRAND ROUNDS
AND 50529.
AND TEXT THIS CODE TO JOHNS
HOPKINS CME PHONE NUMBER ON THE
SLIDE AND THEN YOU CAN RECEIVE
YOUR CME CREDIT IF ARE THIS
LECTURE.
WE KINDLY INVITE TO YOU PRORIDE
ANY FEEDBACK ON TODAY'S LECTURE
BY SCANNING THE QR CODE ON THE
CME SLIDE AND FOR THOSE APPLYING
FOR CME, YOU WILL RECEIVE A
FEEDBACK SURVEY VIA E-MAIL LINK.
THE SURVEY WILL BE USED TO
PROVIDE US WITH IMPORTANT
FEEDBACK ABOUT THIS PRESENTATION
AND ALLOWS TO YOU SUBMIT ANY
SUGGESTIONS FOR FUTURE GRANDS
ROUNDS TOPICS, FOLLOWING THE
PRESENTATION QUESTIONS FOR THE
SPEAKER WILL BE TAKEN FROM
MICROPHONES IN THE AISLES, AS
WELL AS VIDEOCAST VIEWERS MAY
SUBMIT A QUESTIONS AT ANY TIME
BY SCROLLING DOWN AND CLICKING
THE LIVE FEEDBACK BUTTON LOCATED
ON THE VIEDMANIOY CAST WEBSITE.
QUESTIONS WILL BE ANSWERED AS
TIME PERMITSA THE CONCLUSION OF
THE PRESENTATION.
SO I'M VERY PLEASED AS THE
CLINICAL DIRECTOR OF NIMH TO
INTRODUCE TODAY'S SPEAKER,
DR. PETER SCHMIDT.
HE'S THE CHIEF OF THE
BEHAVIORIAL ENDOCRINE BRANCH OF
THE NATIONAL INNSITUTE OF MENTAL
HEALTH AND HE'S THE DIRECTOR OF
THE CLINIC ON OP4.
HE EARNED HADIS BACHELORS FROM
THE UNIVERSITY OF TORONTO, HE
THEN EARNED A BACHELOR'S OF
MEDICINE AND SURGERY WITH HONORS
WITH THE ROYAL COLLEGE OF
SURGEONS IN IRELAND, AND HE
RETURNED TO THE UNIVERSITY OF
TORONTO WHERE HE COMPLETED HIS
RESIDENCY IN PSYCHEISTRY AND
CAME TO THE NIMH IN 1986, FIRST
TO THE UNIT IN PEPTIDE STUDIES
IN THE BIOLOGICAL PSYCHIATRY
BRANCH AND JOINED WHAT IS NOW
KNOWN AS THE BEHAVIORIAL
ENDOCRINE BRANCH THAT HE NOW
LEADS.
MANY MAY NOT KNOW THAT
DR. SCHMIDT ALSO SERVED AS
DREBTOR AND SOCIAL DIRECTOR OF
THE PSYCHIATRY LIAISON SERVICE
BEFORE I ARRIVED AND HE'S BEEN A
TRUSTED CLINICAL ADVISOR ON THE
OP4 ACTIVITIES AND THE IRP.
DR. SCHMIDT SERVES AS AN
ASSOCIATE PROFESSOR IN THE MOOD
PROGRAM AT THE UNIVERSITY OF THE
MARYLAND A POSITION SINCE 2000
AND ADJUNCT PROFESSOR OF THE
DEPARTMENT OF PSYCHIATRY AT THE
UNIVERSITY OF NORTH CAROLINA
CHAPEL HILL.
A POSITION HE'S HELD SINCE 2007.
HE HAS OF COURSE SERVED ON
NUMEROUS NIH COMMITTEES WRITTEN
200 PAPERS INCLUDING IN THE NEW
ENGLAND JOURNAL MANY IN THEIR
JAMA, JOURNAL OF PSYCHIATRY AND
MOLECULAR PSYCHIATRY, IF I SPEND
ALL MY TIME TELLING BUT HIS
PAPER AND AWARDS HE WOULDN'T GET
TO HIS LECTURE EMPLOY HE'S
SERVED ON THE PREMEN TRAL
DYSPHORIC GROUP, CHAIRED ON THE
SOCIETY OF NEUROPHARMA COALING
AND AT NIMH THE WORK THAT
DR. SCHMIDT AND HIS COLLEAGUES
HAVE WORKED ON HAS LED TO THE
IMPORTANT ENDOCRINE MODELS THAT
CLARIFY THE ROLE OF REPRODUCTIVE
HORMONES OF MOOD DEVELOPMENT
DISORDERS IN WOMEN.
HIS LABORATORY STUDIES, THE
RELATIONSHIP BETWEEN HORMONE
STRESS AND MOOD PARTICULARLY IN
THE AREAS OF POSTPARTUM,
DEPRESSION, SEVERE PREMENSTRUAL
DYSPHORIA AND PERIPAUSAL
DEPRESSION, HIS LAB BEGAN
INITIATIVE TO LONGITUDINALLY TO
THE DEVELOPMENT EFFECTS OF SEX
STEROIDS DURING PUBERTY, I
APPRECIATE HIS RIGOR AND
MENTORING, TODAY HE WILL PRESENT
HIS LECTURE ENTITLED DEPRESSION
DURING PERIMENOPAUSE, ENDOCRINE
CHARACTERISTICS.
PLEASE JOIN ME IN WELCOMING
DR. SCHMIDT.
[ APPLAUSE ]
>> THANK YOU MARILYN FOR THOSE
GENEROUS COMMENTS AND I'M DPLAD
OUR CONVERSATIONS HAVE BEEN
MUTUALLY USEFUL.
JUST TO GET STARTED I HAVE
NOTHING TO DISCLOSE.
I WILL BE MENTIONING IN PASSING,
THE USE OF EXPERIMENTAL USE OF
AN ESTROGEN RECEPTOR BETA
AGONIST IN THE TREATMENT OF
POTENTIAL TREATMENT OF
PERIMENOPAUSAL DEPRESSION.
LEARNING OBJECTIVES WILL BE
FOCUSING ON THE RELATIONSHIP, OR
STUDIES ON THE RELATIONSHIP
BETWEEN DEPRESSION AND THE
PERIMENOPAUSE.
SO MUCH OF OUR WORK IN THE
CLINIC AS FOCUSED ON
REPRODUCTIVE MOOD DISORDERS BUT
AS MARILYN MENTIONED, WE'VE ALSO
STARTED AN INITIATIVE IN
COLLABORATION WITH KAREN BERM AN
AND JACK AND LINNET, AND TRYING
TO UNDERSTAND THE IMPACT OF THE
PHYSIOLOGIC EVENTS RELATED TO
PUBERTY ON NORMAL BRAIN
DEVELOPMENT OR TYPICAL BRAIN
DEVELOPMENT.
MOST OF MY WORK OVER THE LAST
DECK'SS HAVE FOCUSED ON 2
QUESTIONS, FIRST, IS ARE THESE
REPRODUCTIVE MOOD DISORDERS
LINKED TO THE PERIODS OF
REPRODUCTIVE ENDOCRINOLOGY IN
WHICH THEY ARE REPORTED TO
OCCUR.
AND SECOND, IF THAT'S THE CASE,
THEN WHAT WOULD BE THE MECHANISM
WHEREBY A CHANGE, OTHERWISE AH
TENSIBLY NORMAL CHANGE THIS
PHYSIOLOGY WOULD TRANSLATE INTO
AN ALTERATION IN MOOD STATE IN
THESE WOMEN.
SO THESE ARE THE CONDITIONS THAT
WE STUDY.
PERPERIMEN PAUSAL DEPRESSION,
PERIMENSTRUAL DISORDER,
POSTPARTUM DEPRESSION, KAREN AND
I ARE STARTING A NEW INITIATIVE
ON POSTPARTUM PSYCHOSIS.
SO THESE CONDITIONS ARE
PREVALENT, THEY'RE ASSOCIATE
WIDE CONSIDERABLE DISABILITY,
THEY OCCUR IN WOMEN AT DIFFERENT
PHASES OF THEIR LIFE CYCLE.
BUT THEY'RE NOT FROM WHAT WE
UNDERSTAND THE SAME CONDITION
AND IN CONTRAST TO TYPICAL
ENDOCRINE OPEN MEETINGATHY SAY
HYPO OR HYPER THYROIDISM WHERE
BRAIN SYMPTOMS CAN OCCUR IN SOME
PEOPLE WHO HAVE TOO HIGH OR TOO
LOW THYROID HORMONE.
THERE'S NO EVIDENCE OF
DEFICIENCY OF EXCESSIVE HORMONE
IN ANY OF THESE CONDITIONS AND
THERE'S BEEN MULTIPLE STUDIES TO
KIND OF CONFIRM THAT, SO THESE
ARE NOT TYPICAL ENDOCRINE
OPERATING GLOBALLYATHYS PER SE,
WHAT WE HAVE NOTICED IS ACROSS
ALL THESE CONDITIONS IS A TERM
CALLED THE DIFFERENTIAL
SENSITIVITY WHICH IS NOT
UNFAMILIAR IN ENDOCRINOLOGY OR
ANY OTHER BRARCH BRAP OF
MEDICINE WHERE THE SAME CHANGE
IN A HORMONE ELICIT A CHANGE IN
WOMEN THAT ARE AT RISK THAT'S
UNSEEN AND IN UNAFFECTED WOMEN.
HOWEVER THE HORMONE AT CHANGE
DIFFERS ACROSS THE CONDITIONS
WHERE MAYBE THE EXPOSURE TO
HORMONES THAT TRIGGER TRIGGER
SYMPTOMS AND PREMENSE STRAL
DYSPHORIC DISORDER WHERE IT
SEEMS TO BE THE WITHDRAWAL OF
HORMONES IN SYMPTOMS AND
POSTPARTUM DEPRESSION OR AS I
WILL SHOW YOU LATER IN MY TALK,
PERIMENOPAUSAL DEPRESSION.
