Prechter Bipolar Research Program Faculty Meeting 2019

Prechter Faculty Meeting: Agenda

• Introductions • Overview of Prechter Program • Overview and vision of Precision Health • Three base questions – engagement /personal reviews / priorities

• New ideas discussions • Governance • Advisory board• ‘superuser’ / super participant projects

Prechter Program: History 

• Story of Heinz Prechter• Creative entrepreneur • Suicide 2001

• Family Established Fund• Moved to UM in 2005 • 2017: commitment of 5M in endowed funds

• Matching funds • Continued engagement in fund raising

Mission and Vision Statements 

• Our Mission:• The mission of the Heinz C. Prechter Bipolar Research Program is to discover the mechanisms that contribute to bipolar disorder, predict and improve outcomes, and develop effective, innovative treatments.

• Our Vision:• We are building a future where personalized and evidence‐based treatments for bipolar disorder will enable every individual with the illness to lead a healthy and productive life.

UM: Prechter Project origins 

• Began project in 2005 (IRB) approval date. • HUM0000606

• Logic:   large scale genetic projects were emerging. The Odds Ratios for each locus: modest (1.15)

• No projects focused on level of detail at phenotype level• The Prechter program would be complementary to large programs 

Academic Landscape Bipolar Disorder Genetics  ‐ 2005

• No genes associated with Bipolar Disorder• Appreciation that many genes were involved 

• Large collaboratives GWAS• Wide studies: many participants, limited data

• Few longitudinal studies in Bipolar disorder• Compare:  Framingham Heart Study (began 1948)• Deep studies: fewer participants, extensive data

Prechter Bipolar Research ProgramPrecision Health

Heinz C Prechter1942 – 2001

Clinic

University Community

Eligibility Screening

Ineligible Eligible

Initial Visit

DIGS InterviewNeuropsychological

Testing

Blood for Genetics & Biomarkers Questionnaires

Follow-up

Year 1: Neuropsychological Testing

Year 3: Phone check in

Year 2: LIFE Interview

Questionnaires every 2 months

Clinic

University Community

Eligibility Screening

Ineligible Eligible

Initial Visit

DIGS InterviewNeuropsychological

Testing

Blood for Genetics & Biomarkers Questionnaires

Follow-up

Year 1: Neuropsychological Testing

Year 3: Phone check in

Year 2: LIFE Interview

Questionnaires every 2 months

• Mechanisms – Predictive Modeling

• Longitudinal– Active engagement

• > 1300 Participants – 75% retention Entering Year 14

Longitudinal Study of Bipolar DisorderIdentify mechanisms & predictive outcomes patterns in bipolar disorder

January 2019

Total Enrolled:1304Current Participants: 926 (71%)Central Biorepository: 613Prechter Bipolar Genetics Repository: 2,088Data Sharing Agreements: 18Peer Reviewed publications: 92

0200400600800100012001400

Longitudinal Enrollment Status October 2018

Ontology: Disciplines & Pluralistic Relationship to Phenotype Class

Phenotype Classes (7)

Disciplines (10) 

– Disease– Neurocognitive– Temperament / Personality– Motivated Behavior– Life Story– Sleep / Circadian– Outcomes

Human Volunteer Participants 

Prechter Phenotype classes 

• Disease: • DIGS & LIFE

• Temperament / Personality• NEO PI‐R• BIS‐11 (Barret Impulsivity)• Buss‐Durkee Hostility• Brown Goodwin Aggression 

• Motivated Behavior• Fagerstrom• Audit‐R 

• Alcohol and substance use 

• Sleep & Circadian • PSQI (Pitt Sleep..) • MCTQ (Munich ..)• SPAQ (seasonal pattern assessment

Prechter Phenotype classes 

• Life Story/Experiences• LEOS (Life Events occur..• LEC (Life Events Checklist..• FACES II (Family Adapt..• CTQ (Childhood Trauma..• LFQ (Life Functioning • ECR (Experiences Close ..• Working Alliance Inventory 

• Clinical outcomes• PHQ9, ASRM, GAD7, SF12• YMRS, HAMD• C‐SSRS

• Neurocognitive Function• WAIS• CVLT• Rey‐Osterrieth• Facial Emotion Perception• Emotion Processing Test• Purdue Pegboard• Parametric Go/No Go• Stroop Color Word• Trail Making• Wisconsin Card Sort• Synonym Knowledge• Test of Memory Malingering

Dynamic Energy State

Mania Depression

Time

Bipolar Disorder: CoursePathology of Energy 

1 year

Mania Depression  anticipate change?  

Data types

• Course and outcomes 

• Illness patterns• Psychology• Neuropsychology• Acoustic patterns • Life Story • Behaviors• Circadian 

• Biological Mechanisms

• Cell Developmental Biology • Genetics• Pharmacology • Animal models• Cellular models 

• Missing Imaging • S. Taylor 

> 90 peer reviewed publications with scientists from 7 U‐M SchoolsUM experts: local network

Bipolar DATA Management Systems University of Michigan 

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** Potential Data sources

NDAR

Next UP….• “Superuser” project: increasing depth and detail at the individual level.

• Microbiome, metabolome, physiology• Imaging & electrophysiology• Health service utilizations patterns• Cellular & developmental modelling • Computational modeling 

• Goal is a Bipolar P01 in 3 years. 

Partnerships: InternalPharmacology / Cardiology / Computer Science & EngineeringCell Developmental Biology / Life Sciences Institute / MathematicsExternal: Weizmann Inst., U Oslo, Lebanon, U Penn, UIC, U Wisconsin

Network Acknowledgments 

• Prechter Bipolar Research Fund• Richard Tam Foundation• Department of Psychiatry• U‐M Depression Center• NIMH• MICHR / MTRAC• Woodworth Family • Supporters of the Prechter Program• Individual research participants and families

• Staff and Faculty members at the UM