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WELCOME TO THE CLINICAL
CENTER GRAND ROUNDS,

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A WEEKLY SERIES OF EDUCATIONAL
LECTURES FOR PHYSICIANS AND

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HEALTH CARE PROFESSIONALS
BROADCAST FROM THE CLINICAL

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CENTER AT THE NATIONAL
INSTITUTES OF HEALTH IN

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BETHESDA, MD.

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THE NIH CLINICAL CENTER IS THE
WORLD'S LARGEST HOSPITAL TOTALLY

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DEDICATED TO INVESTIGATIONAL
RESEARCH AND LEADS THE GLOBAL

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EFFORT IN TRAINING TODAY'S
INVESTIGATORS AND DISCOVERING

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TOMORROW'S CURES.

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LEARN MORE BY VISITING US ONLINE
AT HTTP://CLINICALCENTER.NIH.GOV

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THANK YOU ALL FOR JOINING US

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TODAY ONLINE AND IN PERSON.

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VERY NICE TO SEE EVERYONE HERE.

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IT'S MY GREAT PLEASURE TO

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WELCOME YOU TO TODAY'S CLIPICAL

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CENTER GRAND ROUNDS.

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THE HOPKINS CLOUD CME ARCKIVITY

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CODE FOR TODAY'S GRAND ROUNDS

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AND 50529.

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AND TEXT THIS CODE TO JOHNS

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HOPKINS CME PHONE NUMBER ON THE

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SLIDE AND THEN YOU CAN RECEIVE

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YOUR CME CREDIT IF ARE THIS

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LECTURE.

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WE KINDLY INVITE TO YOU PRORIDE

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ANY FEEDBACK ON TODAY'S LECTURE

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BY SCANNING THE QR CODE ON THE

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CME SLIDE AND FOR THOSE APPLYING

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FOR CME, YOU WILL RECEIVE A

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FEEDBACK SURVEY VIA E-MAIL LINK.

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THE SURVEY WILL BE USED TO

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PROVIDE US WITH IMPORTANT

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FEEDBACK ABOUT THIS PRESENTATION

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AND ALLOWS TO YOU SUBMIT ANY

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SUGGESTIONS FOR FUTURE GRANDS

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ROUNDS TOPICS, FOLLOWING THE

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PRESENTATION QUESTIONS FOR THE

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SPEAKER WILL BE TAKEN FROM

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MICROPHONES IN THE AISLES, AS

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WELL AS VIDEOCAST VIEWERS MAY

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SUBMIT A QUESTIONS AT ANY TIME

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BY SCROLLING DOWN AND CLICKING

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THE LIVE FEEDBACK BUTTON LOCATED

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ON THE VIEDMANIOY CAST WEBSITE.

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QUESTIONS WILL BE ANSWERED AS

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TIME PERMITSA THE CONCLUSION OF

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THE PRESENTATION.

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SO I'M VERY PLEASED AS THE

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CLINICAL DIRECTOR OF NIMH TO

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INTRODUCE TODAY'S SPEAKER,

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DR. PETER SCHMIDT.

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HE'S THE CHIEF OF THE

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BEHAVIORIAL ENDOCRINE BRANCH OF

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THE NATIONAL INNSITUTE OF MENTAL

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HEALTH AND HE'S THE DIRECTOR OF

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THE CLINIC ON OP4.

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HE EARNED HADIS BACHELORS FROM

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THE UNIVERSITY OF TORONTO, HE

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THEN EARNED A BACHELOR'S OF

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MEDICINE AND SURGERY WITH HONORS

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WITH THE ROYAL COLLEGE OF

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SURGEONS IN IRELAND, AND HE

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RETURNED TO THE UNIVERSITY OF

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TORONTO WHERE HE COMPLETED HIS

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RESIDENCY IN PSYCHEISTRY AND

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CAME TO THE NIMH IN 1986, FIRST

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TO THE UNIT IN PEPTIDE STUDIES

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IN THE BIOLOGICAL PSYCHIATRY

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BRANCH AND JOINED WHAT IS NOW

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KNOWN AS THE BEHAVIORIAL

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ENDOCRINE BRANCH THAT HE NOW

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LEADS.

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MANY MAY NOT KNOW THAT

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DR. SCHMIDT ALSO SERVED AS

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DREBTOR AND SOCIAL DIRECTOR OF

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THE PSYCHIATRY LIAISON SERVICE

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BEFORE I ARRIVED AND HE'S BEEN A

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TRUSTED CLINICAL ADVISOR ON THE

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OP4 ACTIVITIES AND THE IRP.

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DR. SCHMIDT SERVES AS AN

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ASSOCIATE PROFESSOR IN THE MOOD

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PROGRAM AT THE UNIVERSITY OF THE

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MARYLAND A POSITION SINCE 2000

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AND ADJUNCT PROFESSOR OF THE

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DEPARTMENT OF PSYCHIATRY AT THE

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UNIVERSITY OF NORTH CAROLINA

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CHAPEL HILL.

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A POSITION HE'S HELD SINCE 2007.

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HE HAS OF COURSE SERVED ON

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NUMEROUS NIH COMMITTEES WRITTEN

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200 PAPERS INCLUDING IN THE NEW

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ENGLAND JOURNAL MANY IN THEIR

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JAMA, JOURNAL OF PSYCHIATRY AND

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MOLECULAR PSYCHIATRY, IF I SPEND

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ALL MY TIME TELLING BUT HIS

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PAPER AND AWARDS HE WOULDN'T GET

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TO HIS LECTURE EMPLOY HE'S

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SERVED ON THE PREMEN TRAL

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DYSPHORIC GROUP, CHAIRED ON THE

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SOCIETY OF NEUROPHARMA COALING

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AND AT NIMH THE WORK THAT

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DR. SCHMIDT AND HIS COLLEAGUES

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HAVE WORKED ON HAS LED TO THE

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IMPORTANT ENDOCRINE MODELS THAT

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CLARIFY THE ROLE OF REPRODUCTIVE

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HORMONES OF MOOD DEVELOPMENT

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DISORDERS IN WOMEN.

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HIS LABORATORY STUDIES, THE

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RELATIONSHIP BETWEEN HORMONE

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STRESS AND MOOD PARTICULARLY IN

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THE AREAS OF POSTPARTUM,

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DEPRESSION, SEVERE PREMENSTRUAL

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DYSPHORIA AND PERIPAUSAL

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DEPRESSION, HIS LAB BEGAN

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INITIATIVE TO LONGITUDINALLY TO

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THE DEVELOPMENT EFFECTS OF SEX

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STEROIDS DURING PUBERTY, I

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APPRECIATE HIS RIGOR AND

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MENTORING, TODAY HE WILL PRESENT

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HIS LECTURE ENTITLED DEPRESSION

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DURING PERIMENOPAUSE, ENDOCRINE

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CHARACTERISTICS.

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PLEASE JOIN ME IN WELCOMING

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DR. SCHMIDT.

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[ APPLAUSE ]

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>> THANK YOU MARILYN FOR
THOSE

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GENEROUS COMMENTS AND I'M DPLAD

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OUR CONVERSATIONS HAVE BEEN

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MUTUALLY USEFUL.

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JUST TO GET STARTED I HAVE

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NOTHING TO DISCLOSE.

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I WILL BE MENTIONING IN PASSING,

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THE USE OF EXPERIMENTAL USE OF

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AN ESTROGEN RECEPTOR BETA

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AGONIST IN THE TREATMENT OF

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POTENTIAL TREATMENT OF

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PERIMENOPAUSAL DEPRESSION.

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LEARNING OBJECTIVES WILL BE

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FOCUSING ON THE RELATIONSHIP, OR

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STUDIES ON THE RELATIONSHIP

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BETWEEN DEPRESSION AND THE

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PERIMENOPAUSE.

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SO MUCH OF OUR WORK IN THE

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CLINIC AS FOCUSED ON

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REPRODUCTIVE MOOD DISORDERS BUT

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AS MARILYN MENTIONED, WE'VE ALSO

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STARTED AN INITIATIVE IN

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COLLABORATION WITH KAREN BERM AN

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AND JACK AND LINNET, AND TRYING

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TO UNDERSTAND THE IMPACT OF THE

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PHYSIOLOGIC EVENTS RELATED TO

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PUBERTY ON NORMAL BRAIN

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DEVELOPMENT OR TYPICAL BRAIN

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DEVELOPMENT.

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MOST OF MY WORK OVER THE LAST

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DECK'SS HAVE FOCUSED ON 2

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QUESTIONS, FIRST, IS ARE THESE

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REPRODUCTIVE MOOD DISORDERS

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LINKED TO THE PERIODS OF

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REPRODUCTIVE ENDOCRINOLOGY IN

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WHICH THEY ARE REPORTED TO

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OCCUR.

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AND SECOND, IF THAT'S THE CASE,

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THEN WHAT WOULD BE THE MECHANISM

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WHEREBY A CHANGE, OTHERWISE AH

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TENSIBLY NORMAL CHANGE THIS

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PHYSIOLOGY WOULD TRANSLATE INTO

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AN ALTERATION IN MOOD STATE IN

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THESE WOMEN.

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SO THESE ARE THE CONDITIONS THAT

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WE STUDY. 

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PERPERIMEN PAUSAL DEPRESSION,

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PERIMENSTRUAL DISORDER,

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POSTPARTUM DEPRESSION, KAREN AND

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I ARE STARTING A NEW INITIATIVE

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ON POSTPARTUM PSYCHOSIS.

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SO THESE CONDITIONS ARE

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PREVALENT, THEY'RE ASSOCIATE

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WIDE CONSIDERABLE DISABILITY,

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THEY OCCUR IN WOMEN AT DIFFERENT

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PHASES OF THEIR LIFE CYCLE.

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BUT THEY'RE NOT FROM WHAT WE

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UNDERSTAND THE SAME CONDITION

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AND IN CONTRAST TO TYPICAL

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ENDOCRINE OPEN MEETINGATHY SAY

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HYPO OR HYPER THYROIDISM WHERE

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BRAIN SYMPTOMS CAN OCCUR IN SOME

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PEOPLE WHO HAVE TOO HIGH OR TOO

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LOW THYROID HORMONE.

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THERE'S NO EVIDENCE OF

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DEFICIENCY OF EXCESSIVE HORMONE

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IN ANY OF THESE CONDITIONS AND

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THERE'S BEEN MULTIPLE STUDIES TO

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KIND OF CONFIRM THAT, SO THESE

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ARE NOT TYPICAL ENDOCRINE

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OPERATING GLOBALLYATHYS PER SE,

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WHAT WE HAVE NOTICED IS ACROSS

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ALL THESE CONDITIONS IS A TERM

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CALLED THE DIFFERENTIAL

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SENSITIVITY WHICH IS NOT

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UNFAMILIAR IN ENDOCRINOLOGY OR

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ANY OTHER BRARCH BRAP OF

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MEDICINE WHERE THE SAME CHANGE

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IN A HORMONE ELICIT A CHANGE IN

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WOMEN THAT ARE AT RISK THAT'S

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UNSEEN AND IN UNAFFECTED WOMEN.

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HOWEVER THE HORMONE AT CHANGE

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DIFFERS ACROSS THE CONDITIONS

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WHERE MAYBE THE EXPOSURE TO

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HORMONES THAT TRIGGER TRIGGER

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SYMPTOMS AND PREMENSE STRAL

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DYSPHORIC DISORDER WHERE IT

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SEEMS TO BE THE WITHDRAWAL OF

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HORMONES IN SYMPTOMS AND

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POSTPARTUM DEPRESSION OR AS I

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WILL SHOW YOU LATER IN MY TALK,

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PERIMENOPAUSAL DEPRESSION.

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SO WHAT I WILL DO TODAY IS

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FOCUSING ON REALLY, OUR TODAYS

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ON THE RELATIONSHIP BETWEEN

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DEPRESSION AND THE MENOPAUSE

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TRANSITION OR THE PERIMENOPAUSE.

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I'LL TALK ABOUT OUR WORK IN THE

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LONGITUDINAL STUDY FOLLOWING

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PERSPECTIVELY, WOMEN AS THEY GO

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THROUGH THE MENOPAUSE

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TRANSITION, STUDIES ELECTRICKING

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AT THE EFFECTS OF

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ESTRADISCIPLINARYOLE WITHDRAWAL

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IN MOOD SYMPTOMS IN THESE

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MENTION AND A BREF MENTION OF AN

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ONGOING TRIAL WHERE WE'RE

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LOOKING AT THE EFFECTS OF AN E.

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R. BETA AGONIST IN THIS

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CONDITION AND THEN I WILL END

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THIS WORK THAT WE DO IN

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COLLABORATION WITH DAVID

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GOLDMAN'S LABORATORY WHERE WE

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TRY TO DEVELOP INVITRO MODELS TO

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RECAPITULATE THE HORMONAL

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EXPERIMENTS WE DO IN THE CLINIC

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AND TRY TO UNDERSTAND SOME OF

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THE CELLULAR, UNDERLYING

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CELLULAR BIOLOGY AND SIGNALING

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THAT MAY BE PRESENT IN THESE

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WOMEN.

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SO JUST TO START WITH, BACK IN

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2000, PRIOR TO THAT THERE IS NOT

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MUCH OF AN AGREEMENT OR

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CONSENSUS ON WHETHER THERE'S ANY

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ASSOCIATION BETWEEN DEPRESSION

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AND MENOPAUSE.

253
00:09:18,857 --> 00:09:21,659
AND THAT WAS LARGELY RELATED TO

254
00:09:21,659 --> 00:09:25,430
WORK DONE IN A CONDITION CALLED

255
00:09:25,430 --> 00:09:27,766
INVOLUNTEERSUTIONAL MEL AN

256
00:09:27,766 --> 00:09:29,167
ALCOHOLLIA, BUT SEVERAL STUDIES

257
00:09:29,167 --> 00:09:31,603
THAT WERE COMMUNITY BASED, LARGE

258
00:09:31,603 --> 00:09:32,303
SCALE, PROSPECTIVELY FOLLOWING

259
00:09:32,303 --> 00:09:35,473
WOMEN AS THEY WENT THROUGH THEIR

260
00:09:35,473 --> 00:09:37,308
REPRODUCTIVE STATES THROUGH

261
00:09:37,308 --> 00:09:39,344
THEIR LAST MENSTRUAL PERIOD,

262
00:09:39,344 --> 00:09:40,211
IDENTIFIED THAT FOR SOME WOMEN,

263
00:09:40,211 --> 00:09:42,347
THIS WAS A PERIOD OF INCREASED

264
00:09:42,347 --> 00:09:42,947
RISK FOR DEPRESSION.

265
00:09:42,947 --> 00:09:45,784
IN FACT, THERE WAS A 2-3 FOLD

266
00:09:45,784 --> 00:09:47,952
INCREASED RISK OF BOTH FIRST

267
00:09:47,952 --> 00:09:49,287
ONSET, SO IT'S NOT JUST WOMEN

268
00:09:49,287 --> 00:09:51,456
WHO HAD A PREVIOUS DEPRESSION,

269
00:09:51,456 --> 00:09:54,492
BUT ALSO RECURRENT DEPRESSIONS.

270
00:09:54,492 --> 00:09:57,162
SO THAT SUDDENLY

271
00:09:57,162 --> 00:09:58,063
SHOWED--DEMONSTRATED A SIGNAL

272
00:09:58,063 --> 00:10:00,031
THAT WAS PRESENT BUT IT WAS NOT

273
00:10:00,031 --> 00:10:01,933
IN THE POST MENOPAUSE, IT WAS IN

274
00:10:01,933 --> 00:10:03,334
THE TRANSITION FROM REPRODUCTIVE

275
00:10:03,334 --> 00:10:06,237
LIFE TO THE MENOPAUSE.

276
00:10:06,237 --> 00:10:09,074
THE ESTIMATES ARE THAT THIS MAY

277
00:10:09,074 --> 00:10:11,476
OCCUR IN 20-30%.

278
00:10:11,476 --> 00:10:14,012
SO WHAT'S CLEAR IS THAT THE MAR

279
00:10:14,012 --> 00:10:17,182
JORRITY OF WOMEN GO THROUGH THE

280
00:10:17,182 --> 00:10:18,116
MENOPAUSE TANSITION WITHOUT

281
00:10:18,116 --> 00:10:19,717
DEVELOPING ANY KIND BE OF

282
00:10:19,717 --> 00:10:21,719
AFFECTIVE OR MOOD DISTURBANCE.

283
00:10:21,719 --> 00:10:23,354
FOR SOME IT CAN BE VERY

284
00:10:23,354 --> 00:10:23,621
IMPORTANT.

285
00:10:23,621 --> 00:10:25,123
ADDITIONALLY FROM THE WOMEN'S

286
00:10:25,123 --> 00:10:26,324
HELT INITTIAIVE IT AND OTHER

287
00:10:26,324 --> 00:10:28,026
STUDIES SHOWED THAT EVEN THE

288
00:10:28,026 --> 00:10:30,195
PRESENCE OF MINOR DEPRESSION IN

289
00:10:30,195 --> 00:10:31,863
A PERIOR POST MENOPAUSAL WOMEN

290
00:10:31,863 --> 00:10:34,466
THAT OVER A 5 YEAR FOLLOW UP

291
00:10:34,466 --> 00:10:36,134
PERIOD CONTROLLING FOR OTHER

292
00:10:36,134 --> 00:10:39,003
RISK FACTORED SHOWED A 50%

293
00:10:39,003 --> 00:10:39,838
INCRACY IN CARDIOVASCULAR

294
00:10:39,838 --> 00:10:40,972
MORTALITY SO THIS IS SOMETHING

295
00:10:40,972 --> 00:10:43,842
THAT IS IN THE SICKIATRIC

296
00:10:43,842 --> 00:10:45,510
LITERATURE WHERE THERE'S A

297
00:10:45,510 --> 00:10:47,112
CLUSTERING OF DEPRESSION,

298
00:10:47,112 --> 00:10:49,380
METABOLEC DYSFUNCTION AND HEART

299
00:10:49,380 --> 00:10:51,082
DISEASE AND GIVEN THAT THIS IS

300
00:10:51,082 --> 00:10:53,051
THE HEART DISEASE IS THE NUMBER

301
00:10:53,051 --> 00:10:55,820
1 CAUSE OF MORTALITY IN WOMEN AT

302
00:10:55,820 --> 00:10:58,623
THIS AGE, THAL SEEMED TO BE A

303
00:10:58,623 --> 00:11:00,658
PRETTY IMPORTANT POTENTIAL

304
00:11:00,658 --> 00:11:03,528
MEDICAL SEQUELA OF DEPRESSION

305
00:11:03,528 --> 00:11:04,929
DURING THE PERIMENOPAUSE AS WELL

306
00:11:04,929 --> 00:11:06,764
AS EMOTIONAL DISABILITY THAT

307
00:11:06,764 --> 00:11:07,398
ACCOMPANYS IT.