SO WHAT I WILL DO TODAY IS
FOCUSING ON REALLY, OUR TODAYS
ON THE RELATIONSHIP BETWEEN
DEPRESSION AND THE MENOPAUSE
TRANSITION OR THE PERIMENOPAUSE.
I'LL TALK ABOUT OUR WORK IN THE
LONGITUDINAL STUDY FOLLOWING
PERSPECTIVELY, WOMEN AS THEY GO
THROUGH THE MENOPAUSE
TRANSITION, STUDIES ELECTRICKING
AT THE EFFECTS OF
ESTRADISCIPLINARYOLE WITHDRAWAL
IN MOOD SYMPTOMS IN THESE
MENTION AND A BREF MENTION OF AN
ONGOING TRIAL WHERE WE'RE
LOOKING AT THE EFFECTS OF AN E.
R. BETA AGONIST IN THIS
CONDITION AND THEN I WILL END
THIS WORK THAT WE DO IN
COLLABORATION WITH DAVID
GOLDMAN'S LABORATORY WHERE WE
TRY TO DEVELOP INVITRO MODELS TO
RECAPITULATE THE HORMONAL
EXPERIMENTS WE DO IN THE CLINIC
AND TRY TO UNDERSTAND SOME OF
THE CELLULAR, UNDERLYING
CELLULAR BIOLOGY AND SIGNALING
THAT MAY BE PRESENT IN THESE
WOMEN.
SO JUST TO START WITH, BACK IN
2000, PRIOR TO THAT THERE IS NOT
MUCH OF AN AGREEMENT OR
CONSENSUS ON WHETHER THERE'S ANY
ASSOCIATION BETWEEN DEPRESSION
AND MENOPAUSE.
AND THAT WAS LARGELY RELATED TO
WORK DONE IN A CONDITION CALLED
INVOLUNTEERSUTIONAL MEL AN
ALCOHOLLIA, BUT SEVERAL STUDIES
THAT WERE COMMUNITY BASED, LARGE
SCALE, PROSPECTIVELY FOLLOWING
WOMEN AS THEY WENT THROUGH THEIR
REPRODUCTIVE STATES THROUGH
THEIR LAST MENSTRUAL PERIOD,
IDENTIFIED THAT FOR SOME WOMEN,
THIS WAS A PERIOD OF INCREASED
RISK FOR DEPRESSION.
IN FACT, THERE WAS A 2-3 FOLD
INCREASED RISK OF BOTH FIRST
ONSET, SO IT'S NOT JUST WOMEN
WHO HAD A PREVIOUS DEPRESSION,
BUT ALSO RECURRENT DEPRESSIONS.
SO THAT SUDDENLY
SHOWED--DEMONSTRATED A SIGNAL
THAT WAS PRESENT BUT IT WAS NOT
IN THE POST MENOPAUSE, IT WAS IN
THE TRANSITION FROM REPRODUCTIVE
LIFE TO THE MENOPAUSE.
THE ESTIMATES ARE THAT THIS MAY
OCCUR IN 20-30%.
SO WHAT'S CLEAR IS THAT THE MAR
JORRITY OF WOMEN GO THROUGH THE
MENOPAUSE TANSITION WITHOUT
DEVELOPING ANY KIND BE OF
AFFECTIVE OR MOOD DISTURBANCE.
FOR SOME IT CAN BE VERY
IMPORTANT.
ADDITIONALLY FROM THE WOMEN'S
HELT INITTIAIVE IT AND OTHER
STUDIES SHOWED THAT EVEN THE
PRESENCE OF MINOR DEPRESSION IN
A PERIOR POST MENOPAUSAL WOMEN
THAT OVER A 5 YEAR FOLLOW UP
PERIOD CONTROLLING FOR OTHER
RISK FACTORED SHOWED A 50%
INCRACY IN CARDIOVASCULAR
MORTALITY SO THIS IS SOMETHING
THAT IS IN THE SICKIATRIC
LITERATURE WHERE THERE'S A
CLUSTERING OF DEPRESSION,
METABOLEC DYSFUNCTION AND HEART
DISEASE AND GIVEN THAT THIS IS
THE HEART DISEASE IS THE NUMBER
1 CAUSE OF MORTALITY IN WOMEN AT
THIS AGE, THAL SEEMED TO BE A
PRETTY IMPORTANT POTENTIAL
MEDICAL SEQUELA OF DEPRESSION
DURING THE PERIMENOPAUSE AS WELL
AS EMOTIONAL DISABILITY THAT
ACCOMPANYS IT.
SO WHAT HAPPENS DURING THE
MENOPAUSE?
AS YOU KNOW WOMEN WITH OVARIES
ARE BORN WITH ABOUT 400, 500,000
PRIMORDIAL FOLLICLES IN THEIR
OVARIES AND THERE'S AN ATTRITION
OF THESE OVER THE COURSE OF YOU
KNOW EACH OFUE LATTERY CYCLE AND
WITH AGE.
HOWEVER, THERE IS A RAPID
DECLINE AT AROUND AGE 40,
MIDLIFE IN WOMEN THAT IS RELATED
AND ULTIMATELY ENDS IN THE
MENOPAUSE.
NOW THIS IS A SLAYED I BORROWED
IN JAN HALL WHO'S DOWN IN NORTH
CAROLINA MANY YEARS AGO SO THIS
IS A KEEMATTIC OF THE 3, OF THE
LEVELS OF CONTROL OF
REPRODUCTIVE AXIS AND GNRH IS
STIMUTING THE PITUITARYY FOR LH
AND FSH, WHICH STIMULATE THE
OVARY.
THE OVARY PRODUCES A NUMBER OF
HORMONES INCLUING 2 TERROIDS
THAT WILL BE FOCUSING ON,
ESTRADISCIPLINARYOLE AND
PROJECTOR OWN AS WELL AS SOME
KIND OF SMALL PROTEIN MOLECULES,
THE INHIB THORSINS AND THE
FOLLICLE STATINS, AND THE INHIB
THORSINS, FEEDBACK AND
ININCREASE IN BODY HIT AT THE
LEVEL OF THE PITUE TARY.
AND AS WHAT HAPPENED IN THE
MENOPAUSE AS ESTROGEN AND
PROGESTERONE LEVELS FALL, INHIB
THORSIN LEVELS DECREASE AND THAT
REMOVES LH AND FSH WHICH ARE
EVENTUALLY TONICALLY ELEVATED.
SO THOSE ARE SOME OF THE MARKERS
OF THE PERO MENOPAUSE WE HAVE
INCLUED.
THIS IS AN OLD SCHEMATIC JUST
SHOWING THE DIFFERENCES IN THE
ESTRA-DIAL AND PROGESTERONE
DIALSA THE LEVEL, AND THE
TROAPINS AT THE LOWER PANEL, AT
3 PHASES OF REPRODUCTIVE LIFE,
DURING THE NORMAL REPRODUCTIVE
LIFE CYCLE, THEN POST MENOPAUSE
AND THEN THE TRANSITION FROM
HERE TO HERE WHICH IS VARIABLY
CALLED THE MENOPAUSE TRANSITION
OR THE PERIMENOPAUSE, DURING THE
COURSE OF THE NORMAL CYCLE,
ESTRADISCIPLINARYOLE HAS THE BI
PHASIC PATTERN OF SECRETION, AND
SECRETION IS LARGELY CONFINED TO
THE LUTEAL PHASE OF THE
MENSTRUAL CYCLE.
FSH INITIALLY INCREASES WHEN THE
INIT FOLLICLE IS RECRUITED
DURING THE EARLY FOLLICULAR
PHASE AND BOTH HAVE PEAKS AROUND
OUR APPROXIMATE TO OFULATION,
DURING POST MENOPAUSE, ESTROIEN
AND MENOPAUSE LEVELS ARE
CONSISTENTLY LOW, WHEREAS FSH
AND LH ARE TONICALLY ELEVATED
AND YOU STOP SEEING THE
PRODUCTION OF THESE HORMONES.
THE TRANSITION IS QUITE A
VARIABLE PERIOD, THERE ARE FEWER
OFLATTORY CYCLES,
ESTRADISCIPLINARYOLE LEVELS IN
THE MAIORITY OF WOMEN BUT NOT
ALL ARE ACTUALLY LOWER
PROGRESSIVELY LOWER WITH KIND OF
AN INCREASED DECLINE DURING THE
LATE MENOPAUSE TRANSITION, FEWER
OVULATTORY CYCLES FOR LESS
PROGESTERONE.
THE ELEVATED FSH LEVEL WAS 1
MARKER THAT USED TO BE
CONSIDERED AS PART OF SOME OF
THE EARLY DEMONSTRATIONS OF
RELATED TO A WOMAN'S
REPRODUCTIVE AGING USED IN
FERTILITY CLINICS AS WELL, WHERE
SOME OF THE CRITERIA THAT WE'RE
DEVELOPED TO IDENTIFY THE
PERIMENOPAUSE EMPLOY THESE
CRITERIA HAVE BEEN FORMALIZED IN
THE STAGES OF REPRODUCTIVE AGING
WORKSHOP AND SO THE MENOPAUSE
TRANSITION WHICH IS THE TIME
FROM REPRODUCTIVE TO THE POST
MENOPAUSE IS CHARACTERIZED BY
VARIABLE CYCLELING, SKIPPED
PERIODS, OVER ALL AN ELEVATED
FSH LEVELS AND THE PERIMENOPAUSE
HAS BEEN DEFEIGNED AS THAT
PERIOD OF THE TRANSITION PLUS
THE FIRST YEAR AFTER THE LAST
MENSTRUAL PERIOD.