308
00:11:07,398 --> 00:11:10,668
SO WHAT HAPPENS DURING THE

309
00:11:10,668 --> 00:11:10,969
MENOPAUSE?

310
00:11:10,969 --> 00:11:12,570
AS YOU KNOW WOMEN WITH OVARIES

311
00:11:12,570 --> 00:11:18,243
ARE BORN WITH ABOUT 400, 500,000

312
00:11:18,243 --> 00:11:20,678
PRIMORDIAL FOLLICLES IN THEIR

313
00:11:20,678 --> 00:11:21,880
OVARIES AND THERE'S AN ATTRITION

314
00:11:21,880 --> 00:11:27,685
OF THESE OVER THE COURSE OF YOU

315
00:11:27,685 --> 00:11:30,088
KNOW EACH OFUE LATTERY CYCLE AND

316
00:11:30,088 --> 00:11:30,588
WITH AGE.

317
00:11:30,588 --> 00:11:34,125
HOWEVER, THERE IS A RAPID

318
00:11:34,125 --> 00:11:35,627
DECLINE AT AROUND AGE 40,

319
00:11:35,627 --> 00:11:37,996
MIDLIFE IN WOMEN THAT IS RELATED

320
00:11:37,996 --> 00:11:41,933
AND ULTIMATELY ENDS IN THE

321
00:11:41,933 --> 00:11:42,200
MENOPAUSE.

322
00:11:42,200 --> 00:11:45,603
NOW THIS IS A SLAYED I BORROWED

323
00:11:45,603 --> 00:11:48,573
IN JAN HALL WHO'S DOWN IN NORTH

324
00:11:48,573 --> 00:11:49,874
CAROLINA MANY YEARS AGO SO THIS

325
00:11:49,874 --> 00:11:52,644
IS A KEEMATTIC OF THE 3, OF THE

326
00:11:52,644 --> 00:11:58,950
LEVELS OF CONTROL OF

327
00:11:58,950 --> 00:12:04,956
REPRODUCTIVE AXIS AND GNRH IS

328
00:12:04,956 --> 00:12:07,725
STIMUTING THE PITUITARYY FOR LH

329
00:12:07,725 --> 00:12:09,827
AND FSH, WHICH STIMULATE THE

330
00:12:09,827 --> 00:12:10,195
OVARY.

331
00:12:10,195 --> 00:12:12,096
THE OVARY PRODUCES A NUMBER OF

332
00:12:12,096 --> 00:12:13,164
HORMONES INCLUING 2 TERROIDS

333
00:12:13,164 --> 00:12:17,035
THAT WILL BE FOCUSING ON,

334
00:12:17,035 --> 00:12:17,535
ESTRADISCIPLINARYOLE AND

335
00:12:17,535 --> 00:12:18,670
PROJECTOR OWN AS WELL AS SOME

336
00:12:18,670 --> 00:12:22,106
KIND OF SMALL PROTEIN MOLECULES,

337
00:12:22,106 --> 00:12:25,743
THE INHIB THORSINS AND THE

338
00:12:25,743 --> 00:12:28,046
FOLLICLE STATINS, AND THE INHIB

339
00:12:28,046 --> 00:12:28,513
THORSINS, FEEDBACK AND

340
00:12:28,513 --> 00:12:30,448
ININCREASE IN BODY HIT AT THE

341
00:12:30,448 --> 00:12:32,550
LEVEL OF THE PITUE TARY.

342
00:12:32,550 --> 00:12:36,621
AND AS WHAT HAPPENED IN THE

343
00:12:36,621 --> 00:12:38,923
MENOPAUSE AS ESTROGEN AND

344
00:12:38,923 --> 00:12:40,325
PROGESTERONE LEVELS FALL, INHIB

345
00:12:40,325 --> 00:12:43,895
THORSIN LEVELS DECREASE AND THAT

346
00:12:43,895 --> 00:12:47,599
REMOVES LH AND FSH WHICH ARE

347
00:12:47,599 --> 00:12:48,199
EVENTUALLY TONICALLY ELEVATED.

348
00:12:48,199 --> 00:12:50,034
SO THOSE ARE SOME OF THE MARKERS

349
00:12:50,034 --> 00:12:52,937
OF THE PERO MENOPAUSE WE HAVE

350
00:12:52,937 --> 00:12:53,271
INCLUED.

351
00:12:53,271 --> 00:12:56,507
THIS IS AN OLD SCHEMATIC JUST

352
00:12:56,507 --> 00:12:59,377
SHOWING THE DIFFERENCES IN THE

353
00:12:59,377 --> 00:13:00,245
ESTRA-DIAL AND PROGESTERONE

354
00:13:00,245 --> 00:13:01,546
DIALSA THE LEVEL, AND THE

355
00:13:01,546 --> 00:13:03,748
TROAPINS AT THE LOWER PANEL, AT

356
00:13:03,748 --> 00:13:07,118
3 PHASES OF REPRODUCTIVE LIFE,

357
00:13:07,118 --> 00:13:08,786
DURING THE NORMAL REPRODUCTIVE

358
00:13:08,786 --> 00:13:10,421
LIFE CYCLE, THEN POST MENOPAUSE

359
00:13:10,421 --> 00:13:11,456
AND THEN THE TRANSITION FROM

360
00:13:11,456 --> 00:13:14,692
HERE TO HERE WHICH IS VARIABLY

361
00:13:14,692 --> 00:13:16,661
CALLED THE MENOPAUSE TRANSITION

362
00:13:16,661 --> 00:13:17,695
OR THE PERIMENOPAUSE, DURING THE

363
00:13:17,695 --> 00:13:20,498
COURSE OF THE NORMAL CYCLE,

364
00:13:20,498 --> 00:13:21,766
ESTRADISCIPLINARYOLE HAS THE BI

365
00:13:21,766 --> 00:13:24,902
PHASIC PATTERN OF SECRETION, AND

366
00:13:24,902 --> 00:13:28,039
SECRETION IS LARGELY CONFINED TO

367
00:13:28,039 --> 00:13:30,208
THE LUTEAL PHASE OF THE

368
00:13:30,208 --> 00:13:31,576
MENSTRUAL CYCLE.

369
00:13:31,576 --> 00:13:33,144
FSH INITIALLY INCREASES WHEN THE

370
00:13:33,144 --> 00:13:34,579
INIT FOLLICLE IS RECRUITED

371
00:13:34,579 --> 00:13:35,947
DURING THE EARLY FOLLICULAR

372
00:13:35,947 --> 00:13:40,518
PHASE AND BOTH HAVE PEAKS AROUND

373
00:13:40,518 --> 00:13:42,854
OUR APPROXIMATE TO OFULATION,

374
00:13:42,854 --> 00:13:44,255
DURING POST MENOPAUSE, ESTROIEN

375
00:13:44,255 --> 00:13:48,993
AND MENOPAUSE LEVELS ARE 

376
00:13:48,993 --> 00:13:50,962
CONSISTENTLY LOW, WHEREAS FSH

377
00:13:50,962 --> 00:13:52,597
AND LH ARE TONICALLY ELEVATED

378
00:13:52,597 --> 00:13:54,332
AND YOU STOP SEEING THE

379
00:13:54,332 --> 00:13:55,967
PRODUCTION OF THESE HORMONES.

380
00:13:55,967 --> 00:13:57,902
THE TRANSITION IS QUITE A

381
00:13:57,902 --> 00:14:03,408
VARIABLE PERIOD, THERE ARE FEWER

382
00:14:03,408 --> 00:14:03,808
OFLATTORY CYCLES,

383
00:14:03,808 --> 00:14:04,475
ESTRADISCIPLINARYOLE LEVELS IN

384
00:14:04,475 --> 00:14:06,110
THE MAIORITY OF WOMEN BUT NOT

385
00:14:06,110 --> 00:14:07,645
ALL ARE ACTUALLY LOWER

386
00:14:07,645 --> 00:14:09,314
PROGRESSIVELY LOWER WITH KIND OF

387
00:14:09,314 --> 00:14:13,584
AN INCREASED DECLINE DURING THE

388
00:14:13,584 --> 00:14:18,623
LATE MENOPAUSE TRANSITION, FEWER

389
00:14:18,623 --> 00:14:24,896
OVULATTORY CYCLES FOR LESS

390
00:14:24,896 --> 00:14:25,396
PROGESTERONE.

391
00:14:25,396 --> 00:14:27,899
THE ELEVATED FSH LEVEL WAS 1

392
00:14:27,899 --> 00:14:29,067
MARKER THAT USED TO BE

393
00:14:29,067 --> 00:14:32,704
CONSIDERED AS PART OF SOME OF

394
00:14:32,704 --> 00:14:33,671
THE EARLY DEMONSTRATIONS OF

395
00:14:33,671 --> 00:14:36,441
RELATED TO A WOMAN'S

396
00:14:36,441 --> 00:14:38,576
REPRODUCTIVE AGING USED IN

397
00:14:38,576 --> 00:14:40,745
FERTILITY CLINICS AS WELL, WHERE

398
00:14:40,745 --> 00:14:45,149
SOME OF THE CRITERIA THAT WE'RE

399
00:14:45,149 --> 00:14:46,918
DEVELOPED TO IDENTIFY THE

400
00:14:46,918 --> 00:14:48,086
PERIMENOPAUSE EMPLOY THESE

401
00:14:48,086 --> 00:14:49,620
CRITERIA HAVE BEEN FORMALIZED IN

402
00:14:49,620 --> 00:14:51,122
THE STAGES OF REPRODUCTIVE AGING

403
00:14:51,122 --> 00:14:53,024
WORKSHOP AND SO THE MENOPAUSE

404
00:14:53,024 --> 00:14:55,026
TRANSITION WHICH IS THE TIME

405
00:14:55,026 --> 00:14:57,195
FROM REPRODUCTIVE TO THE POST

406
00:14:57,195 --> 00:14:59,831
MENOPAUSE IS CHARACTERIZED BY

407
00:14:59,831 --> 00:15:01,332
VARIABLE CYCLELING, SKIPPED

408
00:15:01,332 --> 00:15:03,234
PERIODS, OVER ALL AN ELEVATED

409
00:15:03,234 --> 00:15:05,636
FSH LEVELS AND THE PERIMENOPAUSE

410
00:15:05,636 --> 00:15:07,672
HAS BEEN DEFEIGNED AS THAT

411
00:15:07,672 --> 00:15:09,107
PERIOD OF THE TRANSITION PLUS

412
00:15:09,107 --> 00:15:12,276
THE FIRST YEAR AFTER THE LAST

413
00:15:12,276 --> 00:15:13,144
MENSTRUAL PERIOD.

414
00:15:13,144 --> 00:15:15,413
SO THIS REALLY KIND OF

415
00:15:15,413 --> 00:15:17,715
CHARACTERIZES THE ROLLER COASTER

416
00:15:17,715 --> 00:15:19,484
OF ENDOCRINE EVENTS THAT OCCUR

417
00:15:19,484 --> 00:15:20,451
DURING THE MENOPAUSE TRANSITION,

418
00:15:20,451 --> 00:15:22,520
AND THAT'S WHAT WE'RE FOCUSING

419
00:15:22,520 --> 00:15:25,957
ON ON IN OUR STUDIES RELATED TO

420
00:15:25,957 --> 00:15:26,524
DEPRESSION.

421
00:15:26,524 --> 00:15:29,961
SO, JUST AS A BACKGROUND, THE

422
00:15:29,961 --> 00:15:31,996
MENOPAUSE TRANSITION PROBABLY IS

423
00:15:31,996 --> 00:15:33,398
ABOUT--IT CAN LAST FROM ANYWHERE

424
00:15:33,398 --> 00:15:35,933
FROM 1 YEAR OR SHORTER, LIKE THE

425
00:15:35,933 --> 00:15:36,968
LAST NORMAL MENSTRUAL PERIOD

426
00:15:36,968 --> 00:15:40,037
COULD BE THE LAST MENSTRUAL

427
00:15:40,037 --> 00:15:40,438
PERIOD.

428
00:15:40,438 --> 00:15:42,840
IN OTHER WOMEN IT MAY GO ON FOR

429
00:15:42,840 --> 00:15:43,841
UP TO 15 YEARS.

430
00:15:43,841 --> 00:15:45,576
SO IT'S QUITE VARIABLE, IT'S A

431
00:15:45,576 --> 00:15:46,778
LOT OF INDIVIDUAL VARIATION FROM

432
00:15:46,778 --> 00:15:52,116
CYCLE TO CYCLE AND ALSO FROM

433
00:15:52,116 --> 00:15:52,784
WOMAN TO WOMAN.

434
00:15:52,784 --> 00:15:55,153
SO AS WE SUGGESTED THERE'S

435
00:15:55,153 --> 00:15:55,953
EPIDEMIOLOGIC EVIDENT TO

436
00:15:55,953 --> 00:15:57,121
SUGGIEST THAT FOR SOME WOMEN

437
00:15:57,121 --> 00:16:00,591
THIS, IS A PERIOD OF INCREASED

438
00:16:00,591 --> 00:16:01,559
RISK OF DEPRESSION.

439
00:16:01,559 --> 00:16:03,127
WHAT HASN'T BEEN ASKED IS

440
00:16:03,127 --> 00:16:05,196
WHETHER THERE'S DIFFERENCES IN

441
00:16:05,196 --> 00:16:06,230
REPRODUCTIVE FUNCTION THAT

442
00:16:06,230 --> 00:16:10,067
EITHER INCREASE THE RISK FOR OR

443
00:16:10,067 --> 00:16:10,902
ACCOMPANY PERIMENOPAUSAL

444
00:16:10,902 --> 00:16:11,202
DEPRESSION.

445
00:16:11,202 --> 00:16:12,069
OUR CROSS SECTIONAL STUDIES AND

446
00:16:12,069 --> 00:16:13,604
THOSE OF SEVERAL OTHER PEOPLE

447
00:16:13,604 --> 00:16:18,810
HAVE SHOWED THERE'S THOUGH

448
00:16:18,810 --> 00:16:19,777
BONAFIDE ENDOCRINE OPATHY, NO

449
00:16:19,777 --> 00:16:22,547
DEFICIENCY OR EXCESS OF ESTROGEN

450
00:16:22,547 --> 00:16:24,682
OR PROGESTERONE THAT

451
00:16:24,682 --> 00:16:26,083
DISTINGUISHES THESE WOMEN FROM

452
00:16:26,083 --> 00:16:27,819
REPRODUCTION FOR AGE AND MATCHED

453
00:16:27,819 --> 00:16:29,854
WOMAN WITHOUT DEPRESSION.

454
00:16:29,854 --> 00:16:31,956
AND THERE'S NO CHARACTERISTIC,

455
00:16:31,956 --> 00:16:34,091
INCLUDING HOT FLASHES THAT SEEM

456
00:16:34,091 --> 00:16:34,959
TO DISTINGUISH THIS GROUP.

457
00:16:34,959 --> 00:16:37,061
SO WE ASKED THE QUESTION IN OUR

458
00:16:37,061 --> 00:16:39,897
LONGITUDINAL STUDY, THIS IS DONE

459
00:16:39,897 --> 00:16:41,532
BY CONSTANT ZAO, A CLINICAL

460
00:16:41,532 --> 00:16:43,634
FELLOW IN THE BEHAVIORIAL

461
00:16:43,634 --> 00:16:44,902
ENDOKRENNOLOGY BRANCH AND SHE'S

462
00:16:44,902 --> 00:16:49,273
ANALYZED THIS DATA IN WHICH WE

463
00:16:49,273 --> 00:16:51,242
FOLLOWED PREMENOPAUSAL HEALTHY

464
00:16:51,242 --> 00:16:54,111
A-SYMPTOMATIC WOMEN, EVERY 6-8

465
00:16:54,111 --> 00:16:55,413
MONTHS, WE CONDUCTED VISITS

466
00:16:55,413 --> 00:16:56,647
DURING THE EARLY FOLLICULAR

467
00:16:56,647 --> 00:16:58,983
PHASE OF THE CYCLE UNTIL NAY

468
00:16:58,983 --> 00:17:00,651
WERE 6-12 MONTHS AFTER THE LAST

469
00:17:00,651 --> 00:17:01,552
MENSTRUAL PERIOD AND THIS WAS

470
00:17:01,552 --> 00:17:04,422
KIND OF A BEAR OF A STUDY.

471
00:17:04,422 --> 00:17:05,490
WE DID BLOOD HORMONE MEASURES

472
00:17:05,490 --> 00:17:09,760
AND I WILL BE FOCUSING ON FSH

473
00:17:09,760 --> 00:17:10,962
AND ESTRADISCIPLINARYOLE, AND

474
00:17:10,962 --> 00:17:12,196
PRELIMINARY DATA THAT CONSTANCE

475
00:17:12,196 --> 00:17:15,233
HAS ON THAT, AND PERFORMED

476
00:17:15,233 --> 00:17:16,200
DIAGNOSTIC INTERVIEWS IN ORDER

477
00:17:16,200 --> 00:17:17,502
TO EITHER CONFIRM THE PRESENCE

478
00:17:17,502 --> 00:17:19,403
OR ABSENCE OF THE DIN DROAM OF

479
00:17:19,403 --> 00:17:21,973
DEPRESSION AND IN SOME CASES

480
00:17:21,973 --> 00:17:24,909
BECAUSE IT'S PERSPECTIVELY

481
00:17:24,909 --> 00:17:26,444
MONITORED, THESE WOULD BE MINOR

482
00:17:26,444 --> 00:17:28,646
DEPRESSIONS, WE HAVE DAILY

483
00:17:28,646 --> 00:17:30,381
SYMPTOM RATINGS AS WELL AS

484
00:17:30,381 --> 00:17:31,582
CLINIC VISITS SO WE CAN

485
00:17:31,582 --> 00:17:33,050
UNDERSTAND THE PRODROAM.

486
00:17:33,050 --> 00:17:35,319
WE ALSO INCLAUDED A VARIETY OF

487
00:17:35,319 --> 00:17:37,088
MEASURES THAT HAD BEEN EITHER

488
00:17:37,088 --> 00:17:39,056
REPORTED TO ACCOMPANY DEPRESSION

489
00:17:39,056 --> 00:17:41,125
DURING MIDLIFE OR THE

490
00:17:41,125 --> 00:17:42,627
PERIMENOPAUSE AS WELL AS EVENTS

491
00:17:42,627 --> 00:17:47,198
THAT MIGHT CONTRIBUTE TO THE

492
00:17:47,198 --> 00:17:47,732
ONSET OF DEPRESSION.

493
00:17:47,732 --> 00:17:49,934
SO THIS IS A SPAGHETTI GRAPH OF

494
00:17:49,934 --> 00:17:52,436
THE 89 WOMEN WHO HAVE BEEN IN

495
00:17:52,436 --> 00:17:55,172
THIS STUDY THAT CONSTANCE IS

496
00:17:55,172 --> 00:17:57,441
ANALYZING, THE Y AXIS SHOWS THE

497
00:17:57,441 --> 00:17:59,176
NUMBER OF PARTICIPANTS.

498
00:17:59,176 --> 00:18:03,447
THE X-AXIS, THE LAST MENSTRUAL

499
00:18:03,447 --> 00:18:04,949
PERIOD IS MARKED BY THE DARK

500
00:18:04,949 --> 00:18:05,149
LINE.

501
00:18:05,149 --> 00:18:06,717
THE TIME BEFORE THAT ARE THE

502
00:18:06,717 --> 00:18:08,119
YEARS PRIOR TO THE LAST

503
00:18:08,119 --> 00:18:08,986
MENSTRUAL PERIOD AND THEN AFTER

504
00:18:08,986 --> 00:18:13,357
THAT ARE THE YEARS AFTER THE

505
00:18:13,357 --> 00:18:14,258
LAST MENSTRUAL PERIOD.

506
00:18:14,258 --> 00:18:16,894
EACH LINE WEP RESENTS A WOMEN'S

507
00:18:16,894 --> 00:18:20,197
COURSE THROUGH THE STUDY AND

508
00:18:20,197 --> 00:18:21,732
EACH DOTS REPRESENTS INDIVIDUAL

509
00:18:21,732 --> 00:18:23,834
CLINIC VISITS SO ON AVERAGE WE

510
00:18:23,834 --> 00:18:25,436
FOLLOWED EACH WOMAN FOR

511
00:18:25,436 --> 00:18:29,040
APPROXIMATELY 6 YEARS BUT

512
00:18:29,040 --> 00:18:31,375
CONSIDERABLY RAINCHL FROM 1-12.6

513
00:18:31,375 --> 00:18:35,713
YEARS, JUST TO FOCUS ON THE RED

514
00:18:35,713 --> 00:18:38,616
DOTS ARE THE WOMEN WHO REMAIN

515
00:18:38,616 --> 00:18:40,718
ASYMPTOMATIC DURING THE TRIAL

516
00:18:40,718 --> 00:18:42,620
AND BLUE DOTS ARE FOR THOSE WHO

517
00:18:42,620 --> 00:18:43,487
DEVELOP DEPRESSION AND WHEN WE

518
00:18:43,487 --> 00:18:45,656
FOUND IS A CLUSTERING OF

519
00:18:45,656 --> 00:18:46,090
DEPRESSIVE EPISODES.

520
00:18:46,090 --> 00:18:47,491
THESE ARE ALL THE EPISEDENTARYS

521
00:18:47,491 --> 00:18:48,793
OF DEPRESSION THAT OCCUR DURING

522
00:18:48,793 --> 00:18:51,429
THE TRIAL IN EACH OF THESE

523
00:18:51,429 --> 00:18:51,629
WOMEN.

524
00:18:51,629 --> 00:18:53,464
AND THERE WAS A CLUSTERING, THE

525
00:18:53,464 --> 00:18:55,866
Y-AXIS IS THE NUMBER OF

526
00:18:55,866 --> 00:18:57,702
DEPRESSIVE EPISODES IN THE

527
00:18:57,702 --> 00:19:01,973
AGAIN, IT'S PREAND POST LAST

528
00:19:01,973 --> 00:19:04,108
MENS, AND THIS IS OCCURRING

529
00:19:04,108 --> 00:19:06,777
DURING THE 24 MONTHS SURROUNDING

530
00:19:06,777 --> 00:19:08,312
THE LAST MENSTRUAL PERIOD AS

531
00:19:08,312 --> 00:19:09,914
WELL AS EPISODES THAT OCCURRED

532
00:19:09,914 --> 00:19:11,582
PRIOR TO THAT BUT WHAT WERE

533
00:19:11,582 --> 00:19:12,550
HIGHLIGHTED IN PINK ARE THE 1S

534
00:19:12,550 --> 00:19:15,586
THAT OCCURRED IN THE YEAR BEFORE

535
00:19:15,586 --> 00:19:18,022
OR AFTER THE LAST MENSTRUAL

536
00:19:18,022 --> 00:19:23,361
PERIOD. 

537
00:19:23,361 --> 00:19:24,795
AND WE IDENTIFIED 29 EPISODES IN

538
00:19:24,795 --> 00:19:25,296
22 WOMEN.

539
00:19:25,296 --> 00:19:27,665
WENT OF THESE OCCURRED IN THE 24

540
00:19:27,665 --> 00:19:28,833
MONTHS SURROUNDING THE LAST

541
00:19:28,833 --> 00:19:31,769
MENSTRUAL PERIOD AS A MENTIONED.

542
00:19:31,769 --> 00:19:35,406
IN 19 OF THESE 20 WOMEN THAT

543
00:19:35,406 --> 00:19:38,476
EVEN IF THEY DIDN'T OCCUR DURING

544
00:19:38,476 --> 00:19:40,678
THAT PERIOD OF THE 2 YEARS

545
00:19:40,678 --> 00:19:42,313
AROUND LAST MENSTRUAL PERIOD,

546
00:19:42,313 --> 00:19:45,149
THE EPISODE OF DEPRESSION

547
00:19:45,149 --> 00:19:48,819
OCCURRED AFTER WE IDENTIFIED AND

548
00:19:48,819 --> 00:19:51,022
ELVITTED PLASMA FSH LEVELS

549
00:19:51,022 --> 00:19:53,224
SUGGIESTING THAT THE

550
00:19:53,224 --> 00:19:54,058
REPRODUCKIVE AGING PROCESS

551
00:19:54,058 --> 00:19:57,495
PRESEED THE ONSET OF THE

552
00:19:57,495 --> 00:19:57,862
DEPRESSION.

553
00:19:57,862 --> 00:20:00,564
FINALLY, ONLY 4 WOMEN IN THIS

554
00:20:00,564 --> 00:20:02,633
COHORT HAD A PREVIOUS PATH MAJOR

555
00:20:02,633 --> 00:20:06,637
DEPRESSION, SO 18 OF THESE 22,

556
00:20:06,637 --> 00:20:08,939
WOMEN HAD A FIRST ONSET OF

557
00:20:08,939 --> 00:20:11,876
DEPRESSION IN THE PERIMENOPAUSE.

558
00:20:11,876 --> 00:20:14,445
SO LOOKING AT THEIR PLASMA

559
00:20:14,445 --> 00:20:15,012
ESTRADISCIPLINARYOLE LEVELS

560
00:20:15,012 --> 00:20:19,250
SHOWN IN THIS GRAPH AND I

561
00:20:19,250 --> 00:20:21,052
APOLOGIZE, THERE'S POTENTIAL

562
00:20:21,052 --> 00:20:22,019
CONFUSION WHERE THAL CASE, THE

563
00:20:22,019 --> 00:20:23,988
BLUE LINE ARE THE WOMEN WHO DID

564
00:20:23,988 --> 00:20:25,189
NOT EXPERIENCE DEPRESSION, SO

565
00:20:25,189 --> 00:20:27,825
THESE ARE--THESE ARE THE

566
00:20:27,825 --> 00:20:28,926
ASYMPTOMATEC WOMEN, THE RED LINE

567
00:20:28,926 --> 00:20:32,496
IS IN THIS CASE, THE WOMEN WHO

568
00:20:32,496 --> 00:20:33,998
DID DEVELOP DEPRESSION AND THIS

569
00:20:33,998 --> 00:20:36,367
SHOWS THE PATTERN OF

570
00:20:36,367 --> 00:20:37,668
ESTRADISCIPLINARYOLE SECRETION

571
00:20:37,668 --> 00:20:39,603
ALONG WITH 95% CONFIDENCE

572
00:20:39,603 --> 00:20:40,771
INTERVAL BAN OVER THE COURSE OF

573
00:20:40,771 --> 00:20:42,206
THE STUDY AND IT'S ANCHORED

574
00:20:42,206 --> 00:20:44,942
RELATIVE TO THE LAST MENSTRUAL

575
00:20:44,942 --> 00:20:45,176
PERIOD.

576
00:20:45,176 --> 00:20:50,381
AND WHAT WE FOUND IS SIGNIFICANT

577
00:20:50,381 --> 00:20:51,949
THESE PRELIMINARY DATA

578
00:20:51,949 --> 00:20:53,284
SUGGESTING IGF 95 CANT EFFECTS

579
00:20:53,284 --> 00:20:54,885
INTERACTION BETWEEN TIME AND THE

580
00:20:54,885 --> 00:20:56,387
ONSET OF DEPRESSION AND THAT

581
00:20:56,387 --> 00:20:57,455
THESE WERE DEMON TRAITED WITH

582
00:20:57,455 --> 00:21:00,057
THE WOMEN WHO DEVELOPED

583
00:21:00,057 --> 00:21:03,627
DEPRESSION HAD AN EARLIER PEAK

584
00:21:03,627 --> 00:21:04,995
DURING THE MENOPAUSE TRANSITION

585
00:21:04,995 --> 00:21:08,132
AND A HIGHER LEVEL OF

586
00:21:08,132 --> 00:21:09,366
ESTRADISCIPLINARYOLE SECRETION

587
00:21:09,366 --> 00:21:11,402
COMPARED WITH THE CONTROLS WHO

588
00:21:11,402 --> 00:21:15,005
PEAKED APPROXIMATELY A YEAR

589
00:21:15,005 --> 00:21:15,606
LATER.

590
00:21:15,606 --> 00:21:20,010
THIS IS HAPPENING, AGAIN,

591
00:21:20,010 --> 00:21:20,878
THOUGH, APPROXIMATELY 5-6 YEARS

592
00:21:20,878 --> 00:21:23,280
WHEREAS WE'RE SEEING THE

593
00:21:23,280 --> 00:21:25,182
CLUSTERING OF DEPRESSIVE

594
00:21:25,182 --> 00:21:26,851
EPISODES IN THE YEAR OR SO AFTER

595
00:21:26,851 --> 00:21:27,918
THE LAST MENSTRUAL PERIOD, SO

596
00:21:27,918 --> 00:21:29,186
THESE ARE THINGS THAT ARE

597
00:21:29,186 --> 00:21:30,921
HAPPENING BEFORE HAND THAT WE

598
00:21:30,921 --> 00:21:33,224
WOULDN'T CAPTURE IN OUR CLINIC

599
00:21:33,224 --> 00:21:35,292
WHEN WE'RE EVALUATING WOMEN

600
00:21:35,292 --> 00:21:36,327
CROSS SECTIONALLY.

601
00:21:36,327 --> 00:21:38,062
THE 2 LINES MEET ABOUT A YEAR

602
00:21:38,062 --> 00:21:40,664
BEFORE THE FINAL MENSTRUAL

603
00:21:40,664 --> 00:21:42,633
PERIOD AND BEGAN TO SEPARATE.

604
00:21:42,633 --> 00:21:44,235
SO THESE DATA SUGGEST A MORE

605
00:21:44,235 --> 00:21:46,604
EARLIER PEAK AND A MORE RAPID

606
00:21:46,604 --> 00:21:47,238
DECLINE OF ESTRADISCIPLINARYOLE

607
00:21:47,238 --> 00:21:49,640
IN THE WOMEN WHO DEVELOP

608
00:21:49,640 --> 00:21:50,941
DEPRESSION DURING THE

609
00:21:50,941 --> 00:21:52,209
PERIMENOPAUSE, THE FSH LEVELS

610
00:21:52,209 --> 00:21:54,879
SHOWING THE SAME SET UP WITH THE

611
00:21:54,879 --> 00:21:57,848
FSH, LEVELS AND THE 95%

612
00:21:57,848 --> 00:21:59,550
CONFIDENCE BANS FOR THE

613
00:21:59,550 --> 00:22:03,220
DEPRESSED WOMEN IN RED AND THE

614
00:22:03,220 --> 00:22:04,455
IEE, AUDIENCE SYMPTOMATIC WOMEN

615
00:22:04,455 --> 00:22:07,925
IN BLUE, THAT AGAIN, WE FOUND

616
00:22:07,925 --> 00:22:08,659
SIGNIFICANT EFFECTS OF

617
00:22:08,659 --> 00:22:10,227
INTERACTIONS BETWEEN TIME AND

618
00:22:10,227 --> 00:22:12,263
THE DIAGNOSIS OF DEPRESSION

619
00:22:12,263 --> 00:22:14,632
WHERE THERE WERE HIGHER FSH

620
00:22:14,632 --> 00:22:16,700
LEVELS, VERY EARLY ON IN THE

621
00:22:16,700 --> 00:22:18,402
MENOPAUSE TRANSITION, IN THE

622
00:22:18,402 --> 00:22:20,571
WOMEN WHO DEVELOP DEPRESSION AS

623
00:22:20,571 --> 00:22:22,907
WELL AS A STEEPER PEEK INCREASE

624
00:22:22,907 --> 00:22:26,043
THAT MAY CORRESPOND WITH THE

625
00:22:26,043 --> 00:22:27,945
MORE STEEPER DECLINE OF

626
00:22:27,945 --> 00:22:28,546
ESTRADISCIPLINARYOLE, REMEMBER

627
00:22:28,546 --> 00:22:29,914
THESE 2 HORMONES ARE KIND OF IN

628
00:22:29,914 --> 00:22:32,917
A LITTLE BIT OF A RECIPROCAL

629
00:22:32,917 --> 00:22:34,952
RELATIONSHIP WITH EACH OTHER

630
00:22:34,952 --> 00:22:36,954
PRIOR TO THE LAST MENSTRUAL

631
00:22:36,954 --> 00:22:38,622
PERIOD.

632
00:22:38,622 --> 00:22:40,691
SO, THESE DATA SUGGEST THAT ARE

633
00:22:40,691 --> 00:22:45,529
MAY ACTUALLY BE SOME HORMONAL

634
00:22:45,529 --> 00:22:47,932
ANTISEEDENTS OR ACCOMPANIMENTS

635
00:22:47,932 --> 00:22:48,599
OF PERIMENOPAUSAL DEPRESSION BUT

636
00:22:48,599 --> 00:22:50,334
MOST OF THEM ARE OCCURRING

637
00:22:50,334 --> 00:22:51,902
BEFORE THE ONSET OF DEPRESSION.

638
00:22:51,902 --> 00:22:55,005
SO THIS MAY BE SOMETHING THAT WE

639
00:22:55,005 --> 00:22:58,742
CAN, IF CONFIRMED IN THE FINAL

640
00:22:58,742 --> 00:23:00,110
DATA, MAY GIVE US SOME MEASURE

641
00:23:00,110 --> 00:23:02,279
OF WHAT MIGHT BE HAPPENING PRIOR

642
00:23:02,279 --> 00:23:04,148
TO I WOMAN EXPERIENCING

643
00:23:04,148 --> 00:23:05,416
DEPRESSION DURING THE MENOPAUSE

644
00:23:05,416 --> 00:23:07,484
TRANSITION THAT WILL GIVE US

645
00:23:07,484 --> 00:23:10,621
SOME MARKERS OF RISK.

646
00:23:10,621 --> 00:23:12,523
SO GOING BACK TO WHAT WE TALKED

647
00:23:12,523 --> 00:23:14,391
ABOUT, IS THAT THE MENOPAUSE

648
00:23:14,391 --> 00:23:17,595
TRANSITION, WE SEE THE EPISODES

649
00:23:17,595 --> 00:23:18,429
CLUSTER DURING THE LATE

650
00:23:18,429 --> 00:23:19,597
TRANSITION WHICH IS A TAME AS

651
00:23:19,597 --> 00:23:20,931
WELL AS SEVERAL OTHER STUDIES

652
00:23:20,931 --> 00:23:23,000
SHOWING THIS, THAT IT'S A TIME

653
00:23:23,000 --> 00:23:25,870
OF KIND OF THE MOST--THE

654
00:23:25,870 --> 00:23:27,571
GREATEST DECLINES IN ESTRO

655
00:23:27,571 --> 00:23:28,038
DISCIPLINARYOLE LEVEL.

656
00:23:28,038 --> 00:23:30,674
WE ALSO KNOW FROM SEVERAL

657
00:23:30,674 --> 00:23:32,810
STUDIES THAT

658
00:23:32,810 --> 00:23:35,613
ESTRADISCIPLINARYOLE MAY HAVE

659
00:23:35,613 --> 00:23:37,114
BOTH ACUTE ANTIDEPRESS ABT LIKE

660
00:23:37,114 --> 00:23:43,621
EFFECTS AS WELL AS PREVENTATIVE

661
00:23:43,621 --> 00:23:44,421
PERIMENOPAUSAL DEPRESSION

662
00:23:44,421 --> 00:23:47,291
SYMPTOMS AACCORDING TO A STUDY

663
00:23:47,291 --> 00:23:47,992
BY JENNIFER GORDON.

664
00:23:47,992 --> 00:23:51,428
SO WE ASKED WHETHER THIS

665
00:23:51,428 --> 00:23:52,129
PRECIPITATES DEPRESSION IN WOMEN

666
00:23:52,129 --> 00:23:54,632
WITH A HISTORY OF PAST

667
00:23:54,632 --> 00:23:54,932
DEPRESSION?

668
00:23:54,932 --> 00:23:57,501
SO THOSE WOMEN WE KNOW ARE

669
00:23:57,501 --> 00:23:58,202
VULNERABLE TO DEVELOPING

670
00:23:58,202 --> 00:23:59,436
DEPRESSION, WHAT ARE THE EFFECTS

671
00:23:59,436 --> 00:24:00,704
ON MOOD COMPARED TO WOMEN WHO

672
00:24:00,704 --> 00:24:02,239
DID NOT DEVELOP A DEPRESSION, SO

673
00:24:02,239 --> 00:24:03,874
THIS IS THE SCHEMATIC DESIGN OF

674
00:24:03,874 --> 00:24:06,543
THAT STUDY, WE RECRUITED WOMEN

675
00:24:06,543 --> 00:24:09,313
WHO HAD REPORTED ON HOW TO WELL

676
00:24:09,313 --> 00:24:11,315
CHARACTERIZE DEPRESSION DURING

677
00:24:11,315 --> 00:24:12,182
THE PERIMENOPAUSE.