SO THIS REALLY KIND OF
CHARACTERIZES THE ROLLER COASTER
OF ENDOCRINE EVENTS THAT OCCUR
DURING THE MENOPAUSE TRANSITION,
AND THAT'S WHAT WE'RE FOCUSING
ON ON IN OUR STUDIES RELATED TO
DEPRESSION.
SO, JUST AS A BACKGROUND, THE
MENOPAUSE TRANSITION PROBABLY IS
ABOUT--IT CAN LAST FROM ANYWHERE
FROM 1 YEAR OR SHORTER, LIKE THE
LAST NORMAL MENSTRUAL PERIOD
COULD BE THE LAST MENSTRUAL
PERIOD.
IN OTHER WOMEN IT MAY GO ON FOR
UP TO 15 YEARS.
SO IT'S QUITE VARIABLE, IT'S A
LOT OF INDIVIDUAL VARIATION FROM
CYCLE TO CYCLE AND ALSO FROM
WOMAN TO WOMAN.
SO AS WE SUGGESTED THERE'S
EPIDEMIOLOGIC EVIDENT TO
SUGGIEST THAT FOR SOME WOMEN
THIS, IS A PERIOD OF INCREASED
RISK OF DEPRESSION.
WHAT HASN'T BEEN ASKED IS
WHETHER THERE'S DIFFERENCES IN
REPRODUCTIVE FUNCTION THAT
EITHER INCREASE THE RISK FOR OR
ACCOMPANY PERIMENOPAUSAL
DEPRESSION.
OUR CROSS SECTIONAL STUDIES AND
THOSE OF SEVERAL OTHER PEOPLE
HAVE SHOWED THERE'S THOUGH
BONAFIDE ENDOCRINE OPATHY, NO
DEFICIENCY OR EXCESS OF ESTROGEN
OR PROGESTERONE THAT
DISTINGUISHES THESE WOMEN FROM
REPRODUCTION FOR AGE AND MATCHED
WOMAN WITHOUT DEPRESSION.
AND THERE'S NO CHARACTERISTIC,
INCLUDING HOT FLASHES THAT SEEM
TO DISTINGUISH THIS GROUP.
SO WE ASKED THE QUESTION IN OUR
LONGITUDINAL STUDY, THIS IS DONE
BY CONSTANT ZAO, A CLINICAL
FELLOW IN THE BEHAVIORIAL
ENDOKRENNOLOGY BRANCH AND SHE'S
ANALYZED THIS DATA IN WHICH WE
FOLLOWED PREMENOPAUSAL HEALTHY
A-SYMPTOMATIC WOMEN, EVERY 6-8
MONTHS, WE CONDUCTED VISITS
DURING THE EARLY FOLLICULAR
PHASE OF THE CYCLE UNTIL NAY
WERE 6-12 MONTHS AFTER THE LAST
MENSTRUAL PERIOD AND THIS WAS
KIND OF A BEAR OF A STUDY.
WE DID BLOOD HORMONE MEASURES
AND I WILL BE FOCUSING ON FSH
AND ESTRADISCIPLINARYOLE, AND
PRELIMINARY DATA THAT CONSTANCE
HAS ON THAT, AND PERFORMED
DIAGNOSTIC INTERVIEWS IN ORDER
TO EITHER CONFIRM THE PRESENCE
OR ABSENCE OF THE DIN DROAM OF
DEPRESSION AND IN SOME CASES
BECAUSE IT'S PERSPECTIVELY
MONITORED, THESE WOULD BE MINOR
DEPRESSIONS, WE HAVE DAILY
SYMPTOM RATINGS AS WELL AS
CLINIC VISITS SO WE CAN
UNDERSTAND THE PRODROAM.
WE ALSO INCLAUDED A VARIETY OF
MEASURES THAT HAD BEEN EITHER
REPORTED TO ACCOMPANY DEPRESSION
DURING MIDLIFE OR THE
PERIMENOPAUSE AS WELL AS EVENTS
THAT MIGHT CONTRIBUTE TO THE
ONSET OF DEPRESSION.
SO THIS IS A SPAGHETTI GRAPH OF
THE 89 WOMEN WHO HAVE BEEN IN
THIS STUDY THAT CONSTANCE IS
ANALYZING, THE Y AXIS SHOWS THE
NUMBER OF PARTICIPANTS.
THE X-AXIS, THE LAST MENSTRUAL
PERIOD IS MARKED BY THE DARK
LINE.
THE TIME BEFORE THAT ARE THE
YEARS PRIOR TO THE LAST
MENSTRUAL PERIOD AND THEN AFTER
THAT ARE THE YEARS AFTER THE
LAST MENSTRUAL PERIOD.
EACH LINE WEP RESENTS A WOMEN'S
COURSE THROUGH THE STUDY AND
EACH DOTS REPRESENTS INDIVIDUAL
CLINIC VISITS SO ON AVERAGE WE
FOLLOWED EACH WOMAN FOR
APPROXIMATELY 6 YEARS BUT
CONSIDERABLY RAINCHL FROM 1-12.6
YEARS, JUST TO FOCUS ON THE RED
DOTS ARE THE WOMEN WHO REMAIN
ASYMPTOMATIC DURING THE TRIAL
AND BLUE DOTS ARE FOR THOSE WHO
DEVELOP DEPRESSION AND WHEN WE
FOUND IS A CLUSTERING OF
DEPRESSIVE EPISODES.
THESE ARE ALL THE EPISEDENTARYS
OF DEPRESSION THAT OCCUR DURING
THE TRIAL IN EACH OF THESE
WOMEN.
AND THERE WAS A CLUSTERING, THE
Y-AXIS IS THE NUMBER OF
DEPRESSIVE EPISODES IN THE
AGAIN, IT'S PREAND POST LAST
MENS, AND THIS IS OCCURRING
DURING THE 24 MONTHS SURROUNDING
THE LAST MENSTRUAL PERIOD AS
WELL AS EPISODES THAT OCCURRED
PRIOR TO THAT BUT WHAT WERE
HIGHLIGHTED IN PINK ARE THE 1S
THAT OCCURRED IN THE YEAR BEFORE
OR AFTER THE LAST MENSTRUAL
PERIOD.
AND WE IDENTIFIED 29 EPISODES IN
22 WOMEN.
WENT OF THESE OCCURRED IN THE 24
MONTHS SURROUNDING THE LAST
MENSTRUAL PERIOD AS A MENTIONED.
IN 19 OF THESE 20 WOMEN THAT
EVEN IF THEY DIDN'T OCCUR DURING
THAT PERIOD OF THE 2 YEARS
AROUND LAST MENSTRUAL PERIOD,
THE EPISODE OF DEPRESSION
OCCURRED AFTER WE IDENTIFIED AND
ELVITTED PLASMA FSH LEVELS
SUGGIESTING THAT THE
REPRODUCKIVE AGING PROCESS
PRESEED THE ONSET OF THE
DEPRESSION.
FINALLY, ONLY 4 WOMEN IN THIS
COHORT HAD A PREVIOUS PATH MAJOR
DEPRESSION, SO 18 OF THESE 22,
WOMEN HAD A FIRST ONSET OF
DEPRESSION IN THE PERIMENOPAUSE.
SO LOOKING AT THEIR PLASMA
ESTRADISCIPLINARYOLE LEVELS
SHOWN IN THIS GRAPH AND I
APOLOGIZE, THERE'S POTENTIAL
CONFUSION WHERE THAL CASE, THE
BLUE LINE ARE THE WOMEN WHO DID
NOT EXPERIENCE DEPRESSION, SO
THESE ARE--THESE ARE THE
ASYMPTOMATEC WOMEN, THE RED LINE
IS IN THIS CASE, THE WOMEN WHO
DID DEVELOP DEPRESSION AND THIS
SHOWS THE PATTERN OF
ESTRADISCIPLINARYOLE SECRETION
ALONG WITH 95% CONFIDENCE
INTERVAL BAN OVER THE COURSE OF
THE STUDY AND IT'S ANCHORED
RELATIVE TO THE LAST MENSTRUAL
PERIOD.
AND WHAT WE FOUND IS SIGNIFICANT
THESE PRELIMINARY DATA
SUGGESTING IGF 95 CANT EFFECTS
INTERACTION BETWEEN TIME AND THE
ONSET OF DEPRESSION AND THAT
THESE WERE DEMON TRAITED WITH
THE WOMEN WHO DEVELOPED
DEPRESSION HAD AN EARLIER PEAK
DURING THE MENOPAUSE TRANSITION
AND A HIGHER LEVEL OF
ESTRADISCIPLINARYOLE SECRETION
COMPARED WITH THE CONTROLS WHO
PEAKED APPROXIMATELY A YEAR
LATER.
THIS IS HAPPENING, AGAIN,
THOUGH, APPROXIMATELY 5-6 YEARS
WHEREAS WE'RE SEEING THE
CLUSTERING OF DEPRESSIVE
EPISODES IN THE YEAR OR SO AFTER
THE LAST MENSTRUAL PERIOD, SO
THESE ARE THINGS THAT ARE
HAPPENING BEFORE HAND THAT WE
WOULDN'T CAPTURE IN OUR CLINIC
WHEN WE'RE EVALUATING WOMEN
CROSS SECTIONALLY.
THE 2 LINES MEET ABOUT A YEAR
BEFORE THE FINAL MENSTRUAL
PERIOD AND BEGAN TO SEPARATE.