678
00:24:12,182 --> 00:24:14,718
THEY WERE NOW POST MENOPAUSE AND

679
00:24:14,718 --> 00:24:16,120
HAD A REMISSION OF THE

680
00:24:16,120 --> 00:24:18,422
DEPRESSION OR IT STARTED SOME

681
00:24:18,422 --> 00:24:19,223
FORM OF THERAPY.

682
00:24:19,223 --> 00:24:20,758
THEY WERE TAKEN OFF THEIR

683
00:24:20,758 --> 00:24:23,260
CURRENT MEDS AND PLACED ON A

684
00:24:23,260 --> 00:24:24,428
STANDARD LEVEL OF

685
00:24:24,428 --> 00:24:26,163
ESTRADISCIPLINARYOLE AND A

686
00:24:26,163 --> 00:24:27,665
HUNDRED MICROGRAMS A DAY GIVEN

687
00:24:27,665 --> 00:24:29,767
BY SKIN PATCH FOR 3 WEEKS.

688
00:24:29,767 --> 00:24:31,835
AFTER 3 WEEKS, HALF THE GROUP

689
00:24:31,835 --> 00:24:34,905
CONTINUED ON THE SAME DOSE OF

690
00:24:34,905 --> 00:24:35,539
ESTRADISCIPLINARYOLE, WHAZ THE

691
00:24:35,539 --> 00:24:37,975
OTHER HALF OF THE WOMEN WERE

692
00:24:37,975 --> 00:24:40,311
CROSS TD OVER TO PLACEBO

693
00:24:40,311 --> 00:24:40,544
PATCHES.

694
00:24:40,544 --> 00:24:51,021
SO IF THERE WAS GOING TO BE

695
00:25:06,070 --> 00:25:08,739
EVIDENCE OF.

696
00:25:08,739 --> 00:25:11,809
--SO THEY EXPERIENCED BOTH THE

697
00:25:11,809 --> 00:25:13,377
SAME DOSES OF ESTRADIOL,

698
00:25:13,377 --> 00:25:14,845
PRESUMABLY HAD A CHANGE IN

699
00:25:14,845 --> 00:25:16,013
HORMONE MOANS IN THE 1 WHO IS

700
00:25:16,013 --> 00:25:17,047
WENT THROUGH THE WITHDRAWAL

701
00:25:17,047 --> 00:25:18,515
EMPLOY THIS IS AN EXAMPLE OF THE

702
00:25:18,515 --> 00:25:20,818
RESULTS WE SAW, THIS IS SCORES

703
00:25:20,818 --> 00:25:24,088
ON THE Y-AXIS OR THE CENTERS FOR

704
00:25:24,088 --> 00:25:24,822
EPIDEMIOLOGIC DEPRESSION STUDY

705
00:25:24,822 --> 00:25:26,423
SCALE WHERE HIGHER SCORES

706
00:25:26,423 --> 00:25:29,994
REPRESENT MORE SEVERE DEPRESSIVE

707
00:25:29,994 --> 00:25:30,427
SYMPTOMS.

708
00:25:30,427 --> 00:25:33,297
Y-AXIS EACH OF THESE BARS

709
00:25:33,297 --> 00:25:33,964
REPRESENT THE AVERAGE SCORE IN

710
00:25:33,964 --> 00:25:36,700
THE WOMEN WHO WERE IN THAT GROUP

711
00:25:36,700 --> 00:25:38,936
FOR EACH OF THEIR CLINIC VISITS

712
00:25:38,936 --> 00:25:40,704
DURING THE 6 WEEKS OF THE TRIAL.

713
00:25:40,704 --> 00:25:42,106
FOCUSING ON THE GROUP IN THE

714
00:25:42,106 --> 00:25:44,975
MIDDLE, THESE ARE THE WOMEN WITH

715
00:25:44,975 --> 00:25:50,014
PAST PERIMENOPAUSAL DEPRESSION

716
00:25:50,014 --> 00:25:54,485
WHO WHEN THEY WITHDREW

717
00:25:54,485 --> 00:25:58,589
EXPERIENCED RECURRENCE OF

718
00:25:58,589 --> 00:25:59,857
SYMPTOMS, IN CONTRAST TO THESE

719
00:25:59,857 --> 00:26:01,291
WOMEN WHO CONTINUE OFFICE OF

720
00:26:01,291 --> 00:26:01,859
DIVERSITY ESTRADISCIPLINARY

721
00:26:01,859 --> 00:26:03,994
OLDER PEOPLE BUT HAD THE SAME

722
00:26:03,994 --> 00:26:05,162
PAST HISTORY BUT COMPEARED TO

723
00:26:05,162 --> 00:26:06,530
THE CONTROL WOMEN WHEN

724
00:26:06,530 --> 00:26:07,131
EXPERIENCED NO SUBSTANTIAL

725
00:26:07,131 --> 00:26:09,867
CHANGE IN MOOD WHEN THEY

726
00:26:09,867 --> 00:26:13,037
UNDERWENT AN IDENTICAL HORMONE

727
00:26:13,037 --> 00:26:13,404
WITHDRAWAL.

728
00:26:13,404 --> 00:26:16,006
SO THESE DATA DOCUMENT THIS

729
00:26:16,006 --> 00:26:18,042
DIFFERENTIAL SENSITIVITY WE TALK

730
00:26:18,042 --> 00:26:19,443
ABOUT WHERE AND OTHERWISE IESHES

731
00:26:19,443 --> 00:26:22,880
DENTICAL CHANGE IN HORMONE WILL

732
00:26:22,880 --> 00:26:25,115
HAVE THE KASP A R PASQUANTINOITY

733
00:26:25,115 --> 00:26:26,617
OF INDUCING NEG5 MOOD STATES IN

734
00:26:26,617 --> 00:26:28,719
SOME WOMEN WHEN ARE OTHERWISE

735
00:26:28,719 --> 00:26:30,220
VULNERABILITY BUT NOT THE

736
00:26:30,220 --> 00:26:31,021
MAJORITY OF WOMEN.

737
00:26:31,021 --> 00:26:33,657
WE'RE PURSUING THIS QUESTION NOW

738
00:26:33,657 --> 00:26:37,728
IN A TRIAL, ASK WHETHER THE

739
00:26:37,728 --> 00:26:38,929
ASHINGS OF ESTROGEN WITHDRAWAL

740
00:26:38,929 --> 00:26:41,331
ARE MEDIATED BY E. R. BETA.

741
00:26:41,331 --> 00:26:43,434
SO WHY E. R. BETA.

742
00:26:43,434 --> 00:26:45,836
THIS WAS A SECOND ESTRAGENERATED

743
00:26:45,836 --> 00:26:49,273
THAT WAS CLONED BY CANNED WHAT,

744
00:26:49,273 --> 00:26:51,308
AND [INDISCERNIBLEA IN 1996 AT

745
00:26:51,308 --> 00:26:53,177
THE [INDISCERNIBLE].

746
00:26:53,177 --> 00:26:56,013
AND IT'S ENCODED ON A SEPARATE

747
00:26:56,013 --> 00:27:00,184
CHROMOSOME THAN THE ORIGINAL

748
00:27:00,184 --> 00:27:01,718
ER-ALPHA CHROMOSOME 6 AND 14

749
00:27:01,718 --> 00:27:03,954
RESPECTIVELY WITH 6 BEING FOR

750
00:27:03,954 --> 00:27:06,523
ER-ALPHA AND 14 FOR ER-BETA.

751
00:27:06,523 --> 00:27:11,161
SO THEY MAY BE UNDER DIFFERENT

752
00:27:11,161 --> 00:27:12,029
EVOLUTIONARY PRESSURES EMPLOY

753
00:27:12,029 --> 00:27:13,764
WHAT ER BETA IS OF INTEREST

754
00:27:13,764 --> 00:27:15,265
STHAT IT SEEMS TO BE MORE

755
00:27:15,265 --> 00:27:16,567
RELEVANT FOR SOME OF THE BRAIN

756
00:27:16,567 --> 00:27:19,603
AFFECTS THAT WE'RE LOOKING AT

757
00:27:19,603 --> 00:27:21,438
AND IT IS KIND DIFREPRESENTIALLY

758
00:27:21,438 --> 00:27:24,041
LOCALIZED IN THE BRAIN AND

759
00:27:24,041 --> 00:27:27,177
PREFRONTAL CORTEX, TEMPORAL

760
00:27:27,177 --> 00:27:30,414
LOBES, IT ALSO, IN AN STUDIES

761
00:27:30,414 --> 00:27:32,549
HAVE BEEN SHOWN TO MODEIATE THE

762
00:27:32,549 --> 00:27:34,051
EFFECTS OF ESTRADIOL ON A RANGE

763
00:27:34,051 --> 00:27:36,019
OF AFFECTIVE LIKE BEHAVIORS AS

764
00:27:36,019 --> 00:27:38,755
WELL AS REGULATING THE STRESS

765
00:27:38,755 --> 00:27:40,357
RESPONSE IN PARTICULARLY HPA

766
00:27:40,357 --> 00:27:41,525
ACCESS FUNCTION.

767
00:27:41,525 --> 00:27:43,360
SO WHEN WE THOUGHT WAS WHETHER

768
00:27:43,360 --> 00:27:46,363
WE KNOW THAT ER ALPHA PREVENTS

769
00:27:46,363 --> 00:27:47,131
THE WITHDRAWAL EFFECTS, WHAT WE

770
00:27:47,131 --> 00:27:50,767
WANT TO LOOK AT IS WHETHER

771
00:27:50,767 --> 00:27:52,302
SCHECT OFLY ER BETA MAY PREVENT

772
00:27:52,302 --> 00:27:54,104
THESE BECAUSE 1 OF THE THINGS IS

773
00:27:54,104 --> 00:27:55,339
SINCE THE WOMEN'S HEALTH

774
00:27:55,339 --> 00:27:56,940
INITIATIVE, THERE HAS BEEN A

775
00:27:56,940 --> 00:28:00,144
CONCERN AMONGST WOMEN AND THEIR

776
00:28:00,144 --> 00:28:01,745
GYNECOLOGISTS ABOUT USING

777
00:28:01,745 --> 00:28:03,680
ESTROGEN THERAPY ALTHOUGH THAT

778
00:28:03,680 --> 00:28:05,949
PENDULUM IS SWINGING BACK

779
00:28:05,949 --> 00:28:07,484
SOMEWHAT BUT CERTAINLY ER BETA

780
00:28:07,484 --> 00:28:08,819
COULD AFFORD A MORE TARGETED

781
00:28:08,819 --> 00:28:10,220
THERAPY ON SOME OF THE BRAIN

782
00:28:10,220 --> 00:28:13,991
CONDITIONS THAT WE'RE LOOKING AT

783
00:28:13,991 --> 00:28:16,160
WHETHER IT'S MOOD OR COGNITION,A

784
00:28:16,160 --> 00:28:18,795
WELL BECAUSE OF ITS LACK OF

785
00:28:18,795 --> 00:28:20,831
EFFECTS ON THE ENDOMETRIUM, ER

786
00:28:20,831 --> 00:28:23,167
BETA MAY HAVE A LONGER TERM

787
00:28:23,167 --> 00:28:25,736
SAFETY PROFILE THAN TYPICAL

788
00:28:25,736 --> 00:28:26,904
ESTROGEN THERAPY.

789
00:28:26,904 --> 00:28:29,439
SO THIS STUDY UNFORTUNATELY OR

790
00:28:29,439 --> 00:28:30,941
FORTUNATELY IS ALMOST FINERBED

791
00:28:30,941 --> 00:28:32,709
BUT NOT FINISHED AS OF YET.

792
00:28:32,709 --> 00:28:34,678
WE HAVE ABOUT 5 MORE WOMEN TO

793
00:28:34,678 --> 00:28:36,480
RECRUIT FOR THIS STUDY AND WHAT

794
00:28:36,480 --> 00:28:39,016
WE DO IS WE RECRUIT WOMEN

795
00:28:39,016 --> 00:28:43,854
SIMILAR TO THE ESTROGEN

796
00:28:43,854 --> 00:28:44,354
WITHDRAWAL STUDY.

797
00:28:44,354 --> 00:28:46,256
THEY ARE PLACED ON A STANDARD

798
00:28:46,256 --> 00:28:48,792
DOSE OF ESTRADIOL AND AFTER 3

799
00:28:48,792 --> 00:28:50,661
WEEKS, A THIRD OF THEM ARE

800
00:28:50,661 --> 00:28:52,129
CROSSED OVER TO PLACEBO WHICH

801
00:28:52,129 --> 00:28:52,796
WOULD BE THE WITHDRAWAL PERIOD

802
00:28:52,796 --> 00:28:54,731
AND THEN THE OTHER 2/3RDS

803
00:28:54,731 --> 00:28:57,601
RECEIVE 1 OF 2 DOSES OF THIS

804
00:28:57,601 --> 00:29:00,604
LYINTAIZ COMPOUND WHICH IS THE

805
00:29:00,604 --> 00:29:02,139
ESTROGEN RECEPTOR BETA AGONIST.

806
00:29:02,139 --> 00:29:05,108
WE USE 2 DIFFERENT DOSES TO BOTH

807
00:29:05,108 --> 00:29:07,744
LOOK AT IMPACT AND INCREASED

808
00:29:07,744 --> 00:29:09,479
PENETRATION TO THE BRAIN WHERE

809
00:29:09,479 --> 00:29:11,682
THAT'S BEEN A PROBLEM FOR SOME

810
00:29:11,682 --> 00:29:14,151
OF THE PREVIOUS ESTROGEN

811
00:29:14,151 --> 00:29:16,753
RECEPTOR AGONIST, IT COMPLICATES

812
00:29:16,753 --> 00:29:19,523
THINGS A LITTLE BIT BECAUSE THE

813
00:29:19,523 --> 00:29:21,825
OPTIMAL DOSE FOR SELECTIVITY FOR

814
00:29:21,825 --> 00:29:24,161
ER BETA VERSUS ER ALPHA IS AT

815
00:29:24,161 --> 00:29:25,262
LOWER DOSES SO WE HAVE TO

816
00:29:25,262 --> 00:29:26,897
INCLUDE A NUMBER OF THINGS WE'RE

817
00:29:26,897 --> 00:29:31,668
DOING IN COLLABORATION WITH ALAN

818
00:29:31,668 --> 00:29:33,604
[INDISCERNIBLE] TO MONITOR

819
00:29:33,604 --> 00:29:35,005
ER-ALPHA FEESKTS IN THESE WOMEN,

820
00:29:35,005 --> 00:29:39,343
SO WE CAN BE CERTAIN THAT WE CAN

821
00:29:39,343 --> 00:29:40,744
SAY PREDOMINANTLY, AND WHAT WE

822
00:29:40,744 --> 00:29:42,379
HAVE SEEN, IS THAT IN SOME OF

823
00:29:42,379 --> 00:29:45,882
OUR WOMEN, WE HAVE BEEN ABLE TO

824
00:29:45,882 --> 00:29:47,084
REPLICATE THE ESTRO GENERATED

825
00:29:47,084 --> 00:29:47,551
WITHDRAWAL.

826
00:29:47,551 --> 00:29:49,620
THESE ARE CSD SCORES SO THIS

827
00:29:49,620 --> 00:29:50,687
WOMEN FOR EXAMPLE, WHO MAY OR

828
00:29:50,687 --> 00:29:53,624
MAY NOT HAVE BEEN ON PLACEBO,

829
00:29:53,624 --> 00:29:56,727
BUT REGARDLESS, SHE DID

830
00:29:56,727 --> 00:29:59,062
EXPERIENCE A RECURRENCE OF HER

831
00:29:59,062 --> 00:30:00,897
MOOD SYMPTOMS OR IN THE CONTEXT

832
00:30:00,897 --> 00:30:01,932
OF THE DOUBLE BLIND.

833
00:30:01,932 --> 00:30:08,005
SO WE ARE AT LEAST ABLE TO DO

834
00:30:08,005 --> 00:30:09,373
THE--OR REPLICATE THE SIGNAL AND

835
00:30:09,373 --> 00:30:11,275
WE'RE HOPING NOW TO SEE THAT IN

836
00:30:11,275 --> 00:30:13,710
A COUPLE MONTHS WHAT THE EFFECTS

837
00:30:13,710 --> 00:30:17,314
OF ER-BETA MAY OR MAY NOT BE.

838
00:30:17,314 --> 00:30:19,883
SO IN THE LAST PART OF MY TALK I

839
00:30:19,883 --> 00:30:21,451
WANT TO FOCUS ON SOME OF OUR

840
00:30:21,451 --> 00:30:22,519
INVITRO STUDIES WE HAVE DONE TO

841
00:30:22,519 --> 00:30:24,921
ASK THE QUESTION ABOUT WHAT

842
00:30:24,921 --> 00:30:26,290
GIVES WITH THE DIFFERENCE

843
00:30:26,290 --> 00:30:28,959
BETWEEN THE WOMEN WITH PAST

844
00:30:28,959 --> 00:30:30,060
PERIMENOPAUSAL DEPRESSION WHO

845
00:30:30,060 --> 00:30:31,928
EXPERIENCE RECURRENCE AND THE

846
00:30:31,928 --> 00:30:34,531
CONTROLS WHO ARE OTHERWISE

847
00:30:34,531 --> 00:30:35,832
IDENTICAL EXCEPT THEY DID NOT

848
00:30:35,832 --> 00:30:38,702
HAVE A HISTORY OF DEPRESSION

849
00:30:38,702 --> 00:30:39,836
EITHER DURING THE PERIMENOPAUSE

850
00:30:39,836 --> 00:30:41,605
OR AT ANY OTHER TIME IN THEIR

851
00:30:41,605 --> 00:30:43,240
LIFE, SO THIS IS WORK THAT'S

852
00:30:43,240 --> 00:30:44,508
DONE IN COLLABORATION, THIS IS

853
00:30:44,508 --> 00:30:47,911
WORK DONE BY SARAH

854
00:30:47,911 --> 00:30:48,845
[INDISCERNIBLE], A FELLOW IN OUR

855
00:30:48,845 --> 00:30:50,614
GROUP AS WELL AS IN

856
00:30:50,614 --> 00:30:52,749
COLLABORATION WITH DAVID GOLDMAN

857
00:30:52,749 --> 00:30:55,752
AT THE LAB OF NEUROGENETICS AT

858
00:30:55,752 --> 00:30:55,952
NIAAA.