SO THESE DATA SUGGEST A MORE
EARLIER PEAK AND A MORE RAPID
DECLINE OF ESTRADISCIPLINARYOLE
IN THE WOMEN WHO DEVELOP
DEPRESSION DURING THE
PERIMENOPAUSE, THE FSH LEVELS
SHOWING THE SAME SET UP WITH THE
FSH, LEVELS AND THE 95%
CONFIDENCE BANS FOR THE
DEPRESSED WOMEN IN RED AND THE
IEE, AUDIENCE SYMPTOMATIC WOMEN
IN BLUE, THAT AGAIN, WE FOUND
SIGNIFICANT EFFECTS OF
INTERACTIONS BETWEEN TIME AND
THE DIAGNOSIS OF DEPRESSION
WHERE THERE WERE HIGHER FSH
LEVELS, VERY EARLY ON IN THE
MENOPAUSE TRANSITION, IN THE
WOMEN WHO DEVELOP DEPRESSION AS
WELL AS A STEEPER PEEK INCREASE
THAT MAY CORRESPOND WITH THE
MORE STEEPER DECLINE OF
ESTRADISCIPLINARYOLE, REMEMBER
THESE 2 HORMONES ARE KIND OF IN
A LITTLE BIT OF A RECIPROCAL
RELATIONSHIP WITH EACH OTHER
PRIOR TO THE LAST MENSTRUAL
PERIOD.
SO, THESE DATA SUGGEST THAT ARE
MAY ACTUALLY BE SOME HORMONAL
ANTISEEDENTS OR ACCOMPANIMENTS
OF PERIMENOPAUSAL DEPRESSION BUT
MOST OF THEM ARE OCCURRING
BEFORE THE ONSET OF DEPRESSION.
SO THIS MAY BE SOMETHING THAT WE
CAN, IF CONFIRMED IN THE FINAL
DATA, MAY GIVE US SOME MEASURE
OF WHAT MIGHT BE HAPPENING PRIOR
TO I WOMAN EXPERIENCING
DEPRESSION DURING THE MENOPAUSE
TRANSITION THAT WILL GIVE US
SOME MARKERS OF RISK.
SO GOING BACK TO WHAT WE TALKED
ABOUT, IS THAT THE MENOPAUSE
TRANSITION, WE SEE THE EPISODES
CLUSTER DURING THE LATE
TRANSITION WHICH IS A TAME AS
WELL AS SEVERAL OTHER STUDIES
SHOWING THIS, THAT IT'S A TIME
OF KIND OF THE MOST--THE
GREATEST DECLINES IN ESTRO
DISCIPLINARYOLE LEVEL.
WE ALSO KNOW FROM SEVERAL
STUDIES THAT
ESTRADISCIPLINARYOLE MAY HAVE
BOTH ACUTE ANTIDEPRESS ABT LIKE
EFFECTS AS WELL AS PREVENTATIVE
PERIMENOPAUSAL DEPRESSION
SYMPTOMS AACCORDING TO A STUDY
BY JENNIFER GORDON.
SO WE ASKED WHETHER THIS
PRECIPITATES DEPRESSION IN WOMEN
WITH A HISTORY OF PAST
DEPRESSION?
SO THOSE WOMEN WE KNOW ARE
VULNERABLE TO DEVELOPING
DEPRESSION, WHAT ARE THE EFFECTS
ON MOOD COMPARED TO WOMEN WHO
DID NOT DEVELOP A DEPRESSION, SO
THIS IS THE SCHEMATIC DESIGN OF
THAT STUDY, WE RECRUITED WOMEN
WHO HAD REPORTED ON HOW TO WELL
CHARACTERIZE DEPRESSION DURING
THE PERIMENOPAUSE.
THEY WERE NOW POST MENOPAUSE AND
HAD A REMISSION OF THE
DEPRESSION OR IT STARTED SOME
FORM OF THERAPY.
THEY WERE TAKEN OFF THEIR
CURRENT MEDS AND PLACED ON A
STANDARD LEVEL OF
ESTRADISCIPLINARYOLE AND A
HUNDRED MICROGRAMS A DAY GIVEN
BY SKIN PATCH FOR 3 WEEKS.
AFTER 3 WEEKS, HALF THE GROUP
CONTINUED ON THE SAME DOSE OF
ESTRADISCIPLINARYOLE, WHAZ THE
OTHER HALF OF THE WOMEN WERE
CROSS TD OVER TO PLACEBO
PATCHES.
SO IF THERE WAS GOING TO BE
EVIDENCE OF.
--SO THEY EXPERIENCED BOTH THE
SAME DOSES OF ESTRADIOL,
PRESUMABLY HAD A CHANGE IN
HORMONE MOANS IN THE 1 WHO IS
WENT THROUGH THE WITHDRAWAL
EMPLOY THIS IS AN EXAMPLE OF THE
RESULTS WE SAW, THIS IS SCORES
ON THE Y-AXIS OR THE CENTERS FOR
EPIDEMIOLOGIC DEPRESSION STUDY
SCALE WHERE HIGHER SCORES
REPRESENT MORE SEVERE DEPRESSIVE
SYMPTOMS.
Y-AXIS EACH OF THESE BARS
REPRESENT THE AVERAGE SCORE IN
THE WOMEN WHO WERE IN THAT GROUP
FOR EACH OF THEIR CLINIC VISITS
DURING THE 6 WEEKS OF THE TRIAL.
FOCUSING ON THE GROUP IN THE
MIDDLE, THESE ARE THE WOMEN WITH
PAST PERIMENOPAUSAL DEPRESSION
WHO WHEN THEY WITHDREW
EXPERIENCED RECURRENCE OF
SYMPTOMS, IN CONTRAST TO THESE
WOMEN WHO CONTINUE OFFICE OF
DIVERSITY ESTRADISCIPLINARY
OLDER PEOPLE BUT HAD THE SAME
PAST HISTORY BUT COMPEARED TO
THE CONTROL WOMEN WHEN
EXPERIENCED NO SUBSTANTIAL
CHANGE IN MOOD WHEN THEY
UNDERWENT AN IDENTICAL HORMONE
WITHDRAWAL.
SO THESE DATA DOCUMENT THIS
DIFFERENTIAL SENSITIVITY WE TALK
ABOUT WHERE AND OTHERWISE IESHES
DENTICAL CHANGE IN HORMONE WILL
HAVE THE KASP A R PASQUANTINOITY
OF INDUCING NEG5 MOOD STATES IN
SOME WOMEN WHEN ARE OTHERWISE
VULNERABILITY BUT NOT THE
MAJORITY OF WOMEN.
WE'RE PURSUING THIS QUESTION NOW
IN A TRIAL, ASK WHETHER THE
ASHINGS OF ESTROGEN WITHDRAWAL
ARE MEDIATED BY E. R. BETA.
SO WHY E. R. BETA.
THIS WAS A SECOND ESTRAGENERATED
THAT WAS CLONED BY CANNED WHAT,
AND [INDISCERNIBLEA IN 1996 AT
THE [INDISCERNIBLE].
AND IT'S ENCODED ON A SEPARATE
CHROMOSOME THAN THE ORIGINAL
ER-ALPHA CHROMOSOME 6 AND 14
RESPECTIVELY WITH 6 BEING FOR
ER-ALPHA AND 14 FOR ER-BETA.
SO THEY MAY BE UNDER DIFFERENT
EVOLUTIONARY PRESSURES EMPLOY
WHAT ER BETA IS OF INTEREST
STHAT IT SEEMS TO BE MORE
RELEVANT FOR SOME OF THE BRAIN
AFFECTS THAT WE'RE LOOKING AT
AND IT IS KIND DIFREPRESENTIALLY
LOCALIZED IN THE BRAIN AND
PREFRONTAL CORTEX, TEMPORAL
LOBES, IT ALSO, IN AN STUDIES
HAVE BEEN SHOWN TO MODEIATE THE
EFFECTS OF ESTRADIOL ON A RANGE
OF AFFECTIVE LIKE BEHAVIORS AS
WELL AS REGULATING THE STRESS
RESPONSE IN PARTICULARLY HPA
ACCESS FUNCTION.
SO WHEN WE THOUGHT WAS WHETHER
WE KNOW THAT ER ALPHA PREVENTS
THE WITHDRAWAL EFFECTS, WHAT WE
WANT TO LOOK AT IS WHETHER
SCHECT OFLY ER BETA MAY PREVENT
THESE BECAUSE 1 OF THE THINGS IS
SINCE THE WOMEN'S HEALTH
INITIATIVE, THERE HAS BEEN A
CONCERN AMONGST WOMEN AND THEIR
GYNECOLOGISTS ABOUT USING
ESTROGEN THERAPY ALTHOUGH THAT
PENDULUM IS SWINGING BACK
SOMEWHAT BUT CERTAINLY ER BETA
COULD AFFORD A MORE TARGETED
THERAPY ON SOME OF THE BRAIN
CONDITIONS THAT WE'RE LOOKING AT
WHETHER IT'S MOOD OR COGNITION,A
WELL BECAUSE OF ITS LACK OF
EFFECTS ON THE ENDOMETRIUM, ER
BETA MAY HAVE A LONGER TERM
SAFETY PROFILE THAN TYPICAL
ESTROGEN THERAPY.
SO THIS STUDY UNFORTUNATELY OR
FORTUNATELY IS ALMOST FINERBED
BUT NOT FINISHED AS OF YET.
WE HAVE ABOUT 5 MORE WOMEN TO
RECRUIT FOR THIS STUDY AND WHAT
WE DO IS WE RECRUIT WOMEN
SIMILAR TO THE ESTROGEN
WITHDRAWAL STUDY.
THEY ARE PLACED ON A STANDARD
DOSE OF ESTRADIOL AND AFTER 3
WEEKS, A THIRD OF THEM ARE
CROSSED OVER TO PLACEBO WHICH
WOULD BE THE WITHDRAWAL PERIOD
AND THEN THE OTHER 2/3RDS
RECEIVE 1 OF 2 DOSES OF THIS
LYINTAIZ COMPOUND WHICH IS THE
ESTROGEN RECEPTOR BETA AGONIST.
WE USE 2 DIFFERENT DOSES TO BOTH
LOOK AT IMPACT AND INCREASED
PENETRATION TO THE BRAIN WHERE
THAT'S BEEN A PROBLEM FOR SOME
OF THE PREVIOUS ESTROGEN
RECEPTOR AGONIST, IT COMPLICATES
THINGS A LITTLE BIT BECAUSE THE
OPTIMAL DOSE FOR SELECTIVITY FOR
ER BETA VERSUS ER ALPHA IS AT
LOWER DOSES SO WE HAVE TO
INCLUDE A NUMBER OF THINGS WE'RE
DOING IN COLLABORATION WITH ALAN
[INDISCERNIBLE] TO MONITOR
ER-ALPHA FEESKTS IN THESE WOMEN,
SO WE CAN BE CERTAIN THAT WE CAN
SAY PREDOMINANTLY, AND WHAT WE
HAVE SEEN, IS THAT IN SOME OF
OUR WOMEN, WE HAVE BEEN ABLE TO
REPLICATE THE ESTRO GENERATED
WITHDRAWAL.
THESE ARE CSD SCORES SO THIS
WOMEN FOR EXAMPLE, WHO MAY OR
MAY NOT HAVE BEEN ON PLACEBO,
BUT REGARDLESS, SHE DID
EXPERIENCE A RECURRENCE OF HER
MOOD SYMPTOMS OR IN THE CONTEXT
OF THE DOUBLE BLIND.
SO WE ARE AT LEAST ABLE TO DO
THE--OR REPLICATE THE SIGNAL AND
WE'RE HOPING NOW TO SEE THAT IN
A COUPLE MONTHS WHAT THE EFFECTS
OF ER-BETA MAY OR MAY NOT BE.
SO IN THE LAST PART OF MY TALK I
WANT TO FOCUS ON SOME OF OUR
INVITRO STUDIES WE HAVE DONE TO
ASK THE QUESTION ABOUT WHAT
GIVES WITH THE DIFFERENCE
BETWEEN THE WOMEN WITH PAST
PERIMENOPAUSAL DEPRESSION WHO
EXPERIENCE RECURRENCE AND THE
CONTROLS WHO ARE OTHERWISE
IDENTICAL EXCEPT THEY DID NOT
HAVE A HISTORY OF DEPRESSION
EITHER DURING THE PERIMENOPAUSE
OR AT ANY OTHER TIME IN THEIR
LIFE, SO THIS IS WORK THAT'S
DONE IN COLLABORATION, THIS IS
WORK DONE BY SARAH
[INDISCERNIBLE], A FELLOW IN OUR
GROUP AS WELL AS IN
COLLABORATION WITH DAVID GOLDMAN
AT THE LAB OF NEUROGENETICS AT
NIAAA.
AND WHAT WE WANTED TO ASK WAS
GIVEN THAT STEROIDS ACT THROUGH
THE NUCLEAR MEMORY RESPONSE
BREAN IN LARGE PART IS WHETHER
THERE'S A DRVES IN THE CELLULAR
MECHANISM UNDERLYING THIS
DIFFERENTIAL BEHAVIOR RESPONSE
TO ESTROGEN WITHDRAWAL.
SO WHAT SARAH DID WAS TRY TO
RECAPITULATE THE CLINICAL SPRMS
THAT WE'RE DOING IN THESE WOMEN
BY TAKING CELLS FROM THEM AND
TRYING TO EXPOSE THEM TO
ESTROGEN OR ESTROGEN WITHDRAWAL.
SO WE RECRUITED IN THE FIRST
COHORT, WE RECRUITED WOMEN WHO
WERE SERVED AS CONTROLS IN THE
ESTARE GEN WITHDRAWAL STUDY, OR
WERE IN THE PERIMENOPAUSAL
DEPRESSION GROUP, AND WHO SHOWED
THE PHENOTYPE OF A RECURRENCE OF
THEIR MOOD SYMPTOMS DURING
ESTROGEN WITHDRAWAL.
NOW THE FIRST QUESTION WAS TO
SEE SARAH DID PATIENT DERIVED
LYMPHBLASTOID CELL LINES THAT
ARE EPSTEIN BARR-INFECKED AND
THEY ARE KIND OF OLD LYMPHOCYTES
TO THE A LOT OF THE INITIAL
METHYLATION MARKS AND MARKERS
RELATED TO ENVIRONMENT OR OTHER
FACTORS ARE WASHED OUT AND
THERE'S JUST LEFT THE GENETIC
CONSTITUENTS AND WE WANTED TO
SEE WHETHER THESE CELLS ACTUALLY
HAD THE MACHINERY TO COMMUNICATE
WITH SEX STEROIDS SO WE
DID--SARAH SHOWED THAT
THESE--MOST OF THE SEX STEROID
RECEPTORS WERE PRESENT BOTH IN
MESSAGE AND IN PROTEIN.
SO, THEN WHAT WHEY DID IS SHE
SET UP EACH CELL LINE, WOULD BE
EXPOSED TO A VEHICLE, I THINK
JUST AS THE CONTROL ESTRADIOL
EXPOSURE IN THE CELL SCULTURE OR
ESTRA-DIAL EXPOSURE FOLLOWED BY
CHANGE TO VEHICLE WHICH WOULD BE
THE ESTRADIOL CONTROL GROUP ASK
WE DID THAT WITH BOTH THE
CONTROLS AS WELL ASLET
PERIMENOPAUSAL GROUP.
AND THEN WE HAD A SMALL COHORT
WHICH WAS RECRUITED ABOUT YOU
HAD A PHENOTYPE, SHE PERFORMED
WHOLE TRANSCRIPTOME SEQUENCING
AS WELL AS DIFFERENTIAL GENE
EXPRESSION AND A PATHWAY NETWORK
ANALYSIS.
IN THE SECOND COHORT WHICH WAS A
BROADER COHORT I THINK OF 18
WOMEN WHO MET CRITERIA FOR
MENOPAUSAL DEPRESSION AND 21
CONTROLS WHO DID FOCUS ON THE
HAVE PERIMENOPAUSAL DEPRESSION,
SHE USED A DIFFERENT TECHNIQUE
TO CONFIRM THE GENE EXPRESSION
IN THAT GROUP.
SO 2 GENES APPEAR THAD WERE OF
BIOLOGICAL INTEREST THAT WERE
ALSO KIND OF SEX STEROID
RELATED, WERE SIGNIFICANT,
DIFFERENT BETWEEN CONTROLS AND
PATIENTS AND THAT HAD SOME
POETIC TEBTIAL RELEVANCE FOR
AFFECTIVE SYNDROMES.
ONE OF THEM IS CXCL 10 WHICH IS
A CHEMOKINE.
PROINFLMATORY.
IT'S ALSO CALLED IP 10, AND
WHAT'S INTERESTING GIVEN OUR
KIND OF EPIDEMIOLOGIC STUDIES
THAT DISASSOCIATION BETWEEN
HEART DEC AND DEPRESSION DURING
PERIAND POST MENOPAUSE THAT IT
HAS BEEN IDENTIFIED BY THE
CLINICAL BIOMARKER FOR HEART
FAILURE AND LEFT VENTRICULAR
DYSFUNCTION.
AGAIN IT IS POTENTIALLY OF
INTEREST GIIVE THIS
EPIDEMIOLOGIC FINDINGS OF THE
INCREASED CARDIAC MORTALITY IN
PERIMENOPAUSAL DEPRESSION EMPLOY
SO WHAT SARAH FOUND IS THE HOT
OR WHY-AXIS OF THESE KILOBASE, I
CAN'T REMEMBER THE M BUT IF YOU
NEED TO KNOW I CAN ASK SARAH,
THAT SHE FOUND THAT YOU KNOW A
HIGHER EXPRESSION IS ASSOCIATED
WITH THE HIGHER VALUEOT Y-AXIS,
AND THESE ARE THE CONTROL
VALUES, DURING THE 3 HORMONE
CONDITIONS AND THESE ARE THE
VALUES FOR THE WOMEN WITH
PERIMENOPAUSAL DEPRESSION AND
YOU SEE DURING THE ESTRADIOL
WITHDRAWAL PHASE, THIS HISTOGRAM
HERE THAT THERE WAS A
SIGNIFICANT INCREASE IN THE
EXPRESSION FOR THE YEEN FOR CXCL
10.
SHE THEN USED IN THE SECOND
COHORT, A LARGER COHORT WITH A
BROADER FEIGNY TYPE, SHE USED PC
R TO CONFIRM THE INCREASED
EXPRESSION OF CXCL 10 AND SHE
ALSO LOOKED TO SEA WHETHER THERE
WAS AN INCREASED EXPRESSION IN
THE CXCL 10 PROTEIN USING AN
ELIZA ASSAY WHICH SHOWED IN THE
MEDIA OF THESE CELLS, NOT IN THE
CONTROLS BUT IN THE PATES, THERE
WAS INCREASED EXPRESSION OF THE
PROTEIN EMPLOY SO THAT'S
SOMETHING WE'RE GOING TO LOOK
FURRINGER IN OUR STUDY IN OUR
LONGITUDINAL STUDY, THE SECOND
YEEN WAS A YEEN THAT ENCODES THE
CYTOCHROME P457 B 1 STEROID
METABOLIC HORMONE, ACTUALLY
INVOLVED IN THE METABOLISM OF
PREGMEANA LEAN AND DATA, IT'S
THE MAJOR ROOT FOR THE EXCRETION
OF THESE 2 HORMONES BOTH OF
WHICH ARE MIEWR O STEROIDS AND
IT IS INTERESTING THAT 7 HYDROXY
EHDA IS A BETA AGONIST SO THE
INCREASE IN THAT COULD REFLECT
SOME TYPE OF HOMEOSTATIC
MECHANISM IN WOMEN WITH
PERIMENOPAUSAL DEPRESSION EMPLOY
WHAT WE FOUND HERE AGAIN,
SIMILAR CONSTRUCT TO THE SLIDE,
IN THE WOMEN WITH PERIMENOPAUSAL
DEPRESSION ACROSS ALL 3 HORMONE
CONDITIONS SO THIS IS MORE OF A
STRAIGHT MARKER RATHER THAN
SOMETHING RELATED TO ESTROGEN
WITHDRAWAL THAT THERE WAS AN
INCREASED EXPRESSION OF THIS
GENE.