859
00:30:55,952 --> 00:30:59,656
AND WHAT WE WANTED TO ASK WAS

860
00:30:59,656 --> 00:31:00,957
GIVEN THAT STEROIDS ACT THROUGH

861
00:31:00,957 --> 00:31:01,758
THE NUCLEAR MEMORY RESPONSE

862
00:31:01,758 --> 00:31:03,293
BREAN IN LARGE PART IS WHETHER

863
00:31:03,293 --> 00:31:06,697
THERE'S A DRVES IN THE CELLULAR

864
00:31:06,697 --> 00:31:08,198
MECHANISM UNDERLYING THIS

865
00:31:08,198 --> 00:31:10,300
DIFFERENTIAL BEHAVIOR RESPONSE

866
00:31:10,300 --> 00:31:11,635
TO ESTROGEN WITHDRAWAL.

867
00:31:11,635 --> 00:31:14,771
SO WHAT SARAH DID WAS TRY TO

868
00:31:14,771 --> 00:31:16,273
RECAPITULATE THE CLINICAL SPRMS

869
00:31:16,273 --> 00:31:17,674
THAT WE'RE DOING IN THESE WOMEN

870
00:31:17,674 --> 00:31:21,011
BY TAKING CELLS FROM THEM AND

871
00:31:21,011 --> 00:31:23,714
TRYING TO EXPOSE THEM TO

872
00:31:23,714 --> 00:31:25,015
ESTROGEN OR ESTROGEN WITHDRAWAL.

873
00:31:25,015 --> 00:31:27,317
SO WE RECRUITED IN THE FIRST

874
00:31:27,317 --> 00:31:28,618
COHORT, WE RECRUITED WOMEN WHO

875
00:31:28,618 --> 00:31:30,587
WERE SERVED AS CONTROLS IN THE

876
00:31:30,587 --> 00:31:32,155
ESTARE GEN WITHDRAWAL STUDY, OR

877
00:31:32,155 --> 00:31:33,990
WERE IN THE PERIMENOPAUSAL

878
00:31:33,990 --> 00:31:36,626
DEPRESSION GROUP, AND WHO SHOWED

879
00:31:36,626 --> 00:31:39,162
THE PHENOTYPE OF A RECURRENCE OF

880
00:31:39,162 --> 00:31:41,064
THEIR MOOD SYMPTOMS DURING

881
00:31:41,064 --> 00:31:41,832
ESTROGEN WITHDRAWAL.

882
00:31:41,832 --> 00:31:44,000
NOW THE FIRST QUESTION WAS TO

883
00:31:44,000 --> 00:31:47,337
SEE SARAH DID PATIENT DERIVED

884
00:31:47,337 --> 00:31:50,640
LYMPHBLASTOID CELL LINES THAT

885
00:31:50,640 --> 00:31:51,441
ARE EPSTEIN BARR-INFECKED AND

886
00:31:51,441 --> 00:31:53,643
THEY ARE KIND OF OLD LYMPHOCYTES

887
00:31:53,643 --> 00:31:56,546
TO THE A LOT OF THE INITIAL

888
00:31:56,546 --> 00:31:57,714
METHYLATION MARKS AND MARKERS

889
00:31:57,714 --> 00:32:02,219
RELATED TO ENVIRONMENT OR OTHER

890
00:32:02,219 --> 00:32:03,320
FACTORS ARE WASHED OUT AND

891
00:32:03,320 --> 00:32:05,822
THERE'S JUST LEFT THE GENETIC

892
00:32:05,822 --> 00:32:08,892
CONSTITUENTS AND WE WANTED TO

893
00:32:08,892 --> 00:32:10,293
SEE WHETHER THESE CELLS ACTUALLY

894
00:32:10,293 --> 00:32:13,263
HAD THE MACHINERY TO COMMUNICATE

895
00:32:13,263 --> 00:32:15,699
WITH SEX STEROIDS SO WE

896
00:32:15,699 --> 00:32:17,267
DID--SARAH SHOWED THAT

897
00:32:17,267 --> 00:32:19,603
THESE--MOST OF THE SEX STEROID

898
00:32:19,603 --> 00:32:20,804
RECEPTORS WERE PRESENT BOTH IN

899
00:32:20,804 --> 00:32:23,039
MESSAGE AND IN PROTEIN.

900
00:32:23,039 --> 00:32:24,908
SO, THEN WHAT WHEY DID IS SHE

901
00:32:24,908 --> 00:32:27,210
SET UP EACH CELL LINE, WOULD BE

902
00:32:27,210 --> 00:32:33,150
EXPOSED TO A VEHICLE, I THINK

903
00:32:33,150 --> 00:32:35,152
JUST AS THE CONTROL ESTRADIOL

904
00:32:35,152 --> 00:32:42,826
EXPOSURE IN THE CELL SCULTURE OR

905
00:32:42,826 --> 00:32:43,727
ESTRA-DIAL EXPOSURE FOLLOWED BY

906
00:32:43,727 --> 00:32:46,630
CHANGE TO VEHICLE WHICH WOULD BE

907
00:32:46,630 --> 00:32:47,664
THE ESTRADIOL CONTROL GROUP ASK

908
00:32:47,664 --> 00:32:50,300
WE DID THAT WITH BOTH THE

909
00:32:50,300 --> 00:32:53,503
CONTROLS AS WELL ASLET

910
00:32:53,503 --> 00:32:53,970
PERIMENOPAUSAL GROUP.

911
00:32:53,970 --> 00:32:56,907
AND THEN WE HAD A SMALL COHORT

912
00:32:56,907 --> 00:32:59,910
WHICH WAS RECRUITED ABOUT YOU

913
00:32:59,910 --> 00:33:03,013
HAD A PHENOTYPE, SHE PERFORMED

914
00:33:03,013 --> 00:33:04,181
WHOLE TRANSCRIPTOME SEQUENCING

915
00:33:04,181 --> 00:33:05,982
AS WELL AS DIFFERENTIAL GENE

916
00:33:05,982 --> 00:33:08,752
EXPRESSION AND A PATHWAY NETWORK

917
00:33:08,752 --> 00:33:09,019
ANALYSIS.

918
00:33:09,019 --> 00:33:10,887
IN THE SECOND COHORT WHICH WAS A

919
00:33:10,887 --> 00:33:12,489
BROADER COHORT I THINK OF 18

920
00:33:12,489 --> 00:33:15,058
WOMEN WHO MET CRITERIA FOR

921
00:33:15,058 --> 00:33:15,659
MENOPAUSAL DEPRESSION AND 21

922
00:33:15,659 --> 00:33:18,128
CONTROLS WHO DID FOCUS ON THE

923
00:33:18,128 --> 00:33:18,929
HAVE PERIMENOPAUSAL DEPRESSION,

924
00:33:18,929 --> 00:33:21,665
SHE USED A DIFFERENT TECHNIQUE

925
00:33:21,665 --> 00:33:25,969
TO CONFIRM THE GENE EXPRESSION

926
00:33:25,969 --> 00:33:26,903
IN THAT GROUP.

927
00:33:26,903 --> 00:33:29,339
SO 2 GENES APPEAR THAD WERE OF

928
00:33:29,339 --> 00:33:30,707
BIOLOGICAL INTEREST THAT WERE

929
00:33:30,707 --> 00:33:34,110
ALSO KIND OF SEX STEROID

930
00:33:34,110 --> 00:33:34,811
RELATED, WERE SIGNIFICANT,

931
00:33:34,811 --> 00:33:35,645
DIFFERENT BETWEEN CONTROLS AND

932
00:33:35,645 --> 00:33:37,481
PATIENTS AND THAT HAD SOME

933
00:33:37,481 --> 00:33:42,185
POETIC TEBTIAL RELEVANCE FOR

934
00:33:42,185 --> 00:33:43,253
AFFECTIVE SYNDROMES.

935
00:33:43,253 --> 00:33:46,590
ONE OF THEM IS CXCL 10 WHICH IS

936
00:33:46,590 --> 00:33:48,225
A CHEMOKINE.

937
00:33:48,225 --> 00:33:49,159
PROINFLMATORY.

938
00:33:49,159 --> 00:33:52,329
IT'S ALSO CALLED IP 10, AND

939
00:33:52,329 --> 00:33:54,431
WHAT'S INTERESTING GIVEN OUR

940
00:33:54,431 --> 00:33:56,900
KIND OF EPIDEMIOLOGIC STUDIES

941
00:33:56,900 --> 00:33:57,934
THAT DISASSOCIATION BETWEEN

942
00:33:57,934 --> 00:34:00,604
HEART DEC AND DEPRESSION DURING

943
00:34:00,604 --> 00:34:02,138
PERIAND POST MENOPAUSE THAT IT

944
00:34:02,138 --> 00:34:04,975
HAS BEEN IDENTIFIED BY THE

945
00:34:04,975 --> 00:34:07,911
CLINICAL BIOMARKER FOR HEART

946
00:34:07,911 --> 00:34:09,746
FAILURE AND LEFT VENTRICULAR

947
00:34:09,746 --> 00:34:10,046
DYSFUNCTION.

948
00:34:10,046 --> 00:34:12,883
AGAIN IT IS POTENTIALLY OF

949
00:34:12,883 --> 00:34:13,884
INTEREST GIIVE THIS

950
00:34:13,884 --> 00:34:17,787
EPIDEMIOLOGIC FINDINGS OF THE

951
00:34:17,787 --> 00:34:19,689
INCREASED CARDIAC MORTALITY IN

952
00:34:19,689 --> 00:34:21,725
PERIMENOPAUSAL DEPRESSION EMPLOY

953
00:34:21,725 --> 00:34:25,896
SO WHAT SARAH FOUND IS THE HOT

954
00:34:25,896 --> 00:34:27,664
OR WHY-AXIS OF THESE KILOBASE, I

955
00:34:27,664 --> 00:34:28,765
CAN'T REMEMBER THE M BUT IF YOU

956
00:34:28,765 --> 00:34:31,668
NEED TO KNOW I CAN ASK SARAH,

957
00:34:31,668 --> 00:34:34,304
THAT SHE FOUND THAT YOU KNOW A

958
00:34:34,304 --> 00:34:35,572
HIGHER EXPRESSION IS ASSOCIATED

959
00:34:35,572 --> 00:34:37,407
WITH THE HIGHER VALUEOT Y-AXIS,

960
00:34:37,407 --> 00:34:39,809
AND THESE ARE THE CONTROL

961
00:34:39,809 --> 00:34:41,011
VALUES, DURING THE 3 HORMONE

962
00:34:41,011 --> 00:34:43,179
CONDITIONS AND THESE ARE THE

963
00:34:43,179 --> 00:34:45,649
VALUES FOR THE WOMEN WITH

964
00:34:45,649 --> 00:34:46,583
PERIMENOPAUSAL DEPRESSION AND

965
00:34:46,583 --> 00:34:49,586
YOU SEE DURING THE ESTRADIOL

966
00:34:49,586 --> 00:34:50,320
WITHDRAWAL PHASE, THIS HISTOGRAM

967
00:34:50,320 --> 00:34:51,955
HERE THAT THERE WAS A

968
00:34:51,955 --> 00:34:53,189
SIGNIFICANT INCREASE IN THE

969
00:34:53,189 --> 00:34:55,959
EXPRESSION FOR THE YEEN FOR CXCL

970
00:34:55,959 --> 00:34:56,192
10.

971
00:34:56,192 --> 00:34:59,396
SHE THEN USED IN THE SECOND

972
00:34:59,396 --> 00:35:01,932
COHORT, A LARGER COHORT WITH A

973
00:35:01,932 --> 00:35:03,600
BROADER FEIGNY TYPE, SHE USED PC

974
00:35:03,600 --> 00:35:06,903
R TO CONFIRM THE INCREASED

975
00:35:06,903 --> 00:35:07,871
EXPRESSION OF CXCL 10 AND SHE

976
00:35:07,871 --> 00:35:09,506
ALSO LOOKED TO SEA WHETHER THERE

977
00:35:09,506 --> 00:35:13,510
WAS AN INCREASED EXPRESSION IN

978
00:35:13,510 --> 00:35:16,646
THE CXCL 10 PROTEIN USING AN

979
00:35:16,646 --> 00:35:18,815
ELIZA ASSAY WHICH SHOWED IN THE

980
00:35:18,815 --> 00:35:20,584
MEDIA OF THESE CELLS, NOT IN THE

981
00:35:20,584 --> 00:35:22,819
CONTROLS BUT IN THE PATES, THERE

982
00:35:22,819 --> 00:35:23,653
WAS INCREASED EXPRESSION OF THE

983
00:35:23,653 --> 00:35:25,155
PROTEIN EMPLOY SO THAT'S

984
00:35:25,155 --> 00:35:26,990
SOMETHING WE'RE GOING TO LOOK

985
00:35:26,990 --> 00:35:29,993
FURRINGER IN OUR STUDY IN OUR

986
00:35:29,993 --> 00:35:30,627
LONGITUDINAL STUDY, THE SECOND

987
00:35:30,627 --> 00:35:35,031
YEEN WAS A YEEN THAT ENCODES THE

988
00:35:35,031 --> 00:35:37,601
CYTOCHROME P457 B 1 STEROID

989
00:35:37,601 --> 00:35:38,335
METABOLIC HORMONE, ACTUALLY

990
00:35:38,335 --> 00:35:41,638
INVOLVED IN THE METABOLISM OF

991
00:35:41,638 --> 00:35:43,640
PREGMEANA LEAN AND DATA, IT'S

992
00:35:43,640 --> 00:35:45,842
THE MAJOR ROOT FOR THE EXCRETION

993
00:35:45,842 --> 00:35:47,811
OF THESE 2 HORMONES BOTH OF

994
00:35:47,811 --> 00:35:50,680
WHICH ARE MIEWR O STEROIDS AND

995
00:35:50,680 --> 00:35:53,783
IT IS INTERESTING THAT 7 HYDROXY

996
00:35:53,783 --> 00:35:55,552
EHDA IS A BETA AGONIST SO THE

997
00:35:55,552 --> 00:35:59,923
INCREASE IN THAT COULD  REFLECT

998
00:35:59,923 --> 00:36:01,191
SOME TYPE OF HOMEOSTATIC

999
00:36:01,191 --> 00:36:03,326
MECHANISM IN WOMEN WITH

1000
00:36:03,326 --> 00:36:03,994
PERIMENOPAUSAL DEPRESSION EMPLOY

1001
00:36:03,994 --> 00:36:08,398
WHAT WE FOUND HERE AGAIN,

1002
00:36:08,398 --> 00:36:09,366
SIMILAR CONSTRUCT TO THE SLIDE,

1003
00:36:09,366 --> 00:36:12,702
IN THE WOMEN WITH PERIMENOPAUSAL

1004
00:36:12,702 --> 00:36:13,903
DEPRESSION ACROSS ALL 3 HORMONE

1005
00:36:13,903 --> 00:36:16,439
CONDITIONS SO THIS IS MORE OF A

1006
00:36:16,439 --> 00:36:19,175
STRAIGHT MARKER RATHER THAN

1007
00:36:19,175 --> 00:36:20,677
SOMETHING RELATED TO ESTROGEN

1008
00:36:20,677 --> 00:36:22,178
WITHDRAWAL THAT THERE WAS AN

1009
00:36:22,178 --> 00:36:23,913
INCREASED EXPRESSION OF THIS

1010
00:36:23,913 --> 00:36:24,381
GENE.

1011
00:36:24,381 --> 00:36:27,017
THAT WAS CONFIRMED IN THE

1012
00:36:27,017 --> 00:36:28,752
BROADER PHENOTYPE BY PC R, AND

1013
00:36:28,752 --> 00:36:31,454
THAT ALSO WHEN WE TOOK--ADD THE

1014
00:36:31,454 --> 00:36:32,822
HORMONE LEVELS FOR THE WOMEN

1015
00:36:32,822 --> 00:36:34,124
THAT PARTICIPATE INDEED THIS

1016
00:36:34,124 --> 00:36:36,726
STUDY, IN THE LARGER PHENOTYPE,

1017
00:36:36,726 --> 00:36:39,429
THAT THE EXPRESSION OF THIS GENE

1018
00:36:39,429 --> 00:36:43,633
CORRELATED WITH DHEA LEVELS IN

1019
00:36:43,633 --> 00:36:44,401
THOSE WOMEN.

1020
00:36:44,401 --> 00:36:47,871
SO AGAIN IT'S GOT BIOLOGICAL

1021
00:36:47,871 --> 00:36:51,675
RELEVANCE AND WE HOPE TO BE

1022
00:36:51,675 --> 00:36:54,310
LOOKING AT IN CONSTANTS THE

1023
00:36:54,310 --> 00:36:55,145
LONGITUDINAL STUDY, BOTH THE

1024
00:36:55,145 --> 00:36:58,448
CHANGE IN THESE INFLAMMATORY

1025
00:36:58,448 --> 00:37:00,183
MARKERSA WELL AS THESE HORMONES

1026
00:37:00,183 --> 00:37:03,553
THAT MIGHT BE ALTERED BY AN

1027
00:37:03,553 --> 00:37:05,321
ALERATION IN THE SIP 7 B1.

1028
00:37:05,321 --> 00:37:10,860
SO IN SUMMARY THEN, THESE DATA

1029
00:37:10,860 --> 00:37:13,763
SUGGEST THAT INCREASED CXCL10

1030
00:37:13,763 --> 00:37:18,168
BEING BE A RISK FACTOR FOR BOTH

1031
00:37:18,168 --> 00:37:19,969
PERIMENOPAUSAL DEPRESSION AND

1032
00:37:19,969 --> 00:37:21,705
CARDIOVASCULAR DISEASE

1033
00:37:21,705 --> 00:37:24,774
CONSISTENT WITH JENNIFER

1034
00:37:24,774 --> 00:37:27,343
GLORDON'S WORK SHOWING THAT IT

1035
00:37:27,343 --> 00:37:28,178
PREVENTED PERIMENOPAUSAL

1036
00:37:28,178 --> 00:37:29,512
DEPRESSION AND PREVENTED HEART

1037
00:37:29,512 --> 00:37:31,114
DISEASE ALTHOUGH THIS IS

1038
00:37:31,114 --> 00:37:31,848
CONTROVERSIAL.

1039
00:37:31,848 --> 00:37:35,318
IT ALSO COULD SUGGIEST THAT THE

1040
00:37:35,318 --> 00:37:36,853
BENEFITS OF ESTRADIOL THERAPY

1041
00:37:36,853 --> 00:37:38,655
FOR DEPRESSION AND

1042
00:37:38,655 --> 00:37:39,389
CARDIOVASCULAR INDICATIONS IN

1043
00:37:39,389 --> 00:37:41,891
SOME WOMEN, AGAIN THIS, IS A

1044
00:37:41,891 --> 00:37:45,195
SUBGROUP OF WOMEN, THE MAJORITY

1045
00:37:45,195 --> 00:37:47,497
OF WOMEN GO THROUGH

1046
00:37:47,497 --> 00:37:48,331
PERIMENOPAUSE WITHOUT ANY

1047
00:37:48,331 --> 00:37:51,267
EPISODES OF DEPRESSION BUT IT

1048
00:37:51,267 --> 00:37:53,470
COULD SERVE AS 1 POTENTIAL

1049
00:37:53,470 --> 00:37:55,004
EXPLANATION ALTHOUGH THERE ARE

1050
00:37:55,004 --> 00:37:57,140
MANY FOR THE DISCORDANT

1051
00:37:57,140 --> 00:37:58,074
RESULTINGS FOR OBSERVATIONAL

1052
00:37:58,074 --> 00:37:59,609
STUDIES LOOKINGA THE HORMONE

1053
00:37:59,609 --> 00:38:01,077
EFFECTS OF THERAPY IN WOMEN AND

1054
00:38:01,077 --> 00:38:03,113
NEGATIVE FINDINGS OF THE

1055
00:38:03,113 --> 00:38:04,380
WEMENT'S HEALTH INITIATIVE.

1056
00:38:04,380 --> 00:38:06,216
FINALLY IT SUGGESTS THAT THE

1057
00:38:06,216 --> 00:38:08,318
ROLE OF NEUROSTEROIDS IN

1058
00:38:08,318 --> 00:38:09,085
PERIMENOPAUSAL DEPRESSION AND

1059
00:38:09,085 --> 00:38:10,887
THERE IS 1 TRIAL ONGOING DOWN AT

1060
00:38:10,887 --> 00:38:13,423
THE UNIVERSITY OF SOUTHWEST IN

1061
00:38:13,423 --> 00:38:18,695
TEXAS LOOKINGA THE EFFECTS OF

1062
00:38:18,695 --> 00:38:20,029
PREGNENOLONE AS A TREME FOR

1063
00:38:20,029 --> 00:38:20,430
THESE WOMEN.

1064
00:38:20,430 --> 00:38:22,031
IF I HAVE A FEW MINUTES WHICH I

1065
00:38:22,031 --> 00:38:27,070
DO, I WANT TO GO THROUGH

1066
00:38:27,070 --> 00:38:29,672
PRELIMINARY OTHERWISE LESS

1067
00:38:29,672 --> 00:38:31,174
VETTED MATERIAL THAT

1068
00:38:31,174 --> 00:38:32,876
DR. [INDISCERNIBLE] HAS FOUND

1069
00:38:32,876 --> 00:38:33,143
RECENTLY.

1070
00:38:33,143 --> 00:38:36,346
AND WHAT SHE DID WAS EMPLOY A

1071
00:38:36,346 --> 00:38:38,214
DATA-DRIVEN APPROACH RATHER THAN

1072
00:38:38,214 --> 00:38:40,750
LITERATURE BASED ON APPROACH TO

1073
00:38:40,750 --> 00:38:43,052
LOOKING AT KIND OF GENE NETWORKS

1074
00:38:43,052 --> 00:38:46,089
AND HUB YEENS THAT MAY ALSO BE

1075
00:38:46,089 --> 00:38:46,990
RELEVANT IN PERIMENOPAUSAL

1076
00:38:46,990 --> 00:38:49,359
DEPRESSION AND THIS IS A CLUSTER

1077
00:38:49,359 --> 00:38:51,561
DENDRITIC CELL ROUGH ATOM GRAM

1078
00:38:51,561 --> 00:38:52,529
WHICH SHOWS DRVESS IN GENE

1079
00:38:52,529 --> 00:38:53,930
EXPRESSION THAT ARE HIGHLY

1080
00:38:53,930 --> 00:39:00,170
CORRELATED WITH EACH OTHER, AND

1081
00:39:00,170 --> 00:39:03,740
THEY THEN DEFINE THESE CLUSTERS

1082
00:39:03,740 --> 00:39:05,208
OF OTHERWISE CORRELATED GENES

1083
00:39:05,208 --> 00:39:07,710
AND WE'LL FIND IN THE MOST

1084
00:39:07,710 --> 00:39:09,345
HEAVILY CORRELATED GENE HUB OR A

1085
00:39:09,345 --> 00:39:11,047
HUB FOR THAT CLUSTER.

1086
00:39:11,047 --> 00:39:12,582
AND THEN THESE ARE THEN

1087
00:39:12,582 --> 00:39:15,351
PROCESSED WITH RESPECT TO THEIR

1088
00:39:15,351 --> 00:39:20,623
CORRELATIONS IN A VERY LARGE

1089
00:39:20,623 --> 00:39:21,524
MATRIX, MULTIPLE MATRIXES

1090
00:39:21,524 --> 00:39:23,092
SIMILAR TO WHAT'S BEEN DONE IN

1091
00:39:23,092 --> 00:39:25,295
THE BRAIN IMAGING STUDIES WITH

1092
00:39:25,295 --> 00:39:26,462
RESTINGITATE TO IDENTIFY

1093
00:39:26,462 --> 00:39:28,031
DIFFERENCES EITHER BETWEEN

1094
00:39:28,031 --> 00:39:30,767
PATIENTS AND CONTROLS OR BETWEEN

1095
00:39:30,767 --> 00:39:32,802
KIND OF ESTRO GENERATED

1096
00:39:32,802 --> 00:39:34,504
WITHDRAWAL AND ESTRO GENERATED

1097
00:39:34,504 --> 00:39:35,705
THERAPY AND THEN THOSE DEFENSES

1098
00:39:35,705 --> 00:39:37,240
ARE MAPPED ON TO BASED ON

1099
00:39:37,240 --> 00:39:39,309
LITERATURE OF KIND OF AREAS OF

1100
00:39:39,309 --> 00:39:40,343
GENE EXPRESSION THAT ARE

1101
00:39:40,343 --> 00:39:42,812
RELEVANT FOR A VARIETY OF

1102
00:39:42,812 --> 00:39:44,113
BIOLOGICAL PROCESSES, AND WHAT

1103
00:39:44,113 --> 00:39:46,282
SARAH HAS DONE THEN WITH THIS

1104
00:39:46,282 --> 00:39:50,019
DATA DRIVEN APPROACH IS

1105
00:39:50,019 --> 00:39:51,721
IDENTIFIED SEVERAL MODULES THAT

1106
00:39:51,721 --> 00:39:54,490
ARE RELEVANT FOR EITHER ESTROGEN

1107
00:39:54,490 --> 00:39:55,959
WITHDRAWAL OR FOR PERIMENOPAUSAL

1108
00:39:55,959 --> 00:39:57,660
DEPRESSION AND 1 OF THEM IS

1109
00:39:57,660 --> 00:40:00,163
RELATED TO THIS MIDNIGHT BLUE

1110
00:40:00,163 --> 00:40:02,298
MODULE WHICH IS WHEN WE LOOK AT

1111
00:40:02,298 --> 00:40:06,870
IT, IS 1 OF THE HUB GENES IS THE

1112
00:40:06,870 --> 00:40:08,738
PER 1 GENE WHICH MANY OF YOU

1113
00:40:08,738 --> 00:40:13,309
KNOW IS VERY RELEVANT FOR

1114
00:40:13,309 --> 00:40:14,210
GENERATING CIRCADIAN RHYTHMS, IT

1115
00:40:14,210 --> 00:40:18,381
MAY SPEAK TO SOME OF THE SLEEP

1116
00:40:18,381 --> 00:40:19,949
ISSUES THAT ARE PRESENT AND HAVE

1117
00:40:19,949 --> 00:40:21,584
BEEN IDENTIFIED DURING THE

1118
00:40:21,584 --> 00:40:26,022
PERIMENOPAUSE OR IN THE CONTEXT

1119
00:40:26,022 --> 00:40:26,723
OF PERIMENOPAUSAL DEPRESSION AND

1120
00:40:26,723 --> 00:40:29,259
ALSO MAY HELP US GIVE US A CLUE

1121
00:40:29,259 --> 00:40:31,127
AS TO WHAT MIGHT BE UNDERLYING

1122
00:40:31,127 --> 00:40:33,563
SOME OF THESE OR PUT AT A RISK

1123
00:40:33,563 --> 00:40:37,100
FACTOR FOR SOME OF THESE

1124
00:40:37,100 --> 00:40:37,500
CONDITIONS.

1125
00:40:37,500 --> 00:40:40,036
A SECOND GENE IS IN THIS OTHER

1126
00:40:40,036 --> 00:40:41,971
MODULE, THE DARK ORANGE WHICH

1127
00:40:41,971 --> 00:40:45,008
CONTAINS THE HUB GENE FOR

1128
00:40:45,008 --> 00:40:46,175
CXCL10, THE CYTOKINE I TALKED

1129
00:40:46,175 --> 00:40:48,044
ABOUT THAT SHE HAD IDENTIFIED

1130
00:40:48,044 --> 00:40:50,346
EARLIER BUT ALSO WHEN SARAH

1131
00:40:50,346 --> 00:40:52,215
COMPARED THIS WITH THE UK

1132
00:40:52,215 --> 00:40:55,485
BIOBANK THAT IT KIND OF

1133
00:40:55,485 --> 00:40:56,653
OVERLAPPED WITH WITH STUDIES IN

1134
00:40:56,653 --> 00:41:00,323
WOMEN WITH AN EARLIER AGENT OF

1135
00:41:00,323 --> 00:41:02,859
MENOPAUSE AND I KNOW THIS' A

1136
00:41:02,859 --> 00:41:04,260
CURRENT STUDY, HOWARD LEE IS

1137
00:41:04,260 --> 00:41:09,032
LOOKING AT THIS DATA IN WOMEN

1138
00:41:09,032 --> 00:41:10,934
WITH PREMATURE OVARIAN

1139
00:41:10,934 --> 00:41:13,069
INSUFFICIENCY, THERE HAS BEEN IN

1140
00:41:13,069 --> 00:41:14,904
THE LITERATURE ON PERIMENOPAUSAL

1141
00:41:14,904 --> 00:41:15,872
DEPRESSION, A LINK BETWEEN

1142
00:41:15,872 --> 00:41:17,874
PERHAPS AN EARLIER AGE OF

1143
00:41:17,874 --> 00:41:20,944
MENOPAUSE AND THE ONSET OF

1144
00:41:20,944 --> 00:41:21,244
DEPRESSION.

1145
00:41:21,244 --> 00:41:23,146
I ALWAYS INTERPRET IT AS A

1146
00:41:23,146 --> 00:41:24,781
POTENTIAL, THE EFFECTS OF STRESS

1147
00:41:24,781 --> 00:41:27,150
AND DEPRESSION THAT LED TO AN

1148
00:41:27,150 --> 00:41:29,585
EARLIER LOSS OF OVARIAN FUNCTION

1149
00:41:29,585 --> 00:41:31,054
BUT THIS DATA WE WOULD HAVE TO

1150
00:41:31,054 --> 00:41:32,121
KRE TINS CONSIDER THAT OR I

1151
00:41:32,121 --> 00:41:33,957
WOULD HAVE TO KRE TINS OCCUR

1152
00:41:33,957 --> 00:41:36,726
THAT AND IT MAY ACTUALLY BE AN

1153
00:41:36,726 --> 00:41:38,494
UNDERLYING RISK FOR BOTH

1154
00:41:38,494 --> 00:41:39,662
PERIMENOPAUSAL DEPRESSION AND AN

1155
00:41:39,662 --> 00:41:41,864
EARLIER ONSET OF THE MENOPAUSE

1156
00:41:41,864 --> 00:41:44,734
IN SOME WOMEN EMPLOY SO, OVERALL

1157
00:41:44,734 --> 00:41:53,009
THEN TO END, WE ARE WORKING ON

1158
00:41:53,009 --> 00:41:56,179
THIS TYPE OF STUDY DESIGNS AND

1159
00:41:56,179 --> 00:41:57,814
TO BETTER UNDERSTAND THE EFFORT

1160
00:41:57,814 --> 00:42:03,419
OF THESE BIOLOGY CONDITIONS DITD

1161
00:42:03,419 --> 00:42:04,587
UNDERSTANDING WHY IN SOME WOMEN

1162
00:42:04,587 --> 00:42:09,892
THIS SEEMS TO BE A NORMAL CHANGE

1163
00:42:09,892 --> 00:42:10,960
OF OVARIAN FUNCTION CAN TRIGGER

1164
00:42:10,960 --> 00:42:12,362
THIS MOOD STATE AND HOPEFULLY

1165
00:42:12,362 --> 00:42:13,930
THAT WILL DEVELOP NEW TREATMENTS

1166
00:42:13,930 --> 00:42:16,432
AND HAVE A DIFFERENT MORE

1167
00:42:16,432 --> 00:42:17,867
FOCUSED TARGET AND A DIFFERENT

1168
00:42:17,867 --> 00:42:19,936
SAFETY PROFILE IN ALL OF THESE

1169
00:42:19,936 --> 00:42:22,372
CONDITIONS AND HOPEFULLY SOME OF

1170
00:42:22,372 --> 00:42:24,207
OUR INVITRO STUDIES WILL

1171
00:42:24,207 --> 00:42:26,376
IDENTIFY MARKERS OF RISK OR

1172
00:42:26,376 --> 00:42:26,909
POTENTIALLY LEAD TO SOME

1173
00:42:26,909 --> 00:42:31,147
TREATMENTS THAT MAY BE MORE

1174
00:42:31,147 --> 00:42:33,850
NOVEL AND ALTERNATIVE AT LEAST

1175
00:42:33,850 --> 00:42:35,651
FOR WOMEN WITH THIS STANDARD

1176
00:42:35,651 --> 00:42:36,452
HORMONE THERAPY EMPLOY WITH THAT

1177
00:42:36,452 --> 00:42:39,122
IN MIND I WANT TO ACKNOWLEDGE

1178
00:42:39,122 --> 00:42:41,491
PEOPLE IN MY GROUP, SARAH

1179
00:42:41,491 --> 00:42:42,992
SPECTER, THE NURSE PRACTITIONER

1180
00:42:42,992 --> 00:42:44,927
IN THE GROUP, [INDISCERNIBLE]

1181
00:42:44,927 --> 00:42:48,364
WHO IS MORE FOCUSED ON OUR

1182
00:42:48,364 --> 00:42:49,499
PREMENSTRUAL DYSPHORIC STUDIES

1183
00:42:49,499 --> 00:42:52,235
BUT RUNS OUR LARGE CUMBERSOME

1184
00:42:52,235 --> 00:42:56,773
AND BEAR LIKE PUBERTY STUDY.

1185
00:42:56,773 --> 00:42:59,275
SARAH RUDZINSKAS, I MENTIONED,

1186
00:42:59,275 --> 00:43:06,382
AS WELL AS CONSTRANS ZAU, I WANT

1187
00:43:06,382 --> 00:43:08,885
TO MENTION PAUL WAKIM, WHILE HE

1188
00:43:08,885 --> 00:43:12,722
WAS HERE AND NOW XIAOBAI, LI,

1189
00:43:12,722 --> 00:43:14,724
WHO IS NOW FITTING US IN WITH

1190
00:43:14,724 --> 00:43:17,560
THEIR NORMAL DUTIES TO BE

1191
00:43:17,560 --> 00:43:18,194
STATISTICAL CONSULTANTS.

1192
00:43:18,194 --> 00:43:24,600
FINALLY SOME OF MY LONGEST

1193
00:43:24,600 --> 00:43:25,868
STANDING COLLABORATORS, KAREN

1194
00:43:25,868 --> 00:43:31,908
BERM AN AT NIH, LINNET NEEMAN

1195
00:43:31,908 --> 00:43:33,676
WHO HAS BEEN INVOLVED IN THESE

1196
00:43:33,676 --> 00:43:35,511
STUDIES, DAVID CANNED WHAT AT

1197
00:43:35,511 --> 00:43:40,216
UNC AND THEN DAVID GOLDMAN

1198
00:43:40,216 --> 00:43:41,384
RUNNING OUR COLLABORATION WITH

1199
00:43:41,384 --> 00:43:44,654
OUR MOLECULAR STUDIES SO WITH

1200
00:43:44,654 --> 00:43:54,030
THAT WE CAN, ALL 10 OF YOU CAN

1201
00:43:54,030 --> 00:43:54,230
CLAP.

1202
00:43:54,230 --> 00:44:01,804
[ APPLAUSE ]

1203
00:44:01,804 --> 00:44:04,340
NHI, I'M [INDISCERNIBLE] I'M A

1204
00:44:04,340 --> 00:44:07,677
NEW CLINICAL FELLOW FOR CARLOS

1205
00:44:07,677 --> 00:44:09,045
[INDISCERNIBLE], WE'RE STUDYING

1206
00:44:09,045 --> 00:44:10,480
RESISTANCE TO DEPRESSION AND

1207
00:44:10,480 --> 00:44:11,981
BIOMARKERS SO FAR HAVE BEEN

1208
00:44:11,981 --> 00:44:14,617
FOCUSED ON THE GLUTAMATE SYSTEM,

1209
00:44:14,617 --> 00:44:16,152
MY PROJECT IN THAT LAB, WE'RE

1210
00:44:16,152 --> 00:44:19,222
BEGINNING TO ELECTRIC AT

1211
00:44:19,222 --> 00:44:21,190
NEUROSTEROIDS AND MYSELF, VERY

1212
00:44:21,190 --> 00:44:24,127
INTERESTED IN NEUROPEPTIDE

1213
00:44:24,127 --> 00:44:25,161
SPECIFICALLY, VASE O SUPPRESS

1214
00:44:25,161 --> 00:44:26,129
EVALUATION PROCESS AND OXYTOCIN,

1215
00:44:26,129 --> 00:44:27,897
AND FROM THE LITERATURE REVIEW,

1216
00:44:27,897 --> 00:44:31,801
I'VE DONE SO FAR, IT SEEMS LIKE,

1217
00:44:31,801 --> 00:44:33,269
WELLOXYITOSEIN IS HARD TO

1218
00:44:33,269 --> 00:44:37,440
MEASURE AND ALSO KIND OF HARD TO

1219
00:44:37,440 --> 00:44:37,640
GIVE.