THAT WAS CONFIRMED IN THE
BROADER PHENOTYPE BY PC R, AND
THAT ALSO WHEN WE TOOK--ADD THE
HORMONE LEVELS FOR THE WOMEN
THAT PARTICIPATE INDEED THIS
STUDY, IN THE LARGER PHENOTYPE,
THAT THE EXPRESSION OF THIS GENE
CORRELATED WITH DHEA LEVELS IN
THOSE WOMEN.
SO AGAIN IT'S GOT BIOLOGICAL
RELEVANCE AND WE HOPE TO BE
LOOKING AT IN CONSTANTS THE
LONGITUDINAL STUDY, BOTH THE
CHANGE IN THESE INFLAMMATORY
MARKERSA WELL AS THESE HORMONES
THAT MIGHT BE ALTERED BY AN
ALERATION IN THE SIP 7 B1.
SO IN SUMMARY THEN, THESE DATA
SUGGEST THAT INCREASED CXCL10
BEING BE A RISK FACTOR FOR BOTH
PERIMENOPAUSAL DEPRESSION AND
CARDIOVASCULAR DISEASE
CONSISTENT WITH JENNIFER
GLORDON'S WORK SHOWING THAT IT
PREVENTED PERIMENOPAUSAL
DEPRESSION AND PREVENTED HEART
DISEASE ALTHOUGH THIS IS
CONTROVERSIAL.
IT ALSO COULD SUGGIEST THAT THE
BENEFITS OF ESTRADIOL THERAPY
FOR DEPRESSION AND
CARDIOVASCULAR INDICATIONS IN
SOME WOMEN, AGAIN THIS, IS A
SUBGROUP OF WOMEN, THE MAJORITY
OF WOMEN GO THROUGH
PERIMENOPAUSE WITHOUT ANY
EPISODES OF DEPRESSION BUT IT
COULD SERVE AS 1 POTENTIAL
EXPLANATION ALTHOUGH THERE ARE
MANY FOR THE DISCORDANT
RESULTINGS FOR OBSERVATIONAL
STUDIES LOOKINGA THE HORMONE
EFFECTS OF THERAPY IN WOMEN AND
NEGATIVE FINDINGS OF THE
WEMENT'S HEALTH INITIATIVE.
FINALLY IT SUGGESTS THAT THE
ROLE OF NEUROSTEROIDS IN
PERIMENOPAUSAL DEPRESSION AND
THERE IS 1 TRIAL ONGOING DOWN AT
THE UNIVERSITY OF SOUTHWEST IN
TEXAS LOOKINGA THE EFFECTS OF
PREGNENOLONE AS A TREME FOR
THESE WOMEN.
IF I HAVE A FEW MINUTES WHICH I
DO, I WANT TO GO THROUGH
PRELIMINARY OTHERWISE LESS
VETTED MATERIAL THAT
DR. [INDISCERNIBLE] HAS FOUND
RECENTLY.
AND WHAT SHE DID WAS EMPLOY A
DATA-DRIVEN APPROACH RATHER THAN
LITERATURE BASED ON APPROACH TO
LOOKING AT KIND OF GENE NETWORKS
AND HUB YEENS THAT MAY ALSO BE
RELEVANT IN PERIMENOPAUSAL
DEPRESSION AND THIS IS A CLUSTER
DENDRITIC CELL ROUGH ATOM GRAM
WHICH SHOWS DRVESS IN GENE
EXPRESSION THAT ARE HIGHLY
CORRELATED WITH EACH OTHER, AND
THEY THEN DEFINE THESE CLUSTERS
OF OTHERWISE CORRELATED GENES
AND WE'LL FIND IN THE MOST
HEAVILY CORRELATED GENE HUB OR A
HUB FOR THAT CLUSTER.
AND THEN THESE ARE THEN
PROCESSED WITH RESPECT TO THEIR
CORRELATIONS IN A VERY LARGE
MATRIX, MULTIPLE MATRIXES
SIMILAR TO WHAT'S BEEN DONE IN
THE BRAIN IMAGING STUDIES WITH
RESTINGITATE TO IDENTIFY
DIFFERENCES EITHER BETWEEN
PATIENTS AND CONTROLS OR BETWEEN
KIND OF ESTRO GENERATED
WITHDRAWAL AND ESTRO GENERATED
THERAPY AND THEN THOSE DEFENSES
ARE MAPPED ON TO BASED ON
LITERATURE OF KIND OF AREAS OF
GENE EXPRESSION THAT ARE
RELEVANT FOR A VARIETY OF
BIOLOGICAL PROCESSES, AND WHAT
SARAH HAS DONE THEN WITH THIS
DATA DRIVEN APPROACH IS
IDENTIFIED SEVERAL MODULES THAT
ARE RELEVANT FOR EITHER ESTROGEN
WITHDRAWAL OR FOR PERIMENOPAUSAL
DEPRESSION AND 1 OF THEM IS
RELATED TO THIS MIDNIGHT BLUE
MODULE WHICH IS WHEN WE LOOK AT
IT, IS 1 OF THE HUB GENES IS THE
PER 1 GENE WHICH MANY OF YOU
KNOW IS VERY RELEVANT FOR
GENERATING CIRCADIAN RHYTHMS, IT
MAY SPEAK TO SOME OF THE SLEEP
ISSUES THAT ARE PRESENT AND HAVE
BEEN IDENTIFIED DURING THE
PERIMENOPAUSE OR IN THE CONTEXT
OF PERIMENOPAUSAL DEPRESSION AND
ALSO MAY HELP US GIVE US A CLUE
AS TO WHAT MIGHT BE UNDERLYING
SOME OF THESE OR PUT AT A RISK
FACTOR FOR SOME OF THESE
CONDITIONS.
A SECOND GENE IS IN THIS OTHER
MODULE, THE DARK ORANGE WHICH
CONTAINS THE HUB GENE FOR
CXCL10, THE CYTOKINE I TALKED
ABOUT THAT SHE HAD IDENTIFIED
EARLIER BUT ALSO WHEN SARAH
COMPARED THIS WITH THE UK
BIOBANK THAT IT KIND OF
OVERLAPPED WITH WITH STUDIES IN
WOMEN WITH AN EARLIER AGENT OF
MENOPAUSE AND I KNOW THIS' A
CURRENT STUDY, HOWARD LEE IS
LOOKING AT THIS DATA IN WOMEN
WITH PREMATURE OVARIAN
INSUFFICIENCY, THERE HAS BEEN IN
THE LITERATURE ON PERIMENOPAUSAL
DEPRESSION, A LINK BETWEEN
PERHAPS AN EARLIER AGE OF
MENOPAUSE AND THE ONSET OF
DEPRESSION.
I ALWAYS INTERPRET IT AS A
POTENTIAL, THE EFFECTS OF STRESS
AND DEPRESSION THAT LED TO AN
EARLIER LOSS OF OVARIAN FUNCTION
BUT THIS DATA WE WOULD HAVE TO
KRE TINS CONSIDER THAT OR I
WOULD HAVE TO KRE TINS OCCUR
THAT AND IT MAY ACTUALLY BE AN
UNDERLYING RISK FOR BOTH
PERIMENOPAUSAL DEPRESSION AND AN
EARLIER ONSET OF THE MENOPAUSE
IN SOME WOMEN EMPLOY SO, OVERALL
THEN TO END, WE ARE WORKING ON
THIS TYPE OF STUDY DESIGNS AND
TO BETTER UNDERSTAND THE EFFORT
OF THESE BIOLOGY CONDITIONS DITD
UNDERSTANDING WHY IN SOME WOMEN
THIS SEEMS TO BE A NORMAL CHANGE
OF OVARIAN FUNCTION CAN TRIGGER
THIS MOOD STATE AND HOPEFULLY
THAT WILL DEVELOP NEW TREATMENTS
AND HAVE A DIFFERENT MORE
FOCUSED TARGET AND A DIFFERENT
SAFETY PROFILE IN ALL OF THESE
CONDITIONS AND HOPEFULLY SOME OF
OUR INVITRO STUDIES WILL
IDENTIFY MARKERS OF RISK OR
POTENTIALLY LEAD TO SOME
TREATMENTS THAT MAY BE MORE
NOVEL AND ALTERNATIVE AT LEAST
FOR WOMEN WITH THIS STANDARD
HORMONE THERAPY EMPLOY WITH THAT
IN MIND I WANT TO ACKNOWLEDGE
PEOPLE IN MY GROUP, SARAH
SPECTER, THE NURSE PRACTITIONER
IN THE GROUP, [INDISCERNIBLE]
WHO IS MORE FOCUSED ON OUR
PREMENSTRUAL DYSPHORIC STUDIES
BUT RUNS OUR LARGE CUMBERSOME
AND BEAR LIKE PUBERTY STUDY.
SARAH RUDZINSKAS, I MENTIONED,
AS WELL AS CONSTRANS ZAU, I WANT
TO MENTION PAUL WAKIM, WHILE HE
WAS HERE AND NOW XIAOBAI, LI,
WHO IS NOW FITTING US IN WITH
THEIR NORMAL DUTIES TO BE
STATISTICAL CONSULTANTS.