1220
00:44:37,640 --> 00:44:40,276
VASE O PRESS ANT IS VERY RELATED

1221
00:44:40,276 --> 00:44:46,549
TOOXYITOSEIN BUT LOOKING AT

1222
00:44:46,549 --> 00:44:48,484
THAT, AS AOXYITOSEIN AND

1223
00:44:48,484 --> 00:44:52,021
[INDISCERNIBLE] AS A YING AND

1224
00:44:52,021 --> 00:44:53,489
YANG SYSTEM, AND MY

1225
00:44:53,489 --> 00:44:54,891
UNDERSTANDING IS THERE'S A LOT

1226
00:44:54,891 --> 00:44:57,894
OF SEX DNCHS IN HOW IT AFFECTS

1227
00:44:57,894 --> 00:44:58,628
DEPRSESSIVE SYMPTOMS AMONG

1228
00:44:58,628 --> 00:45:02,064
OTHERS AND I'M WONDERING, DO YOU

1229
00:45:02,064 --> 00:45:03,566
HAVE ANY SUGGESTIONS ON LOOKING

1230
00:45:03,566 --> 00:45:05,168
AT THE INTERSECTION OF

1231
00:45:05,168 --> 00:45:06,269
NEUROSTERIES LIKE YOU'VE DONE

1232
00:45:06,269 --> 00:45:10,139
AND NEUROPEPTIDES AND IF YOU

1233
00:45:10,139 --> 00:45:11,174
HAVE ANY WHYEDS?

1234
00:45:11,174 --> 00:45:12,341
NYEAH, VERY GOOD QUESTION.

1235
00:45:12,341 --> 00:45:17,113
INTERESTING THAT YOU'RE WORKING

1236
00:45:17,113 --> 00:45:17,747
ON THAT.

1237
00:45:17,747 --> 00:45:20,383
YES, SO THERE ARE SEVERAL WELL

1238
00:45:20,383 --> 00:45:21,450
DOCUMMED SEX DIFFERENCES BOTH IN

1239
00:45:21,450 --> 00:45:23,986
TERMS OF THE WIRING AND THE IRPT

1240
00:45:23,986 --> 00:45:26,322
ACTIONS OF KIND OF NEUROSTEROIDS

1241
00:45:26,322 --> 00:45:30,626
AND PEPTIDES, WHEN I STAY

1242
00:45:30,626 --> 00:45:32,428
NEUROSTEROIDS, I SAY ESTROGEN IS

1243
00:45:32,428 --> 00:45:33,329
NEUROACTIVE AND MAY ACTUALLY BE

1244
00:45:33,329 --> 00:45:38,668
MADE IN THE BRAIN JUST LIKE, THE

1245
00:45:38,668 --> 00:45:42,738
CLASSIC NEUROSTEROIDS THAT PAUL

1246
00:45:42,738 --> 00:45:44,040
[INDISCERNIBLE] DESCRIBED AS

1247
00:45:44,040 --> 00:45:44,774
METABOLITES OF PROGESTERONE IN

1248
00:45:44,774 --> 00:45:47,009
THE BRAIN OR AT LATEST ALL THE

1249
00:45:47,009 --> 00:45:48,244
SYNTHETIC ENZYMES ARE REQUIRED

1250
00:45:48,244 --> 00:45:49,345
AND PRESENT AND HAVE BEEN

1251
00:45:49,345 --> 00:45:50,413
IDENTIFIED IN THE BRAIN AND

1252
00:45:50,413 --> 00:45:56,919
CERTAIN LYE, I THINK IN MANY OF

1253
00:45:56,919 --> 00:45:59,855
THE SYSTEMS, PARTICULARLY IN THE

1254
00:45:59,855 --> 00:46:04,327
SOCIAL MODELS WITH THE VOLES,

1255
00:46:04,327 --> 00:46:05,962
TOM [INDISCERNIBLE]'S WORK AND

1256
00:46:05,962 --> 00:46:08,164
YOUNG'S WORK, THE WIRING OF

1257
00:46:08,164 --> 00:46:10,800
ESTRO GENRE SEPTORSORS BOTH ER

1258
00:46:10,800 --> 00:46:14,003
ALPHA AND ER BETA AS TO THE

1259
00:46:14,003 --> 00:46:16,839
REGULATION OF OXYTOCIN AND BASAL

1260
00:46:16,839 --> 00:46:22,144
DEPRESS ANT LOOK AT THE MODEL

1261
00:46:22,144 --> 00:46:24,280
FOR HOW THOSE MAY INTERACT AND

1262
00:46:24,280 --> 00:46:25,348
THE VARIABILITY THAT MAY OCCUR

1263
00:46:25,348 --> 00:46:26,482
IN THEM.

1264
00:46:26,482 --> 00:46:28,584
AS YOU SAID, THEY'RE

1265
00:46:28,584 --> 00:46:29,318
PROBLEMATIC, THEY'RE EASIER TO

1266
00:46:29,318 --> 00:46:31,687
MEASURE THAN THEY USED TO BE 20

1267
00:46:31,687 --> 00:46:32,755
YEARS AGO BUT THEIR PROBLEM WITH

1268
00:46:32,755 --> 00:46:38,527
HOW THEY GET INTO THE BRAIN,

1269
00:46:38,527 --> 00:46:39,929
WHERE THEY INTERACT, I THINK IN

1270
00:46:39,929 --> 00:46:42,431
SOME OF THE ANIMAL STUDIES, IT'S

1271
00:46:42,431 --> 00:46:45,334
CLEAR IF YOU GIVE VASO-PRESSIN

1272
00:46:45,334 --> 00:46:48,504
IN FEMALES THERE WILL BE KIND OF

1273
00:46:48,504 --> 00:46:52,908
A FRIEND AND BEFRIEND ACTION

1274
00:46:52,908 --> 00:46:55,845
WHEREAS, YOU GIVE IT TO MALES

1275
00:46:55,845 --> 00:46:57,947
THEY GET MORE DEFENSIVE AND MORE

1276
00:46:57,947 --> 00:46:59,382
TERRITORIAL.

1277
00:46:59,382 --> 00:47:00,783
SO THERE'S WONDERFUL SEXER

1278
00:47:00,783 --> 00:47:04,720
DIFFERENCES AND BEHAVIOR, AND

1279
00:47:04,720 --> 00:47:06,555
SEX DIFFERENCES IN BRAIN, IT'S

1280
00:47:06,555 --> 00:47:09,825
JUST IT'S KIND OF LIKE

1281
00:47:09,825 --> 00:47:10,760
[INDISCERNIBLE] MYTH THAT

1282
00:47:10,760 --> 00:47:12,762
THERE'S SO MANY CHOICES IT

1283
00:47:12,762 --> 00:47:14,497
STARTS GETTING VERY COMPLICATED

1284
00:47:14,497 --> 00:47:15,698
BUT WOULD BE HAPPY TO TALK WITH

1285
00:47:15,698 --> 00:47:26,142
YOU AND CARLOS ABOUT THIS.

1286
00:47:28,144 --> 00:47:29,045
>> THANK YOU DR. SCHMIDT
FOR

1287
00:47:29,045 --> 00:47:30,513
SHARING YOUR WORK AND INSIGHTS

1288
00:47:30,513 --> 00:47:31,714
ON THIS VERY IMPORTANT PROBLEM.

1289
00:47:31,714 --> 00:47:33,416
WE DO HAVE A COUPLE QUESTIONS

1290
00:47:33,416 --> 00:47:36,185
THAT CAME IN FROM OUR VIDEOCAST

1291
00:47:36,185 --> 00:47:38,354
VIEWERS, 1 IS HOW DOES ANOREXIA

1292
00:47:38,354 --> 00:47:40,589
IN A TIME OF PERIMENOPAUSE

1293
00:47:40,589 --> 00:47:45,227
AFFECT THE HORMONE LEVELS IN

1294
00:47:45,227 --> 00:47:46,162
DEPRESSION?

1295
00:47:46,162 --> 00:47:47,396
>> GOOD QUESTION.

1296
00:47:47,396 --> 00:47:51,500
WHEN I WAS IN TRIAL, I WORKED A

1297
00:47:51,500 --> 00:47:53,135
FAIR AMOUNT BECAUSE THERE WAS A

1298
00:47:53,135 --> 00:47:55,571
BIG PROGRAM ON EATING DISORDERS,

1299
00:47:55,571 --> 00:47:59,742
SO I THINK THE MAIN WORK ON THAT

1300
00:47:59,742 --> 00:48:01,644
EITHER IN SAN DIEGO OR IN

1301
00:48:01,644 --> 00:48:04,580
HARVARD, I DON'T THINK ANYBODY'S

1302
00:48:04,580 --> 00:48:07,249
EVER LOOKED AT THE, WHEREVER YOU

1303
00:48:07,249 --> 00:48:09,819
ARE, SORRY, I KEEP LOOKING AT

1304
00:48:09,819 --> 00:48:09,985
YOU.

1305
00:48:09,985 --> 00:48:10,486
>> IT'S OKAY.

1306
00:48:10,486 --> 00:48:13,322
>> I DON'T KNOW IF
ANYBODY'S

1307
00:48:13,322 --> 00:48:16,692
LOOKED AT WHETHER OR FOLLOWED

1308
00:48:16,692 --> 00:48:19,328
WOMEN WITH OR MEN WITH EATING

1309
00:48:19,328 --> 00:48:21,464
DISORDERS THAT IS A GO THROUGH

1310
00:48:21,464 --> 00:48:23,966
THE MENOPAUSE TRANSITION.

1311
00:48:23,966 --> 00:48:27,002
I THINK THE--YOU KNOW IT'S

1312
00:48:27,002 --> 00:48:30,072
SYRUPLY THE ENDOCRINE EFFECTS OF

1313
00:48:30,072 --> 00:48:33,676
STARVATION ARE VERY PROMINENT

1314
00:48:33,676 --> 00:48:37,780
AND CAN INDUCE AMENERRIA LIKE

1315
00:48:37,780 --> 00:48:38,814
SARAH BURGER'S WORK AND OTHER

1316
00:48:38,814 --> 00:48:40,249
VERY LONGS HAVE SHOWN THAT WHEN

1317
00:48:40,249 --> 00:48:45,087
THERE'S A CERTAIN THRESHOLD OF

1318
00:48:45,087 --> 00:48:47,957
CALORIES INTAKE BELOW WHICH THE

1319
00:48:47,957 --> 00:48:50,826
REPRODUCTIVE ACTS SHUTS DOWN,

1320
00:48:50,826 --> 00:48:52,161
IT'S CONSIDERABLY VARIABLE

1321
00:48:52,161 --> 00:48:54,130
ACROSS WOMEN BUT INN REXIO THAT

1322
00:48:54,130 --> 00:48:56,165
IS 1 OF THE GREAT COMPLICATIONS

1323
00:48:56,165 --> 00:49:03,139
AND WOMEN OR GIRLS WITH

1324
00:49:03,139 --> 00:49:03,839
ANOREXIA, THAT OFTEN PREVENT

1325
00:49:03,839 --> 00:49:05,274
THEM FROM GETTING INTO THE

1326
00:49:05,274 --> 00:49:07,176
PUBERTY EXPE 1 OF THE PROBLEMS

1327
00:49:07,176 --> 00:49:10,146
WE USED TO FACE INTRADA IS WHEN

1328
00:49:10,146 --> 00:49:11,781
THOSE GIRLS START GETTING REFED

1329
00:49:11,781 --> 00:49:13,649
AND THEIR AXIS STARTS

1330
00:49:13,649 --> 00:49:15,050
REACTIVATING THEN THEY START

1331
00:49:15,050 --> 00:49:18,621
MAKING ESTROIEN AND THEIR BONES

1332
00:49:18,621 --> 00:49:19,955
SURDENLY START CLOSING AND THEY

1333
00:49:19,955 --> 00:49:22,525
MAY BE AT REFRESHING FOR SHORT

1334
00:49:22,525 --> 00:49:24,360
STARTY STATURE SO WE WOULD HAVE

1335
00:49:24,360 --> 00:49:25,961
TO PROLONG SUPPRESSION OF

1336
00:49:25,961 --> 00:49:27,963
PUBERTY IN THEM WHILE THEY WERE

1337
00:49:27,963 --> 00:49:29,932
REFEEDING AND LET THINGS HAPPEN

1338
00:49:29,932 --> 00:49:31,100
MORE TBRADDUALLY.

1339
00:49:31,100 --> 00:49:32,468
THERE'S ALSO BEEN CANNED WHAT'S

1340
00:49:32,468 --> 00:49:34,770
GROUP UP IN HARVARD DEMON

1341
00:49:34,770 --> 00:49:38,307
TRAITED RELEVANCE OF SOME

1342
00:49:38,307 --> 00:49:38,874
ANDROGENS PARTICULARLY

1343
00:49:38,874 --> 00:49:40,042
TESTOSTERONE IN THAT GROUP.

1344
00:49:40,042 --> 00:49:42,611
TO BE HONEST I THINK A LOT OF

1345
00:49:42,611 --> 00:49:44,413
WOMEN WITH EATING DISORDERS GET

1346
00:49:44,413 --> 00:49:46,749
LOST AS THEY AGE AND I THINK

1347
00:49:46,749 --> 00:49:48,584
THAT WHAT HAPPENS, THERE USED TO

1348
00:49:48,584 --> 00:49:50,886
BE A SENSE THAT THESE THINGS

1349
00:49:50,886 --> 00:49:51,821
WOULD JUST BECOME CHRONIC AND

1350
00:49:51,821 --> 00:49:54,023
THE WOMAN IF THEY SURVIVED TO

1351
00:49:54,023 --> 00:49:57,593
THAT AIM, THEY WOULD HAVE FOUND

1352
00:49:57,593 --> 00:50:00,796
BALANCE BETWEEN THEIR EATING

1353
00:50:00,796 --> 00:50:02,998
DISORDER AND KIND OF STAYING

1354
00:50:02,998 --> 00:50:03,199
ALIVE.

1355
00:50:03,199 --> 00:50:08,037
SOIME NOT SURE WHAT HAPPENS, TO

1356
00:50:08,037 --> 00:50:09,171
BE HONEST.

1357
00:50:09,171 --> 00:50:09,472
>> GREAT.

1358
00:50:09,472 --> 00:50:10,239
THANK YOU NIT'S PROBABLY NOT

1359
00:50:10,239 --> 00:50:11,640
GOING TO HELP IF THEY STOP

1360
00:50:11,640 --> 00:50:13,843
EATING AS THEY GO THROUGH THE

1361
00:50:13,843 --> 00:50:16,145
MENOPAUSE NAS A PEDIATRIC

1362
00:50:16,145 --> 00:50:17,279
CARDIOLOGIST, I WOULD PROBABLY

1363
00:50:17,279 --> 00:50:17,913
APREWITH THAT.

1364
00:50:17,913 --> 00:50:20,082
ANOTHER QUESTION THAT CAME IN IS

1365
00:50:20,082 --> 00:50:22,184
HOW DOES SURGICAL MENOPAUSE I.

1366
00:50:22,184 --> 00:50:24,186
E. HYSTERECTOMY ALTER THE

1367
00:50:24,186 --> 00:50:25,354
INFLMATORY RESPONSE OF DECLINE

1368
00:50:25,354 --> 00:50:27,790
IN HORMONES FROM THE RAPID

1369
00:50:27,790 --> 00:50:30,326
INDUCTION COMPARED TO

1370
00:50:30,326 --> 00:50:31,694
QUOTE-UNQUOTE NORMAL BIOLOGICAL

1371
00:50:31,694 --> 00:50:33,062
PROGRESSION OVER TIME?

1372
00:50:33,062 --> 00:50:34,597
>> YES, SO, IT MIMICS WHAT
A

1373
00:50:34,597 --> 00:50:36,565
WOMAN GOES THROUGH, THE NATURAL

1374
00:50:36,565 --> 00:50:39,869
MENOPAUSE IN MANY WAYS AS THE

1375
00:50:39,869 --> 00:50:41,103
QUESTIONER ASKS OR SUGGIESTED

1376
00:50:41,103 --> 00:50:44,507
IT'S MUCH MORE RAPID, WITH THE

1377
00:50:44,507 --> 00:50:49,111
OVARIES REMOVED YOU ALSO LOSE A

1378
00:50:49,111 --> 00:50:50,846
PORTION OF TESTOSTERONE

1379
00:50:50,846 --> 00:50:52,815
PRODUCTION THAT IS PRESENT BY

1380
00:50:52,815 --> 00:50:55,584
THE OVAFYS, IT'S A LOT OF

1381
00:50:55,584 --> 00:50:56,652
DENOAFY TESTOSTERONE OR

1382
00:50:56,652 --> 00:50:59,622
CONVERSION OF HORMONES LIKE

1383
00:50:59,622 --> 00:51:00,723
ADRENAL ANDROGENS INTO

1384
00:51:00,723 --> 00:51:01,056
TESTOSTERONE.

1385
00:51:01,056 --> 00:51:07,696
SO THAT IS AN ARK DITIONAL

1386
00:51:07,696 --> 00:51:08,831
ELEMENT.

1387
00:51:08,831 --> 00:51:09,965
THE EPIDEMIOLOGY, AND AND THERE

1388
00:51:09,965 --> 00:51:13,836
HAS BEEN BOTH STUDIES SUGGESTING

1389
00:51:13,836 --> 00:51:15,004
THERE CAN BE SIMILAR NATIVE

1390
00:51:15,004 --> 00:51:19,875
EFFECTS ON MOOD AND COGNITION

1391
00:51:19,875 --> 00:51:20,676
BUT THERE ALSO HAS BEEN SOME

1392
00:51:20,676 --> 00:51:21,911
CENTER FOR EXCELLENCE ON AGINGS

1393
00:51:21,911 --> 00:51:25,948
WHETHER IT'S A SURGICAL

1394
00:51:25,948 --> 00:51:26,315
[INDISCERNIBLE].

1395
00:51:26,315 --> 00:51:27,149
AND MORE RECENT PAPERS IN

1396
00:51:27,149 --> 00:51:32,922
SCIENCE OR THE LAST COUPLE OF

1397
00:51:32,922 --> 00:51:34,957
YEARS SUGGESTING OVARIAN

1398
00:51:34,957 --> 00:51:35,991
SUPPRESS OR GONE ADAL

1399
00:51:35,991 --> 00:51:37,960
SUPPRESSION MAY HAVE BENEFICIAL

1400
00:51:37,960 --> 00:51:38,627
EFFECTS ON COGNITIVE FUNCTION

1401
00:51:38,627 --> 00:51:42,765
DOWN THE ROAD SO THE GAIP IS

1402
00:51:42,765 --> 00:51:46,402
SOMETHING THAT THERE'S A MIXED

1403
00:51:46,402 --> 00:51:54,743
COHORT IN TERMS OF FOR A THEY

1404
00:51:54,743 --> 00:51:56,712
MAY CONTRIBUTE TO MOOD OR

1405
00:51:56,712 --> 00:51:59,214
COGNITIVE CHANGES SO IT'S LESS

1406
00:51:59,214 --> 00:52:05,087
CLEAR I THINK THAN KIND OF SOME

1407
00:52:05,087 --> 00:52:05,821
OF THESE STUDIES.

1408
00:52:05,821 --> 00:52:07,957
>> NEXT JUST A COMMENT,
THANK

1409
00:52:07,957 --> 00:52:11,260
YOU DR. SCHMIDT FOR SUCH A

1410
00:52:11,260 --> 00:52:11,827
THOUGHT-PROVOKING HELPFUL

1411
00:52:11,827 --> 00:52:13,228
INFORMATION, I LOOK FORWARD

1412
00:52:13,228 --> 00:52:15,431
ABOUT READING MORE FOR THIS

1413
00:52:15,431 --> 00:52:15,931
CLINICAL RESEARCH AREA.

1414
00:52:15,931 --> 00:52:25,774
>> THANK YOU VERY MUCH.

1415
00:52:25,774 --> 00:52:26,041
>> YEAH.

1416
00:52:26,041 --> 00:52:30,112
>> JUST 1 COMMENT SO ROANA
LAB

1417
00:52:30,112 --> 00:52:32,748
HERE AT THE NIH HAS A VERY

1418
00:52:32,748 --> 00:52:34,917
INTERESTING STORY THAT SOMEBODY

1419
00:52:34,917 --> 00:52:37,886
SHE WILL SHARE RELATED TO ER

1420
00:52:37,886 --> 00:52:39,388
BETA AND AGE RELATED HEARING

1421
00:52:39,388 --> 00:52:43,492
LOSS IN WOMEN, SO THAT'S

1422
00:52:43,492 --> 00:52:44,526
SOMETHING THAT THEY'RE VERY

1423
00:52:44,526 --> 00:52:45,694
INVESTED IN AND WE'RE WORKING

1424
00:52:45,694 --> 00:52:47,696
WITH THEM TO TRY TO SEE IF WE

1425
00:52:47,696 --> 00:52:49,098
CAN FIND SOME OF OUR COMPOUND TO

1426
00:52:49,098 --> 00:52:53,902
LOOK AT IN THAT GROUP. 

1427
00:52:53,902 --> 00:52:55,404
>> I WAS GOING TO ASK A
QUESTION

1428
00:52:55,404 --> 00:52:58,374
ABOUT KEEPING THESE WOMEN IN THE

1429
00:52:58,374 --> 00:52:59,108
TRIAL DESPITE APPARENT

1430
00:52:59,108 --> 00:53:00,376
DEPRESSION AND HOW MUCH WORK IT

1431
00:53:00,376 --> 00:53:02,144
IS TO FOLLOW PATIENTS

1432
00:53:02,144 --> 00:53:04,446
LONGITUDINALLY IN THESE TYPES OF

1433
00:53:04,446 --> 00:53:06,682
TRIALS? 

1434
00:53:06,682 --> 00:53:11,520
>> YES, YES, WELL IT'S YOU
CAN

1435
00:53:11,520 --> 00:53:14,323
ASK XIOMING ABOUT IT, IT'S WORSE

1436
00:53:14,323 --> 00:53:15,758
FROM THE PEDIATRIC END

1437
00:53:15,758 --> 00:53:17,559
APPARENTLY, I TRY TO STAY AWAY

1438
00:53:17,559 --> 00:53:19,662
FROM THAT GROUP, I LIKE TO HEAR

1439
00:53:19,662 --> 00:53:22,331
REPORTS WHEN STAFF ARE

1440
00:53:22,331 --> 00:53:24,033
MISBEHAVING THAT'S MY MAIN ROLE

1441
00:53:24,033 --> 00:53:26,602
BUT OTHERWISE IT'S HANDS-OFF.

1442
00:53:26,602 --> 00:53:28,404
BUT IN PERIMENOPAUSE, THE WOMEN

1443
00:53:28,404 --> 00:53:29,371
WHO DEVELOPED DEPRESSION, IT'S

1444
00:53:29,371 --> 00:53:30,539
OCCURRING IN A CONTEXT OF A

1445
00:53:30,539 --> 00:53:33,575
RELATIONSHIP, SO IN CONTRAST TO

1446
00:53:33,575 --> 00:53:36,345
WHAT MANY PEOPLE THINK ABOUT THE

1447
00:53:36,345 --> 00:53:38,347
RESEARCH, WE'RE--YOU KNOW

1448
00:53:38,347 --> 00:53:39,314
FOLLOWING THEM VERY CLOSE AND WE

1449
00:53:39,314 --> 00:53:41,517
TAKE THE TIME TO DEVELOP THESE

1450
00:53:41,517 --> 00:53:45,888
RELATIONSHIPS AND THEIR VERY

1451
00:53:45,888 --> 00:53:49,191
CONNECTED TO THE STAFF, ALL 5 OR

1452
00:53:49,191 --> 00:53:50,726
6 THAT ARE HERE SO THEY'LL TALK

1453
00:53:50,726 --> 00:53:52,795
TO US AND I THINK WE'LL WORK

1454
00:53:52,795 --> 00:53:54,763
WITH THEM AS TO WHETHER THIS IS

1455
00:53:54,763 --> 00:53:55,564
SOMETHING THAT THEY FEEL THEY

1456
00:53:55,564 --> 00:53:57,566
WOULD LIKE TO COPE WITH, MANY OF

1457
00:53:57,566 --> 00:54:01,737
THESE DEPRESSIONS WERE

1458
00:54:01,737 --> 00:54:03,138
IDENTIFIED EARLY ON AND WERE

1459
00:54:03,138 --> 00:54:05,407
MORE MINOR WHICH WE KNOW CAN

1460
00:54:05,407 --> 00:54:06,809
DEVELOP INTO MORE MAJOR

1461
00:54:06,809 --> 00:54:07,776
DEPRESSIONS, YOU KNOW THE POINT

1462
00:54:07,776 --> 00:54:09,178
WOULD BE THERE WOULD BE A LINE

1463
00:54:09,178 --> 00:54:10,345
WHERE THEY WOULD NOT FEEL

1464
00:54:10,345 --> 00:54:11,747
COMFORTABLE AND THEY WOULD BE

1465
00:54:11,747 --> 00:54:14,183
WANTING TREATMENT AND THEY WOULD

1466
00:54:14,183 --> 00:54:15,050
STOP THE STUDY.

1467
00:54:15,050 --> 00:54:16,685
AND WE WOULD JUST FOLLOW THEM

1468
00:54:16,685 --> 00:54:18,954
MAYBE TO FIND OUT WHEN THEIR

1469
00:54:18,954 --> 00:54:19,888
LAST MENSTRUAL PERIOD WAS AND

1470
00:54:19,888 --> 00:54:22,891
THERE'S A NUMBER OF THOSE WOMEN

1471
00:54:22,891 --> 00:54:23,792
THAT WERE THERE.

1472
00:54:23,792 --> 00:54:25,227
OTHERS, YOU KNOW, WE WERE

1473
00:54:25,227 --> 00:54:26,729
WILLING TO GO WITH WHAT THEY

1474
00:54:26,729 --> 00:54:28,931
WANTED TO DO AND THEY FELT THAT

1475
00:54:28,931 --> 00:54:32,000
THEY WERE COPING FINE.  THIS AN

1476
00:54:32,000 --> 00:54:32,935
OUTPATIENT DEPRESSION AND THEY

1477
00:54:32,935 --> 00:54:35,437
WANTED TO SEE WHETHER IT WOULD

1478
00:54:35,437 --> 00:54:36,972
REMIT ON ITS OWN AND THEY WOULD

1479
00:54:36,972 --> 00:54:42,044
CARRY ON AND SOME OF THEM DID,

1480
00:54:42,044 --> 00:54:42,644
OTHERS DIDN'T.

1481
00:54:42,644 --> 00:54:44,213
AND THERE'S A LOT OF MEDICAL

1482
00:54:44,213 --> 00:54:45,147
ILLNESS THAT HAPPENS AT THIS

1483
00:54:45,147 --> 00:54:46,682
TIME AND THOSE WOMEN WERE

1484
00:54:46,682 --> 00:54:47,983
EXCLUDED FROM THE DATA ANALYSIS,

1485
00:54:47,983 --> 00:54:52,187
BUT YOU KNOW A LOT OF MEDICAL

1486
00:54:52,187 --> 00:54:54,890
THINGS HAPPEN YOU KNOW KIND OF

1487
00:54:54,890 --> 00:54:58,193
TRIBUTE TO DEPRESSION BUT THAT

1488
00:54:58,193 --> 00:54:59,128
WE COULDN'T SOLELY ACKNOWLEDGE

1489
00:54:59,128 --> 00:55:03,699
ITS LINK TO THE PERIMENOPAUSE.

1490
00:55:03,699 --> 00:55:05,667
BUT IN THE CLINIC WHEN WE SEE

1491
00:55:05,667 --> 00:55:07,035
THEM THIS OFTEN, THAT'S WHERE

1492
00:55:07,035 --> 00:55:09,838
EACH OF THEM IS LIKE A CASE

1493
00:55:09,838 --> 00:55:12,241
REPORT, PROGRESS NOTES AND WE

1494
00:55:12,241 --> 00:55:13,976
CAN LOOK BACK ON THAT AND SEE

1495
00:55:13,976 --> 00:55:17,045
WHAT WAS HAPPENING WITH EACH

1496
00:55:17,045 --> 00:55:17,813
INDIVIDUAL WOMAN.

1497
00:55:17,813 --> 00:55:19,348
AND THAT'S THE IMPORTANCE OF THE

1498
00:55:19,348 --> 00:55:20,916
ABILITY OF THESE LONGITUDINAL

1499
00:55:20,916 --> 00:55:23,786
STUDIES AT NIH BECAUSE IN AN

1500
00:55:23,786 --> 00:55:25,420
EPIDEMIOLOGIC STUDY, YOU KNOW,

1501
00:55:25,420 --> 00:55:26,822
THERE'S THE HUGE DATA COLLECTION

1502
00:55:26,822 --> 00:55:28,624
EFFORT THAT STANDS BETWEEN YOU

1503
00:55:28,624 --> 00:55:31,293
AND THE PATIENT AND SO THERE'S

1504
00:55:31,293 --> 00:55:33,462
CERTAIN NUANCE EVENTS OF THEIR

1505
00:55:33,462 --> 00:55:34,429
EXPERIENCE THAT DON'T GET

1506
00:55:34,429 --> 00:55:35,230
CAPTURED AND THE RELATIONSHIP IS

1507
00:55:35,230 --> 00:55:38,033
NOT THERE SO YOU MAY NOT

1508
00:55:38,033 --> 00:55:39,001
ACTUALLY HAVE CHANNELS OPEN TO

1509
00:55:39,001 --> 00:55:46,975
HEAR ABOUT SOME OF THESE THINGS.

1510
00:55:46,975 --> 00:55:50,913
SO ...

1511
00:55:50,913 --> 00:55:52,114
>> SO DR. SCHMIDT, MIGHT A
WOMAN

1512
00:55:52,114 --> 00:55:54,750
WHO HAS A HISTORY OF DEPRESSION

1513
00:55:54,750 --> 00:55:57,686
REQUEST HER GYNECOLOGIST OR PC P

1514
00:55:57,686 --> 00:56:01,390
REQUEST THEY MEASURE HER FSH IN

1515
00:56:01,390 --> 00:56:02,658
HER PERIMENOPAUSAL PERIOD IN.

1516
00:56:02,658 --> 00:56:04,693
>> YEAH, I THINK THE
CRITERIA,

1517
00:56:04,693 --> 00:56:08,330
THE STAGES OF REPROUCT DIDDIVE

1518
00:56:08,330 --> 00:56:10,399
ANALLING WORKSHOP, THEY RELY

1519
00:56:10,399 --> 00:56:12,267
LESS ON FSH AND INHIB THORSIN

1520
00:56:12,267 --> 00:56:13,569
ISSUE THE ASSAY IS GETTING

1521
00:56:13,569 --> 00:56:15,304
BETTER, I'M NOT SURE IT'S READY

1522
00:56:15,304 --> 00:56:17,739
FOR PRIME TIME BUT I THINK THE

1523
00:56:17,739 --> 00:56:19,007
MOST IMPORTANT CRITERIA WOULD BE

1524
00:56:19,007 --> 00:56:21,877
IF THEY ARE SKIPPING CYCLES OR

1525
00:56:21,877 --> 00:56:23,512
IF THEIR CYCLES HAVE CHANGED IN

1526
00:56:23,512 --> 00:56:23,846
LENGTH.

1527
00:56:23,846 --> 00:56:28,617
THEY TALK ABOUT A WEEK SHORTER

1528
00:56:28,617 --> 00:56:30,419
OR A WEEK LONGER, IF THERE'S A

1529
00:56:30,419 --> 00:56:33,789
CHANGE IN THE BLOODING PATTERN,

1530
00:56:33,789 --> 00:56:34,890
OFTEN PLEADING BECOME HEAVIER

1531
00:56:34,890 --> 00:56:38,093
DURING THIS TIME, PLUS OR MINUS

1532
00:56:38,093 --> 00:56:40,028
OTHERRICISM TOPS OF

1533
00:56:40,028 --> 00:56:41,496
INSUFFICIENCY, WHETHER IT'S

1534
00:56:41,496 --> 00:56:43,498
VAGINAL DRYNESS OR HOT FLASHES,

1535
00:56:43,498 --> 00:56:45,133
THEY NOT NEED TO CONFIRM THAT

1536
00:56:45,133 --> 00:56:46,335
BUT CERTAINLY HAD MANY WOMEN IN

1537
00:56:46,335 --> 00:56:49,504
THE CLIPPIC THEY HAVE HAD

1538
00:56:49,504 --> 00:56:52,174
MEASURES OF FSH, ESTRO DIAL, THE

1539
00:56:52,174 --> 00:56:53,242
ASSAYS FOR ESTRA-DIAL WHEN IT

1540
00:56:53,242 --> 00:56:54,743
GERONTOLOGYSTSS LOW ARE NOT VERY

1541
00:56:54,743 --> 00:56:56,044
RELIABLE UNLESS YOUR USING

1542
00:56:56,044 --> 00:56:58,213
THINGS LIKE MASS SPEC, SO MANY

1543
00:56:58,213 --> 00:56:59,181
GYNECOLOGISTS WILL DO THAT BUT

1544
00:56:59,181 --> 00:57:00,716
MANY OF THEM ALSO WILL FEEL

1545
00:57:00,716 --> 00:57:01,984
COMFORTABLE JUST BY THE WOMAN'S

1546
00:57:01,984 --> 00:57:04,052
AGE AND SOME OF THE OTHER

1547
00:57:04,052 --> 00:57:05,787
SYMPTOMS OF THEIR MENSTRUAL

1548
00:57:05,787 --> 00:57:08,924
CYCLE HISTORY THIS THEY DON'T

1549
00:57:08,924 --> 00:57:10,392
REQUIRE. 

1550
00:57:10,392 --> 00:57:11,727
HORMONE MEASURES.

1551
00:57:11,727 --> 00:57:13,362
>> WE MAYBE HAVE TIME FOR
1 LAST

1552
00:57:13,362 --> 00:57:13,629
QUESTION.

1553
00:57:13,629 --> 00:57:14,763
THIS WILL BE SHORT.

1554
00:57:14,763 --> 00:57:17,599
HAD MANY OF THE PATIENTS IN YOUR

1555
00:57:17,599 --> 00:57:19,234
STUDY SUFFERED FROM PTSD?

1556
00:57:19,234 --> 00:57:22,371
>> WELL IT'S SOMETHING
THAT

1557
00:57:22,371 --> 00:57:23,205
CONSTANCE IS LOOKING AT.

1558
00:57:23,205 --> 00:57:26,842
I THINK WE ARE LOOKING AT EARLY

1559
00:57:26,842 --> 00:57:27,743
LIFE TRAUMA.

1560
00:57:27,743 --> 00:57:33,248
SO I THINK THAT IS WHAT WE FELT

1561
00:57:33,248 --> 00:57:34,483
WAS IMPORTANT.

1562
00:57:34,483 --> 00:57:37,719
NONE OF THE MET CRITERIA ON THE

1563
00:57:37,719 --> 00:57:39,154
STRUCTURED DIAGNOSTIC INTERVIEW

1564
00:57:39,154 --> 00:57:41,623
FOR PTSD KIND OF BEFORE HAND, AT

1565
00:57:41,623 --> 00:57:43,158
LEAST NOT MANY OF THEM, BUT MANY

1566
00:57:43,158 --> 00:57:46,962
OF THEM DO HAVE AND THERE IS A

1567
00:57:46,962 --> 00:57:49,564
LITERATURE RELATED TO EARLY LIFE

1568
00:57:49,564 --> 00:57:53,969
STRESS WHICH IS A COMPLICATED

1569
00:57:53,969 --> 00:57:56,071
RELATIONSHIP WITH REPORTS OF

1570
00:57:56,071 --> 00:57:58,740
PTSD, BOTH IN TERMS OF

1571
00:57:58,740 --> 00:57:59,174
FALSE-NEGATIVES AND

1572
00:57:59,174 --> 00:58:00,542
FALSE-POSITIVES BUT WE HAVE THAT

1573
00:58:00,542 --> 00:58:03,578
INFORMATION AND WE WILL BE

1574
00:58:03,578 --> 00:58:04,346
LOOKING AT THAT.

1575
00:58:04,346 --> 00:58:06,715
BUT CERTAINLY IN WOMEN IN

1576
00:58:06,715 --> 00:58:08,951
GENERAL WHO PRESENT TO

1577
00:58:08,951 --> 00:58:09,985
BEHAVIORIAL HEALTH CLINICS,

1578
00:58:09,985 --> 00:58:12,054
THERE'S ABOUT A 60% OR HIGHER

1579
00:58:12,054 --> 00:58:16,391
RATE OF EARLY LIFE TRAUMA, SO, I

1580
00:58:16,391 --> 00:58:19,962
THINK THAT'S WHY PTSD IS NOT AN

1581
00:58:19,962 --> 00:58:21,697
UNCOMMON ANTISEEDENT TO A LOT OF

1582
00:58:21,697 --> 00:58:23,932
THESE CONDITIONS.

1583
00:58:23,932 --> 00:58:24,800
THANK YOU.

1584
00:58:24,800 --> 00:58:29,905
I THINK THAT REALLY IS IT.

1585
00:58:29,905 --> 00:58:40,182
THANK YOU.