FINALLY SOME OF MY LONGEST
STANDING COLLABORATORS, KAREN
BERM AN AT NIH, LINNET NEEMAN
WHO HAS BEEN INVOLVED IN THESE
STUDIES, DAVID CANNED WHAT AT
UNC AND THEN DAVID GOLDMAN
RUNNING OUR COLLABORATION WITH
OUR MOLECULAR STUDIES SO WITH
THAT WE CAN, ALL 10 OF YOU CAN
CLAP.
[ APPLAUSE ]
NHI, I'M [INDISCERNIBLE] I'M A
NEW CLINICAL FELLOW FOR CARLOS
[INDISCERNIBLE], WE'RE STUDYING
RESISTANCE TO DEPRESSION AND
BIOMARKERS SO FAR HAVE BEEN
FOCUSED ON THE GLUTAMATE SYSTEM,
MY PROJECT IN THAT LAB, WE'RE
BEGINNING TO ELECTRIC AT
NEUROSTEROIDS AND MYSELF, VERY
INTERESTED IN NEUROPEPTIDE
SPECIFICALLY, VASE O SUPPRESS
EVALUATION PROCESS AND OXYTOCIN,
AND FROM THE LITERATURE REVIEW,
I'VE DONE SO FAR, IT SEEMS LIKE,
WELLOXYITOSEIN IS HARD TO
MEASURE AND ALSO KIND OF HARD TO
GIVE.
VASE O PRESS ANT IS VERY RELATED
TOOXYITOSEIN BUT LOOKING AT
THAT, AS AOXYITOSEIN AND
[INDISCERNIBLE] AS A YING AND
YANG SYSTEM, AND MY
UNDERSTANDING IS THERE'S A LOT
OF SEX DNCHS IN HOW IT AFFECTS
DEPRSESSIVE SYMPTOMS AMONG
OTHERS AND I'M WONDERING, DO YOU
HAVE ANY SUGGESTIONS ON LOOKING
AT THE INTERSECTION OF
NEUROSTERIES LIKE YOU'VE DONE
AND NEUROPEPTIDES AND IF YOU
HAVE ANY WHYEDS?
NYEAH, VERY GOOD QUESTION.
INTERESTING THAT YOU'RE WORKING
ON THAT.
YES, SO THERE ARE SEVERAL WELL
DOCUMMED SEX DIFFERENCES BOTH IN
TERMS OF THE WIRING AND THE IRPT
ACTIONS OF KIND OF NEUROSTEROIDS
AND PEPTIDES, WHEN I STAY
NEUROSTEROIDS, I SAY ESTROGEN IS
NEUROACTIVE AND MAY ACTUALLY BE
MADE IN THE BRAIN JUST LIKE, THE
CLASSIC NEUROSTEROIDS THAT PAUL
[INDISCERNIBLE] DESCRIBED AS
METABOLITES OF PROGESTERONE IN
THE BRAIN OR AT LATEST ALL THE
SYNTHETIC ENZYMES ARE REQUIRED
AND PRESENT AND HAVE BEEN
IDENTIFIED IN THE BRAIN AND
CERTAIN LYE, I THINK IN MANY OF
THE SYSTEMS, PARTICULARLY IN THE
SOCIAL MODELS WITH THE VOLES,
TOM [INDISCERNIBLE]'S WORK AND
YOUNG'S WORK, THE WIRING OF
ESTRO GENRE SEPTORSORS BOTH ER
ALPHA AND ER BETA AS TO THE
REGULATION OF OXYTOCIN AND BASAL
DEPRESS ANT LOOK AT THE MODEL
FOR HOW THOSE MAY INTERACT AND
THE VARIABILITY THAT MAY OCCUR
IN THEM.
AS YOU SAID, THEY'RE
PROBLEMATIC, THEY'RE EASIER TO
MEASURE THAN THEY USED TO BE 20
YEARS AGO BUT THEIR PROBLEM WITH
HOW THEY GET INTO THE BRAIN,
WHERE THEY INTERACT, I THINK IN
SOME OF THE ANIMAL STUDIES, IT'S
CLEAR IF YOU GIVE VASO-PRESSIN
IN FEMALES THERE WILL BE KIND OF
A FRIEND AND BEFRIEND ACTION
WHEREAS, YOU GIVE IT TO MALES
THEY GET MORE DEFENSIVE AND MORE
TERRITORIAL.
SO THERE'S WONDERFUL SEXER
DIFFERENCES AND BEHAVIOR, AND
SEX DIFFERENCES IN BRAIN, IT'S
JUST IT'S KIND OF LIKE
[INDISCERNIBLE] MYTH THAT
THERE'S SO MANY CHOICES IT
STARTS GETTING VERY COMPLICATED
BUT WOULD BE HAPPY TO TALK WITH
YOU AND CARLOS ABOUT THIS.
>> THANK YOU DR. SCHMIDT FOR
SHARING YOUR WORK AND INSIGHTS
ON THIS VERY IMPORTANT PROBLEM.
WE DO HAVE A COUPLE QUESTIONS
THAT CAME IN FROM OUR VIDEOCAST
VIEWERS, 1 IS HOW DOES ANOREXIA
IN A TIME OF PERIMENOPAUSE
AFFECT THE HORMONE LEVELS IN
DEPRESSION?
>> GOOD QUESTION.
WHEN I WAS IN TRIAL, I WORKED A
FAIR AMOUNT BECAUSE THERE WAS A
BIG PROGRAM ON EATING DISORDERS,
SO I THINK THE MAIN WORK ON THAT
EITHER IN SAN DIEGO OR IN
HARVARD, I DON'T THINK ANYBODY'S
EVER LOOKED AT THE, WHEREVER YOU
ARE, SORRY, I KEEP LOOKING AT
YOU.
>> IT'S OKAY.
>> I DON'T KNOW IF ANYBODY'S
LOOKED AT WHETHER OR FOLLOWED
WOMEN WITH OR MEN WITH EATING
DISORDERS THAT IS A GO THROUGH
THE MENOPAUSE TRANSITION.
I THINK THE--YOU KNOW IT'S
SYRUPLY THE ENDOCRINE EFFECTS OF
STARVATION ARE VERY PROMINENT
AND CAN INDUCE AMENERRIA LIKE
SARAH BURGER'S WORK AND OTHER
VERY LONGS HAVE SHOWN THAT WHEN
THERE'S A CERTAIN THRESHOLD OF
CALORIES INTAKE BELOW WHICH THE
REPRODUCTIVE ACTS SHUTS DOWN,
IT'S CONSIDERABLY VARIABLE
ACROSS WOMEN BUT INN REXIO THAT
IS 1 OF THE GREAT COMPLICATIONS
AND WOMEN OR GIRLS WITH
ANOREXIA, THAT OFTEN PREVENT
THEM FROM GETTING INTO THE
PUBERTY EXPE 1 OF THE PROBLEMS
WE USED TO FACE INTRADA IS WHEN
THOSE GIRLS START GETTING REFED
AND THEIR AXIS STARTS
REACTIVATING THEN THEY START
MAKING ESTROIEN AND THEIR BONES
SURDENLY START CLOSING AND THEY
MAY BE AT REFRESHING FOR SHORT
STARTY STATURE SO WE WOULD HAVE
TO PROLONG SUPPRESSION OF
PUBERTY IN THEM WHILE THEY WERE
REFEEDING AND LET THINGS HAPPEN
MORE TBRADDUALLY.
THERE'S ALSO BEEN CANNED WHAT'S
GROUP UP IN HARVARD DEMON
TRAITED RELEVANCE OF SOME
ANDROGENS PARTICULARLY
TESTOSTERONE IN THAT GROUP.
TO BE HONEST I THINK A LOT OF
WOMEN WITH EATING DISORDERS GET
LOST AS THEY AGE AND I THINK
THAT WHAT HAPPENS, THERE USED TO
BE A SENSE THAT THESE THINGS
WOULD JUST BECOME CHRONIC AND
THE WOMAN IF THEY SURVIVED TO
THAT AIM, THEY WOULD HAVE FOUND
BALANCE BETWEEN THEIR EATING
DISORDER AND KIND OF STAYING
ALIVE.
SOIME NOT SURE WHAT HAPPENS, TO
BE HONEST.
>> GREAT.
THANK YOU NIT'S PROBABLY NOT
GOING TO HELP IF THEY STOP
EATING AS THEY GO THROUGH THE
MENOPAUSE NAS A PEDIATRIC
CARDIOLOGIST, I WOULD PROBABLY
APREWITH THAT.
ANOTHER QUESTION THAT CAME IN IS
HOW DOES SURGICAL MENOPAUSE I.
E. HYSTERECTOMY ALTER THE
INFLMATORY RESPONSE OF DECLINE
IN HORMONES FROM THE RAPID
INDUCTION COMPARED TO
QUOTE-UNQUOTE NORMAL BIOLOGICAL
PROGRESSION OVER TIME?
>> YES, SO, IT MIMICS WHAT A
WOMAN GOES THROUGH, THE NATURAL
MENOPAUSE IN MANY WAYS AS THE
QUESTIONER ASKS OR SUGGIESTED
IT'S MUCH MORE RAPID, WITH THE
OVARIES REMOVED YOU ALSO LOSE A
PORTION OF TESTOSTERONE
PRODUCTION THAT IS PRESENT BY
THE OVAFYS, IT'S A LOT OF
DENOAFY TESTOSTERONE OR
CONVERSION OF HORMONES LIKE
ADRENAL ANDROGENS INTO
TESTOSTERONE.
SO THAT IS AN ARK DITIONAL
ELEMENT.
THE EPIDEMIOLOGY, AND AND THERE
HAS BEEN BOTH STUDIES SUGGESTING
THERE CAN BE SIMILAR NATIVE
EFFECTS ON MOOD AND COGNITION
BUT THERE ALSO HAS BEEN SOME
CENTER FOR EXCELLENCE ON AGINGS
WHETHER IT'S A SURGICAL
[INDISCERNIBLE].
AND MORE RECENT PAPERS IN
SCIENCE OR THE LAST COUPLE OF
YEARS SUGGESTING OVARIAN
SUPPRESS OR GONE ADAL
SUPPRESSION MAY HAVE BENEFICIAL
EFFECTS ON COGNITIVE FUNCTION
DOWN THE ROAD SO THE GAIP IS
SOMETHING THAT THERE'S A MIXED
COHORT IN TERMS OF FOR A THEY
MAY CONTRIBUTE TO MOOD OR
COGNITIVE CHANGES SO IT'S LESS
CLEAR I THINK THAN KIND OF SOME
OF THESE STUDIES.
>> NEXT JUST A COMMENT, THANK
YOU DR. SCHMIDT FOR SUCH A
THOUGHT-PROVOKING HELPFUL
INFORMATION, I LOOK FORWARD
ABOUT READING MORE FOR THIS
CLINICAL RESEARCH AREA.
>> THANK YOU VERY MUCH.
>> YEAH.
>> JUST 1 COMMENT SO ROANA LAB
HERE AT THE NIH HAS A VERY
INTERESTING STORY THAT SOMEBODY
SHE WILL SHARE RELATED TO ER
BETA AND AGE RELATED HEARING
LOSS IN WOMEN, SO THAT'S
SOMETHING THAT THEY'RE VERY
INVESTED IN AND WE'RE WORKING
WITH THEM TO TRY TO SEE IF WE
CAN FIND SOME OF OUR COMPOUND TO
LOOK AT IN THAT GROUP.
>> I WAS GOING TO ASK A QUESTION
ABOUT KEEPING THESE WOMEN IN THE
TRIAL DESPITE APPARENT
DEPRESSION AND HOW MUCH WORK IT
IS TO FOLLOW PATIENTS
LONGITUDINALLY IN THESE TYPES OF
TRIALS?
>> YES, YES, WELL IT'S YOU CAN
ASK XIOMING ABOUT IT, IT'S WORSE
FROM THE PEDIATRIC END
APPARENTLY, I TRY TO STAY AWAY
FROM THAT GROUP, I LIKE TO HEAR
REPORTS WHEN STAFF ARE
MISBEHAVING THAT'S MY MAIN ROLE
BUT OTHERWISE IT'S HANDS-OFF.
BUT IN PERIMENOPAUSE, THE WOMEN
WHO DEVELOPED DEPRESSION, IT'S
OCCURRING IN A CONTEXT OF A
RELATIONSHIP, SO IN CONTRAST TO
WHAT MANY PEOPLE THINK ABOUT THE
RESEARCH, WE'RE--YOU KNOW
FOLLOWING THEM VERY CLOSE AND WE
TAKE THE TIME TO DEVELOP THESE
RELATIONSHIPS AND THEIR VERY
CONNECTED TO THE STAFF, ALL 5 OR
6 THAT ARE HERE SO THEY'LL TALK
TO US AND I THINK WE'LL WORK
WITH THEM AS TO WHETHER THIS IS
SOMETHING THAT THEY FEEL THEY
WOULD LIKE TO COPE WITH, MANY OF
THESE DEPRESSIONS WERE
IDENTIFIED EARLY ON AND WERE
MORE MINOR WHICH WE KNOW CAN
DEVELOP INTO MORE MAJOR
DEPRESSIONS, YOU KNOW THE POINT
WOULD BE THERE WOULD BE A LINE
WHERE THEY WOULD NOT FEEL
COMFORTABLE AND THEY WOULD BE
WANTING TREATMENT AND THEY WOULD
STOP THE STUDY.
AND WE WOULD JUST FOLLOW THEM
MAYBE TO FIND OUT WHEN THEIR
LAST MENSTRUAL PERIOD WAS AND
THERE'S A NUMBER OF THOSE WOMEN
THAT WERE THERE.
OTHERS, YOU KNOW, WE WERE
WILLING TO GO WITH WHAT THEY
WANTED TO DO AND THEY FELT THAT
THEY WERE COPING FINE. THIS AN
OUTPATIENT DEPRESSION AND THEY
WANTED TO SEE WHETHER IT WOULD
REMIT ON ITS OWN AND THEY WOULD
CARRY ON AND SOME OF THEM DID,
OTHERS DIDN'T.
AND THERE'S A LOT OF MEDICAL
ILLNESS THAT HAPPENS AT THIS
TIME AND THOSE WOMEN WERE
EXCLUDED FROM THE DATA ANALYSIS,
BUT YOU KNOW A LOT OF MEDICAL
THINGS HAPPEN YOU KNOW KIND OF
TRIBUTE TO DEPRESSION BUT THAT
WE COULDN'T SOLELY ACKNOWLEDGE
ITS LINK TO THE PERIMENOPAUSE.
BUT IN THE CLINIC WHEN WE SEE
THEM THIS OFTEN, THAT'S WHERE
EACH OF THEM IS LIKE A CASE
REPORT, PROGRESS NOTES AND WE
CAN LOOK BACK ON THAT AND SEE
WHAT WAS HAPPENING WITH EACH
INDIVIDUAL WOMAN.
AND THAT'S THE IMPORTANCE OF THE
ABILITY OF THESE LONGITUDINAL
STUDIES AT NIH BECAUSE IN AN
EPIDEMIOLOGIC STUDY, YOU KNOW,
THERE'S THE HUGE DATA COLLECTION
EFFORT THAT STANDS BETWEEN YOU
AND THE PATIENT AND SO THERE'S
CERTAIN NUANCE EVENTS OF THEIR
EXPERIENCE THAT DON'T GET
CAPTURED AND THE RELATIONSHIP IS
NOT THERE SO YOU MAY NOT
ACTUALLY HAVE CHANNELS OPEN TO
HEAR ABOUT SOME OF THESE THINGS.
SO ...
>> SO DR. SCHMIDT, MIGHT A WOMAN
WHO HAS A HISTORY OF DEPRESSION
REQUEST HER GYNECOLOGIST OR PC P
REQUEST THEY MEASURE HER FSH IN
HER PERIMENOPAUSAL PERIOD IN.
>> YEAH, I THINK THE CRITERIA,
THE STAGES OF REPROUCT DIDDIVE
ANALLING WORKSHOP, THEY RELY
LESS ON FSH AND INHIB THORSIN
ISSUE THE ASSAY IS GETTING
BETTER, I'M NOT SURE IT'S READY
FOR PRIME TIME BUT I THINK THE
MOST IMPORTANT CRITERIA WOULD BE
IF THEY ARE SKIPPING CYCLES OR
IF THEIR CYCLES HAVE CHANGED IN
LENGTH.
THEY TALK ABOUT A WEEK SHORTER
OR A WEEK LONGER, IF THERE'S A
CHANGE IN THE BLOODING PATTERN,
OFTEN PLEADING BECOME HEAVIER
DURING THIS TIME, PLUS OR MINUS
OTHERRICISM TOPS OF
INSUFFICIENCY, WHETHER IT'S
VAGINAL DRYNESS OR HOT FLASHES,
THEY NOT NEED TO CONFIRM THAT
BUT CERTAINLY HAD MANY WOMEN IN
THE CLIPPIC THEY HAVE HAD
MEASURES OF FSH, ESTRO DIAL, THE
ASSAYS FOR ESTRA-DIAL WHEN IT
GERONTOLOGYSTSS LOW ARE NOT VERY
RELIABLE UNLESS YOUR USING
THINGS LIKE MASS SPEC, SO MANY
GYNECOLOGISTS WILL DO THAT BUT
MANY OF THEM ALSO WILL FEEL
COMFORTABLE JUST BY THE WOMAN'S
AGE AND SOME OF THE OTHER
SYMPTOMS OF THEIR MENSTRUAL
CYCLE HISTORY THIS THEY DON'T
REQUIRE.
HORMONE MEASURES.
>> WE MAYBE HAVE TIME FOR 1 LAST
QUESTION.
THIS WILL BE SHORT.
HAD MANY OF THE PATIENTS IN YOUR
STUDY SUFFERED FROM PTSD?
>> WELL IT'S SOMETHING THAT
CONSTANCE IS LOOKING AT.
I THINK WE ARE LOOKING AT EARLY
LIFE TRAUMA.
SO I THINK THAT IS WHAT WE FELT
WAS IMPORTANT.
NONE OF THE MET CRITERIA ON THE
STRUCTURED DIAGNOSTIC INTERVIEW
FOR PTSD KIND OF BEFORE HAND, AT
LEAST NOT MANY OF THEM, BUT MANY
OF THEM DO HAVE AND THERE IS A
LITERATURE RELATED TO EARLY LIFE
STRESS WHICH IS A COMPLICATED
RELATIONSHIP WITH REPORTS OF
PTSD, BOTH IN TERMS OF
FALSE-NEGATIVES AND
FALSE-POSITIVES BUT WE HAVE THAT
INFORMATION AND WE WILL BE
LOOKING AT THAT.
BUT CERTAINLY IN WOMEN IN
GENERAL WHO PRESENT TO
BEHAVIORIAL HEALTH CLINICS,
THERE'S ABOUT A 60% OR HIGHER
RATE OF EARLY LIFE TRAUMA, SO, I
THINK THAT'S WHY PTSD IS NOT AN
UNCOMMON ANTISEEDENT TO A LOT OF
THESE CONDITIONS.
THANK YOU.
I THINK THAT REALLY IS IT.
THANK YOU.